The patient has a PSA >4 and a palpation with increased consistency, which implies the need for a transrectal ultrasound-guided biopsy to diagnose whether it is Benign Prostatic Hyperplasia or Prostate Cancer.

Faced with a 49-year-old man, asymptomatic, with a family history of a father who died of prostate cancer, who in a routine company control is identified a PSA (Prostate Specific Antigen) of 5.9 ng / ml, with a ratio of free PSA / total PSA of 11% and that a rectal examination shows increased consistency in the right prostatic lobe, what is the following clinical indication?

Suggest to the patient the performance of a transrectal ultrasound and prostate biopsy.

Initiate treatment with 5 alpha Reductase Inhibitors to reduce PSA levels by half.

Initiate combined treatment of LHRH analogues and antiandrogens.

Histopathology, pharmacotherapy, and predictors of prostatic malignancy in elderly male patients with raised prostate-specific antigen levels - A prospective study.

Prostate cancer is the second most common cancer among adult men in the world, and the diagnosis requires biopsy. Prostate-specific antigen (PSA) test along with digital rectal examination (DRE) increases the detection rate of prostate cancer than DRE alone. The objective of this study was to correlate serum PSA level with histopathological diagnosis, identify the predictors of malignancy, and describe the pharmacotherapy of patients with serum PSA levels >4 ng/ml. This was a hospital-based observational study done among patients who presented with lower urinary tract symptoms and PSA levels >4 ng/ml who were planned to undergo prostatic biopsy. DRE followed by transrectal ultrasound (TRUS) assessment and guided sextant (6-core) prostatic biopsy was performed. One hundred and four patients were screened and 87 were included. Nineteen patients were diagnosed with malignancy, and among them, eight had bone metastasis. Spearman's correlation coefficient between PSA and malignancy was 0.449 (<iP</i ≤ 0.001). Multivariate analysis suggested that the factors (adjusted odds ratio; 95% confidence interval; <iP</i value) such as increasing age (1.127; 1.013, 1.253; 0.027), nodular prostate (22.668; 4.655, 110.377; <iP</i < 0.001), and PSA (1.034; 1.004, 1.064; 0.024) were significant predictors of prostate cancer. All patients with benign prostatic hyperplasia were advised a combination therapy with 5-alpha reductase inhibitor and selective alpha-1 receptor antagonist while those with malignancy were prescribed androgen deprivation therapy with antiosteoporosis therapy. In elderly patients with raised PSA levels or suspicious DRE findings, TRUS-guided prostate is recommended to rule out malignancy and plan appropriate management.

Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng./ml. Prostate specific antigen.

We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization. Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy. Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to data detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6. By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these mean as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.

Evaluation and management of the man who has failed primary curative therapy for prostate cancer.

The recurrence of prostate cancer after potentially curative local therapy is becoming a significant urologic problem. There are few prospective randomized trials, and the optimal diagnostic and treatment strategies for men who fail potentially curative therapy are not known. The experience to date seems to suggest the following as a reasonable approach. A detectable serum PSA level (> or = 0.4 ng/mL) after radical prostatectomy is evidence of residual or recurrent prostate cancer. Men with low- or moderate-grade cancers (Gleason score < 7), with capsular penetration, or with positive surgical margins in whom disease recurs more than 2 years after radical prostatectomy with a PSA doubling time greater than 12 months seem likely to harbor a local recurrence and are the only good candidates for salvage therapy. Unless there is a palpable recurrence, transrectal ultrasound and biopsy are generally not recommended, and CT scanning and bone scintigraphy usually do not provide helpful information. The role of monoclonal antibody scanning is currently investigational. Men with high-grade tumors (Gleason score > or = 7) or with seminal vesicle or lymph node involvement in whom disease recurs within 2 years of radical prostatectomy are most appropriately observed or treated with early hormonal therapy. Men who do not achieve a PSA nadir of 0.5 ng/mL or less within 2 years of radiotherapy are very likely to harbor residual disease. For young healthy men who are willing to accept a substantial risk of impotency, urinary incontinence, and bladder neck contractures, salvage radical prostatectomy is a reasonable option if the preradiation tumor characteristics are acceptable (PSA < 10 ng/mL, Gleason score < or = 6) and if the current PSA is less than 10 ng/mL. Salvage cryotherapy may result in substantial morbidity and should only be offered on an investigational basis. Other men failing radiation may be observed or treated with hormonal therapy. There is seldom a role for repeat biopsy. Because the optimal time to begin hormone therapy is still not known, early or delayed treatment are both reasonable options. Testicular androgen ablation by orchiectomy or LHRH agonists is considered standard therapy. Combined therapy with an antiandrogen does not seem to be beneficial for all patients and should not be routinely used. Sexually active men in whom preservation of potency is important can be offered an investigational regimen such as a 5-alpha-reductase inhibitor combined with an oral antiandrogen or intermittent LHRH agonist therapy. It is hoped that the results of ongoing randomized trials and future research will establish efficient and effective practice guidelines to evaluate and treat men who have failed potentially curative therapy for localized prostate cancer. This remains a very important and controversial topic that will challenge many practicing urologists.

Prostate cancer. Finding and managing it.

Despite development of new technology for the diagnosis and treatment of prostate cancer, the age-adjusted mortality rate for the disease has not declined for nearly half a century. Physicians now have the ability to diagnose very small tumors in asymptomatic patients, but it remains to be determined which subset of patients would benefit most from early identification and treatment. Studies that are currently under way hopefully will clarify what screening protocols, if any, actually reduce the mortality and morbidity that are associated with prostate cancer and its treatment. Until such evidence becomes available, screening measures for the general population are unwarranted, with the possible exception of digital rectal examination performed as part of other healthcare services. Prostate-specific antigen (PSA) determination may have a place in screening patients whose family history puts them at increased risk. In patients with symptoms or findings suggestive of prostate cancer, diagnosis and staging can be accomplished more accurately and easily than ever before with a combination of PSA determination, transrectal ultrasound, ultrasound-guided tissue sampling using a biopsy gun, and the judicious use of imaging techniques such as bone scans, magnetic resonance imaging, and computed tomography. New treatment methods are being studied, and the options available, especially for management of disease progression, are expected to increase. Monitoring of treated patients has been greatly facilitated by determination of PSA levels, which are predictive of both long- and short-term prognosis. Although much work remains to be done, we may finally be on the verge of making real progress in control of prostate cancer.

Prostate-specific antigen

PSA levels can be also increased by prostatitis, irritation, benign prostatic hyperplasia (BPH), and recent ejaculation, producing a false positive result. Digital rectal examination (DRE) has been shown in several studies to produce an increase in PSA. However, the effect is clinically insignificant, since DRE causes the most substantial increases in patients with PSA levels already elevated over 4.0ng/mL. The "normal" reference ranges for prostate-specific antigen increase with age, as do the usual ranges in cancer, as per table below. PSA velocity Despite earlier findings, recent research suggests that the rate of increase of PSA (e.g. >0.35ng/mL/yr, the 'PSA velocity') is not a more specific marker for prostate cancer than the serum level of PSA.

The value of screening tests in the detection of prostate cancer. Part II: Retrospective analysis of free/total prostate-specific analysis ratio, age-specific reference ranges, and PSA density.

The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment. In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308 biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were used to study their capability to increase the specificity of total serum PSA in predicting prostate biopsy results. Using age-specific PSA reference ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies would have been obtained with a loss of detected cancers of 12% (11). For the use of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively. Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less and an abnormal DRE as indicators for biopsy would reduce the number of biopsies by 37% (112) and the number of detected cancers by 11% (7). The biopsy to prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal loss of cancer detection of 3% (2) with a reduction in the number of biopsies of 17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS and DRE would have reduced the number of biopsies by 30% (102), and the number of cancers detected by 6% (4). The most cost-effective protocol for screening prostate carcinoma appears to be prescreening by total serum PSA. The F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL, but the best threshold remains to be assessed.

Prostatic specific antigen and bone scan in the diagnosis and follow-up  of prostate cancer. Can diagnostic significance of PSA be increased?

Prostate cancer (PC) is currently the most frequently diagnosed cancer in males and  constitutes a major health issue in developed countries. On the other hand, the majority  of PC cases are considered clinically not significant and certainly not lethal.  These discrepancies highlight the need for the early detection of especially those cases that have  aggressive features and call for early and radical intervention. The clinical use of prostatic specific antigen (PSA)  towards this end is recognized as inadequate since PSA is prostate specific, but not a PC specific marker, as it is known  to increase in other prostate diseases such as benign hyperplasia, inflammations, transrectal ultrasound examination,  biopsy and after transurethral prostatectomy. However due to lack of other more specific markers, digital rectal  examination combined with serum PSA are suggested for PC screening and diagnosis. With regard to advanced  disease where bone involvement is the rule, nuclear medicine bone scan using radioactive bisphosphonates such  as technetium-99m methylene-diphosphonate is quite common and reliable technique for  detecting and monitoring bone metastases. The major advantage of nuclear scintigraphy is its ability to  reveal bone metastases significantly earlier than the conventional X-ray imaging techniques. PSA density, velocity, doubling  time and free to total PSA ratio increase the significance of serum PSA in diagnosing PC.  The combination of an increased PSA (>20ng/mL) and a high biopsy Gleason score (>8) enhances  the possibility of bone metastases (P<0001) and mandates a bone scan. In conclusion, serum PSA testing is currently  recommended in symptomatic PC patients for disease staging and treatment monitoring and in asymptomatic selected  population groups aged more than 50 years. It is reasonable to suggest that PSA density, velocity, doubling time and free  to total PSA ratio or combining PSA with Gleason score shall greatly increase PSA specificity in detecting  PC cases. Radioisotopic bone scan by SPET or PET can demonstrate  osseous metastases at later stages of PC, but should also be applied in cases falsely considered as an early stage of PC,  for better staging and for periodic follow-up of the disease.

Active surveillance of prostate cancer

Risks of over treatment of prostate cancer Over diagnosis is the detection of a cancer that would otherwise not have been diagnosed in the lifetime of the host if the detection test (e.g., PSA and/or prostate biopsy) had not been performed. Treatment of men who would otherwise not have known about their cancer in the absence of PSA testing and biopsy are over treated. Over treatment exacts a cost to the health care system and potential harm to a patient (decrease in quality of life), with no benefit. Over treatment is most likely to occur when a low grade prostate cancer is detected, especially in an older man. Data from various sources suggest that in the PSA range where many men are undergoing prostate biopsy today (PSA 2-4 ng/ml), 15-25% will have prostate cancer detected, and 80-90% will be low grade.

Prostate-specific antigen

PSA was first measured quantitatively in the blood by Papsidero in 1980, and Stamey carried out the initial work on the clinical use of PSA as a marker of prostate cancer. Serum levels PSA is normally present in the blood at very low levels. The reference range of less than 4ng/mL for the first commercial PSA test, the Hybritech Tandem-R PSA test released in February 1986, was based on a study that found 99% of 472 apparently healthy men had a total PSA level below 4ng/mL. Increased levels of PSA may suggest the presence of prostate cancer. However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a false negative. Obesity has been reported to reduce serum PSA levels. Delayed early detection may partially explain worse outcomes in obese men with early prostate cancer. After treatment, higher BMI also correlates to higher risk of recurrence.

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL.

To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.

Prostate

A digital rectal examination and the measurement of a prostate-specific antigen (PSA) level are usually the first investigations done to check for prostate cancer. PSA values are difficult to interpret, because a high value might be present in a person without cancer, and a low value can be present in someone with cancer. The next form of testing is often the taking of a biopsy to assess for tumour activity and invasiveness. Because of the significant risk of overdiagnosis with widespread screening in the general population, prostate cancer screening is controversial. If a tumour is confirmed, medical imaging such as an MRI or bone scan may be done to check for the presence of tumour in other parts of the body.

Prostate-specific antigen

PSA levels between 4 and 10ng/mL (nanograms per milliliter) are considered to be suspicious and consideration should be given to confirming the abnormal PSA with a repeat test. If indicated, prostate biopsy is performed to obtain a tissue sample for histopathological analysis. While PSA testing may help 1 in 1,000 avoid death due to prostate cancer, 4 to 5 in 1,000 would die from prostate cancer after 10 years even with screening. This means that PSA screening may reduce mortality from prostate cancer by up to 25%. Expected harms include anxiety for 100 – 120 receiving false positives, biopsy pain, and other complications from biopsy for false positive tests.

Prostate-specific antigen

Free PSA Most PSA in the blood is bound to serum proteins. A small amount is not protein-bound and is called 'free PSA'. In men with prostate cancer, the ratio of free (unbound) PSA to total PSA is decreased. The risk of cancer increases if the free to total ratio is less than 25%. (See graph at right.) The lower the ratio is, the greater the probability of prostate cancer. Measuring the ratio of free to total PSA appears to be particularly promising for eliminating unnecessary biopsies in men with PSA levels between 4 and 10ng/mL. However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours. Inactive PSA

Active surveillance of prostate cancer

Most urologists will monitor a patient on surveillance with PSA and digital rectal examination at least biannually, and perform surveillance prostate biopsies at 1-2 year intervals. However, defining disease progression is problematic. Progression in active surveillance programs has been defined based on PSA kinetics or exceeding a given PSA threshold, increased extent of cancer or higher grade disease on prostate biopsy, change in digital rectal examination, and proceeding to curative intervention. Yet, PSA changes and exceeding a given threshold PSA value may not reflect progression of disease. A change in stage or digital rectal examination findings is unusual among patients with low risk disease. Switching from surveillance to curative intervention may be triggered by a patient's personal preference or anxiety and not necessarily by a change in the cancer. Cancer grade is the strongest feature associated with long term freedom from disease in untreated men, and therefore the

Prostate-specific antigen

However, the PSA rate of rise may have value in prostate cancer prognosis. Men with prostate cancer whose PSA level increased by more than 2.0ng per milliliter during the year before the diagnosis of prostate cancer have a higher risk of death from prostate cancer despite undergoing radical prostatectomy. PSA velocity (PSAV) was found in a 2008 study to be more useful than the PSA doubling time (PSA DT) to help identify those men with life-threatening disease before start of treatment. Men who are known to be at risk for prostate cancer, and who decide to plot their PSA values as a function of time (i.e., years), may choose to use a semi-log plot. An exponential growth in PSA values appears as a straight line on a semi-log plot, so that a new PSA value significantly above the straight line signals a switch to a new and significantly higher growth rate, i.e., a higher PSA velocity. Free PSA

Benign prostatic hyperplasia

PSA density, free PSA, rectal examination, and transrectal ultrasonography may be helpful in determining whether a PSA increase is due to BPH or prostate cancer. Ultrasound examination of the testes, prostate, and kidneys is often performed, again to rule out cancer and hydronephrosis.

Prostate cancer screening

One commentator observed in 2011: “[I]t is prudent only to use a single PSA determination as a baseline, with biopsy and cancer treatment reserved for those with significant PSA changes over time, or for those with clinical manifestations mandating immediate therapy..... absolute levels of PSA are rarely meaningful; it is the relative change in PSA levels over time that provides insight, but not definitive proof of a cancerous condition necessitating therapy.“ History Screening of PSA began in the 1990s. In the European Randomized Study of Screening for Prostate Cancer (ERSPC) initiated in the early 1990s, the researchers concluded that PSA-based screening did reduce the rate of death from prostate cancer but created a high risk of overdiagnosis, i.e., 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent just one death from prostate cancer within 9 years.

Prostate biopsy

Prostate biopsy is a procedure in which small hollow needle-core samples are removed from a man's prostate gland to be examined for the presence of prostate cancer. It is typically performed when the result from a PSA blood test is high. It may also be considered advisable after a digital rectal exam (DRE) finds possible abnormality. PSA screening is controversial as PSA may become elevated due to non-cancerous conditions such as benign prostatic hyperplasia (BPH), by infection, or by manipulation of the prostate during surgery or catheterization. Additionally many prostate cancers detected by screening develop so slowly that they would not cause problems during a man's lifetime, making the complications due to treatment unnecessary. The most frequent side effect of the procedure is blood in the urine (31%). Other side effects may include infection (0.9%) and death (0.2%).

Effect of antibiotic treatment on serum PSA and percent free PSA levels in patients with biochemical criteria for prostate biopsy and previous lower urinary tract infections.

Controversy exists as to the influence of inflammatory foci on total and free prostate-specific antigen (PSA) concentrations. The objective was to analyze the biological variations of PSA and percent free PSA (%f-PSA) in patients with biochemical criteria for prostate biopsy (PSA higher than 4 ng/mL and normal rectal examination) and compare them with the variation induced by antibiotic treatment in a cohort of patients with a history of lower urinary tract infections and no clinical evidence of prostatitis. Ninety patients with a history of lower urinary tract infections, non-suspicious digital rectal examination and PSA between 4 and 20 ng/mL were analyzed. PSA concentration and %f-PSA were determined. Forty-five patients were treated with three weeks of ofloxacin, following which marker determination was repeated. All patients underwent ultrasound-controlled transrectal six-core prostate biopsy. Sixty-seven patients presented benign prostatic hyperplasia (BPH) (30 with prostatitic foci) and 23 cancer. Significant variations in PSA (6.97 ng/mL vs. 5.82 ng/mL, p=0.001) and %f-PSA (14.84% vs. 17.53%, p=0.01) were found only in the treated patients. These differences were significant for patients with BPH-associated prostatitic foci and not for patients with BPH or cancer. The tendency was for PSA to decrease (15 treated patients with PSA <4 ng/mL vs. six non-treated patients) and for %f-PSA to increase. The median variation of %f-PSA was greater than that of PSA. When the cutoff for %f-PSA was set at 25%, 18.9% of unnecessary biopsies after the first determination and 20% after the second could be avoided. By associating the reduction in PSA, up to 46% could be avoided in treated patients. Biochemical criteria for prostate biopsy may be modified in patients with a history of lower urinary tract infections due to variations greater than those explained by intraindividual biological variations, and may be influenced by the antibiotic treatment. These results suggest that subclinical inflammatory foci may influence PSA and %f-PSA.

Benign prostatic hyperplasia

Urinalysis is typically performed when LUTS are present and BPH is suspected to evaluate for signs of a urinary tract infection, glucose in the urine (suggestive of diabetes), or protein in the urine (suggestive of kidney disease). Bloodwork including kidney function tests and prostate specific antigen (PSA) are often ordered to evaluate for kidney damage and prostate cancer, respectively. However, checking blood PSA levels for prostate cancer screening is controversial and not necessarily indicated in every evaluation for BPH. Benign prostatic hyperplasia and prostate cancer are both capable of increasing blood PSA levels and PSA elevation is unable to differentiate these two conditions well. If PSA levels are checked and are high, then further investigation is warranted. Measures including PSA density, free PSA, rectal examination, and transrectal ultrasonography may be helpful in determining whether a PSA increase is due to BPH or prostate cancer. Ultrasound examination of the

[Prostatic carcinoma. Screening--when and what?].

Prostate cancer is now the most common cancer and the second most common cause of death from cancer among men. Therapy of curative intention is only possible in organ confined disease. The use of prostate specific antigen (PSA) and digital rectal examination (DRE) results in a three fold increase in prostatic carcinoma detection. Levels of PSA > 4 ng/ml are indications for sextant biopsies of the prostate. There did not exist an intermediate range or 'grey zone' of PSA 4-10 ng/ml where wait and see diagnostic procedure is indicated. In PSA levels > 10 ng/ml curative therapy can only performed in 15-44% of the cases. PSA and DRE examination should be performed between the age of 50 and 70 years when life expectancy exceeds ten years. In case of familiar history the case finding has to start at the age of 45. There is no support for the common opinion that early detection finds clinically insignificant cancer since autoptical prevalence of prostate cancer is about 40% and early detection discover only 3-4%. Results about the usefulness of active screening in a population will be available in 2005.

Are prostatic biopsies necessary in men aged > or =80 years?

To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.

Prostate cancer screening

Other A number of biomarkers for prostate cancer exist. These include: The 4Kscore combines total, free and intact PSA together with human kallikrein 2. It is used to try to determine the risk of a Gleason score greater than 6. The Prostate Health Index (PHI) is a PSA-based blood test for early prostate cancer screening. It may be used to determine when a biopsy is needed. Prostate cancer antigen 3 (PCA3) is a urine test that detects the overexpression of the PCA3 gene, an indicator of prostate cancer. ConfirmMDx is performed on tissue taken during a prostate biopsy. The test identifies men with clinically significant prostate cancer who would benefit from further testing and treatment. It can also help men without significant prostate cancer avoid unnecessary repeat biopsies.

[Prostate cancer screening using prostate-specific antigen (PSA) determinations in plasma. National Academy of Medicine].

Prostate cancer is the most frequent cancer in man above 50 years. There is an increase in its incidence due to the longer life of the population. Prostate cancer is a slowly progressing disease. If life expectation is smaller than 10 years, the risk of death from another cause is greater than that from cancer whereas it is the opposite in younger patients. Therefore, screening of the disease by rectal examination and prostatic specific antigen (PSA) assay is necessary, confirmation being obtained by prostate biopsy. Total prostatectomy and radiotherapy can cure the disease or inhibit its progression. Plasma PSA is a general marker of prostate lesions. It is easy to measure and the cost of the assay is acceptable; but its specificity and its sensitivity remain too low. In order to improve these two parameters, it has been proposed to follow PSA kinetics and to measure the ratio free PSA/total PSA. Taken together, these data lead us to recommend, in agreement with the French Association of Urology, that a PSA assay be proposed and a rectal examination be performed every year by a general practitioner in men between 50 and 75 years and from 45 years in case of familial history. If an anomaly is found, the patient must take advice from an urologist who will decide which examinations and which treatment are to be proposed. Moreover, studies are necessary to compare the principal treatments in the long term, to precise the distribution with age of plasma PSA in the population and to improve the specificity and the sensitivity of the screening test.

Prostate cancer screening

Screening precedes a diagnosis and subsequent treatment. The digital rectal examination (DRE) is one screening tool, during which the prostate is manually assessed through the wall of the rectum. The second screening tool is the measurement of prostate-specific antigen (PSA) in the blood. The evidence remains insufficient to determine whether screening with PSA or DRE reduces mortality from prostate cancer. A 2013 Cochrane review concluded PSA screening results in "no statistically significant difference in prostate cancer-specific mortality...". The American studies were determined to have a high bias. European studies included in this review were of low bias and one reported "a significant reduction in prostate cancer-specific mortality." PSA screening with DRE was not assessed in this review. DRE was not assessed separately.

[Clinical course of patients with negative initial prostate biopsy].

Of 227 men with a negative initial biopsy, the clinical course of 99 men who could be regularly followed using prostate specific antigen (PSA) determination was retrospectively analyzed. A repeat biopsy was recommended if the men showed persistent elevation of PSA > 10 ng/ml, PSA velocity (PSAV) > 0.75 ng/ml/year, or persistent abnormality on digital rectal examination and/or transrectal ultrasonography. A repeat biopsy was performed on 43 men. Because of the indication for a repeat biopsy, the PSAV of the 43 men who received a repeat biopsy was higher than that of the 56 men who did not. Clinically organ-confined cancer was detected in 18 patients (detection rate 41.9%). The patients having cancer had a higher PSAV (median 1.950) than those without the disease (median 0.900). Of 19 men aged 75 years and older at the initial biopsy, a repeat biopsy revealed organ-confined cancers in 4 out of 10 men. During follow-up of the 19 elderly men, 11 developed co-morbid illnesses such as cerebral infarction, ischemic heart diseases and other malignancies, and 4 died of the diseases. Thus, PSAV seems to be the best parameter for a repeat biopsy. Elderly men may not benefit from a repeat biopsy because they are unlikely to have lethal prostate cancer and highly likely to develop co-morbid illness that would affect their life-span.

The role of empiric antibiotic treatment in preventing unnecessary prostate biopsies in asymptomatic patients with PSA levels between 4 and 10 ng/ml.

To evaluate exclusion of prostate cancer (PCa) by using empiric antibiotic treatment for patients with total prostate specific antigen (PSA) between 4-10 ng/ml. A hundred asymptomatic men with a PSA between 4-10 ng/ml and normal digital rectal examination (DRE) were enrolled in this randomized prospective study. The treatment group (n=50) was given 400 mg of ofloxacin daily for 4 weeks, whereas the control group (n=50) was followed without any treatment. At the end of the four weeks, repeat PSA were measured and all patients underwent transrectal ultrasound (TRUS) guided biopsy, regardless of the repeat PSA levels. Totally 22 patients (22%) had prostate cancer (9 in treatment group and 13 in control group). A significant PSA decrease was observed in the treatment group at repeat PSA measurements (p=0.001). The PSA drop was also significantly more in patients without PCa than with PCa (p=0.028). In patients whose repeat PSA after antibiotic treatment decreased below 4 ng/ml, 2 times as many patients (16.6%) had PCa in the control group when compared with the treatment group (8.3%). On the other hand, in patients whose repeat PSA remained above 4 ng/ml, PCa was detected in 27.3% of the patients in the control group and 21% in the treatment group. Empirical antibiotic treatment in asymptomatic patients with a PSA level 4-10 ng/ml and a normal DRE may be used to select prostate biopsy candidates. Studies with higher number of patients may result in more powerful associations with narrower confidence intervals for increased confidence.

Prostate cancer screening

Screening with PSA has been associated with a number of harms including over-diagnosis, increased prostate biopsy with associated harms, increased anxiety, and unneeded treatment. The evidence surrounding prostate cancer screening indicates that it may cause little to no difference in mortality. On the other hand, up to 25% of men diagnosed in their 70s or even 80s die of prostate cancer, if they have high-grade (i.e., aggressive) prostate cancer. Conversely, some argue against PSA testing for men who are too young, because too many men would have to be screened to find one cancer, and too many men would have treatment for cancer that would not progress. Low-risk prostate cancer does not always require immediate treatment, but may be amenable to active surveillance. A PSA test cannot 'prove' the existence of prostate cancer by itself; varying levels of the antigen can be due to other causes.

Early detection of prostate cancer. Part II: Estimating the risks, benefits, and costs. American College of Physicians.

To evaluate the potential benefits, harms, and economic consequences of digital rectal examination and measurement of prostate-specific antigen (PSA) for the early detection of prostate cancer. Relevant studies were identified from a MEDLINE search (1966 to 1995), reviews, bibliographies of retrieved articles, author files, and abstracts. Probabilities for individual clinical outcomes were derived from various sources, including the largest screening study of community volunteers to data, analyses of Medicare claims, and recently published meta-analyses of the outcomes of alternative treatment strategies. Cost estimates were based on the 1992 Medicare fee schedule. A cost-effectiveness model for one-time digital rectal examination and PSA measurement was constructed to examine the possible outcomes. If a favorable set of assumptions is used, one-time digital rectal examination and PSA measurement may increase average life expectancy by approximately 2 weeks at a reasonable marginal cost for men who are between 50 and 69 years of age. Considerable iatrogenic illness would occur. If less favorable assumptions are used, the estimated net benefit would decrease and cost-effectiveness ratios would dramatically increase. Even if favorable assumptions are used, the model suggests that screening adds only a few days to the average life expectancy of men who are older than 69 years of age. If the assumptions are less favorable, older men are harmed. The model suggests that screening may be reasonable in younger men if optimistic assumptions consistent with existing observational data are made. The lack of direct evidence showing a net benefit of screening for prostate cancer seems to mandate more clinician-patient discussion for this procedure than for many other routine tests.

High-grade prostatic intraepithelial neoplasia

Diagnosis HGPIN is diagnosed from tissue by a pathologist, which may come from: a needle biopsy taken via the rectum and, surgical removal of prostate tissue: transurethral resection of the prostate - removal of extra prostate tissue to improve urination (a treatment for benign prostatic hyperplasia), radical prostatectomy - complete removal of prostate and seminal vesicles (a treatment for prostate cancer). Blood tests for prostate specific antigen (PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum, fine needle aspiration or medical imaging studies (such as magnetic resonance imaging) are not useful for diagnosing HGPIN. Treatment HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.

[Screening for early detection of prostate cancer (first experience in Israel)].

Prostatic cancer (PC) is second only to lung cancer as a cause of cancer mortality in men word-wide. In Israel it is the most common cause of cancer mortality in men, after lung cancer and colo-rectal cancer. We screened, for the first time in Israel, for prostatic cancer using serum levels of PSA and a digital rectal examination (DRE). The purpose was not only to diagnose PC but also to increase public awareness of the condition. 300 men in the Haifa area who met statistical criteria for early diagnosis of PC participated. They filled a questionnaire regarding risk factors for PC (age, family history (FH) of prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA sampling) and were examined. Those who had out-of-range, age-related PSA values, or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and guided biopsy of the prostate. Those with a positive biopsy for PC underwent radical prostatectomy or radiation therapy. 41 (14.3%) had out-of-range, age-related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason 4-6). Correlation between age and PSA has been proven statistically significant (p < 0.05). Symptoms of urinary tract obstruction and nocturia were related to a high PSA (p = 0.035 and 0.002, respectively). Those with PC had at least 1 symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age-related PSA had a positive predictive value of 17.1%. Results of our annual screening for early detection of PC using age-related PSA, and DRE are encouraging: cases detected were clinically significant and treatable. It would appear that screening for PC will result in decreasing the incidence of metastatic cancer and therefore mortality.

Prostate-specific antigen

Following radiation therapy of any type for prostate cancer, some PSA levels might be detected, even when the treatment ultimately proves to be successful. This makes it more difficult to interpret the relationship between PSA levels and recurrence/persistence of prostate cancer after radiation therapy. PSA levels may continue to decrease for several years after radiation therapy. The lowest level is referred to as the PSA nadir. A subsequent increase in PSA levels by 2.0ng/mL above the nadir is the currently accepted definition of prostate cancer recurrence after radiation therapy.


Difficult question. The patient presents with thrombotic microangiopathy (TMA) with acute renal failure. This points to HUS, TTP, drug-induced TMA, or TMA mediated by complement, coagulation, or metabolism. Normal ADAMTS-13 levels rule out TTP (incorrect choice 1). The absence of gastrointestinal symptoms rules out typical Shiga toxin HUS (incorrect choice 4). Pneumococcal infections can also cause HUS, although it is rare and more so in adults. The history of respiratory infection (not specified, it could be pneumococcal pneumonia) together with the absence of DIC data (no mention of bleeding or altered coagulation tests) makes me think of atypical HUS (option 2 correct).

Difficult question. The patient presents with thrombotic microangiopathy (TMA) with acute renal failure. This points to HUS, TTP, drug-induced TMA, or TMA mediated by complement, coagulation, or metabolism. Normal ADAMTS-13 levels rule out TTP ([HIDDEN]). The absence of gastrointestinal symptoms rules out typical Shiga toxin HUS ([HIDDEN]). Pneumococcal infections can also cause HUS, although it is rare and more so in adults. The history of respiratory infection (not specified, it could be pneumococcal pneumonia) together with the absence of DIC data (no mention of bleeding or altered coagulation tests) makes me think of atypical HUS ([HIDDEN]).

A 19-year-old male with no past history of interest comes to the emergency department because after a respiratory infection he presents with asthenia, malaise, oliguria and headache. Physical examination: BP 210/120 mmHg, fundus with hypertensive retinopathy grade III. Laboratory tests: Hb 7.4 g/dl, platelets 85,000/mm3, 2-3 schistocytes in the peripheral blood smear, LDH 950 IU/ml, serum creatinine 8.75 mg/dl. Urine system: proteinuria 300 mg/dl, sediment 15 red blood cells per field. ADAMTS-13 levels are normal. Given these findings, what would be your main diagnostic suspicion?

Thrombotic Microangiopathy in a Severe Pediatric Case of COVID-19.

In this case report, we report a pediatric patient with COVID-19 and atypical hemolytic uremic syndrome (aHUS). A 3-year-old girl with fever and respiratory distress was admitted to the hospital. The patient tested positive for COVID-19 by a PCR test. As her respiratory distress increased and blood gas indicated deep respiratory acidosis on the third day of the pediatric intensive care unit follow-up, the patient was intubated and ventilated. Thorax computerized tomography (CT) showed bilateral effusion and atelectasis. During her follow-up, the pleural effusion resolved but there were marked consolidation areas and ground glass opacities compatible with COVID-19 on the follow-up CT. On the 10th day, she became anuric and developed progressive thrombocytopenia and persistent microangiopathic hemolytic anemia, which were suggestive of HUS given a high creatinine level (1.9 mg/dl), an undetectable haptoglobin level, reticulocytosis (8%), and an LDH level of 2540 U/l. Direct Coombs test returned negative. Examination of a peripheral blood smear revealed schistocytes. Disseminated intravascular coagulation was ruled out by normal INR and PTT. In the light of the available findings, we considered the patient to have thrombotic microangiopathy (TMA) triggered by COVID-19. It was not a TTP-form of TMA but rather an aHUS type, based on an ADAMTS13 activity level >5%. Hence, plasmapheresis was performed with fresh frozen plasma (FFP). After 4 weeks, she became completely asymptomatic, and her hemodynamic parameters normalized. COVID-19 induced uncontrolled complement activation leading to the development of aHUS. Early diagnosis and treatment may reduce morbidity and mortality since its treatment options.

Thrombotic thrombocytopenic purpura

TTP is characterized by thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to microangiopathic hemolytic anemia and thrombocytopenia. This characteristic is shared by two related syndromes, hemolytic-uremic syndrome (HUS) and atypical hemolytic uremic syndrome (aHUS). Consequently, differential diagnosis of these TMA-causing diseases is essential. In addition to TMA, one or more of the following symptoms may be present in each of these diseases: neurological symptoms (e.g. confusion, cerebral convulsions seizures,); kidney impairment (e.g. elevated creatinine, decreased estimated glomerular filtration rate [eGFR], abnormal urinalysis); and gastrointestinal (GI) symptoms (e.g. diarrhea nausea/vomiting, abdominal pain, gastroenteritis. Unlike HUS and aHUS, TTP is known to be caused by an acquired defect in the ADAMTS13 protein, so a lab test showing ≤5% of normal ADAMTS13 levels is indicative of TTP. ADAMTS13 levels

Malignant hypertension as a rare cause of thrombotic microangiopathy.

Malignant hypertension can occasionally be associated with microangiopathic haemolytic anaemia. A 38-year-old male presented with nausea, vomiting, loss of appetite and oliguria for 2 weeks. He was diagnosed with hypertensive emergency with cardiac and renal dysfunction. Interestingly, further workup was diagnostic for the presence of thrombotic microangiopathy (TMA): haemoglobin =12.7 g/dL, indirect bilirubin =2.0 mg/dL, haptoglobin ≤6 mg/dL, platelet count =121 000/μL and schistocytes on peripheral smear. At the outset, the cause of TMA was unclear. Patient denied having diarrhoea, making haemolytic uremic syndrome less likely. A normal ADAMTS13 activity test ruled out thrombotic thrombocytopaenic purpura. Malignant hypertension induced TMA was highest on the differential and plasma exchange was deferred. Renal biopsy revealed features of TMA and malignant nephrosclerosis. Patient eventually became dialysis dependent. Aggressive blood pressure control was obtained with multiple medications.

[Thrombotic thrombocytopenic pupura (TTP)--remission following treatment with high-dose immunoglobulin].

A 60-year-old man was admitted to our hospital because of fever, hemorrhagic tendency, anemia and neurological abnormality. A blood count revealed that the hemoglobin was 6.8 g/dl, the reticulocyte was 17.3 percent with 2 erythroblasts per 100 white cells, the white cell count was 7,100/microliters and the platelet count was 0.8 x 10(4)/microliters. Peripheral blood smear demonstrated marked fragmentation of red cells. Bone marrow examination disclosed the marked erythroid hyperplasia. Although the bleeding time was prolonged (14 minutes 30 seconds), the other hemostatic data were within normal limits. The serum bilirubin level was 1.57 mg/dl; LDH level, 1,437 U/l; creatinine level, 0.92 mg/dl; BUN level 14.7 mg/dl. Haptoglobin was below 10 mg/dl. Results of immunological tests were all negative except the result of PAIgG (576.6 ng/10(7) cells). The urinalysis showed proteinuria, microhematuria and trace granular and hyaline casts. A diagnosis of thrombotic thrombocytopenic purpura was made. The patient was initially treated with prednisolone (60 mg), aspirin (1,000 mg), dipyridamole (150 mg), gabexate mesilate (1.5 g), sodium oxagrel (80 mg) daily with little response. The thirty days after admission, infusion of gamma globulin (20 g, daily) was given for 3 days. The clinical state and laboratory findings became dramatically improved shortly after the administration of gamma globulin and the laboratory data came to be normalized after 1 month. After ten months of this treatment, the patient is remained asymptomatic and the hematological data are within normal range without using any drug. A trial seems justified to confirm the value of this mode of therapy.

Manifestation of paroxysmal nocturnal hemoglobinuria as repeated acute kidney injury.

The triad of hemolytic anemia, pancytopenia, and thrombosis makes paroxysmal nocturnal hemoglobinuria (PNH) a truly unique clinical syndrome. Intravascular hemolysis in PNH can lead to a severe hemolytic episode with massive hemoglobinuria which can cause acute kidney injury (AKI) probably from acute tubular necrosis (ATN). A 15 -year-old girl was admitted with history of fever, diarrhea, vomiting followed by decreased urine output since 3 days. Urinalysis showed nil protein, no red blood cells (RBCs) on microscopy. Plasma hemoglobin level, total leukocyte count, platelet count, and serum creatinine were 6.5 gm/dl, 6440/μl, 205 000/μl, and 3.1 mg/dl, respectively. She received 3 units of packed red blood cells and the patient was discharged with normal renal function test with a diagnosis of acute gastroenteritis with recovered AKI. After 8 months she again had fever, vomiting, nausea with decreased urine output since 3 days. Laboratory investigations showed hemoglobin - 5.5 gm/dl, total leukocyte count - 1550/ μl, platelet count - 165000/μl, and serum creatinine - 4.89 mg/dl. Serum LDH level was 2188 U/l. She was managed conservatively with steroids, antibiotics and she recovered her kidney functions to normal in a week. Presentation of repeated AKI with hemolytic anemia in a short span after fever led us to perform flow cytometric analysis of peripheral blood granulocytes which revealed the presence of PNH clone. PNH may present with renal disease and anemia only even without classical history of hematuria or venous thrombosis. Thus it needs high index of suspicion as early diagnosis and treatment will help in preventing repeated episodes of AKI and thus chronic kidney disease.

Atypical hemolytic uremic syndrome

Clinical signs and symptoms of complement-mediated TMA can include abdominal pain, confusion, fatigue, edema (swelling), nausea/vomiting and diarrhea. aHUS often presents with malaise and fatigue, as well as microangiopathic anemia. However, severe abdominal pain and bloody diarrhea are unusual. Laboratory tests may also reveal low levels of platelets (cells in the blood that aid in clotting), elevated lactate dehydrogenase (LDH, a chemical released from damaged cells, and which is therefore a marker of cellular damage), decreased haptoglobin (indicative of the breakdown of red blood cells), anemia (low red blood cell count)/schistocytes (damaged red blood cells), elevated creatinine (indicative of kidney dysfunction), and proteinuria (indicative of kidney injury). Patients with aHUS often present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications,

[An elderly case of thrombotic thrombocytopenic purpura].

A 78-year-old woman was admitted to our hospital because of disorientation and fever on January 21, 1992. Two days before admission she experienced vomiting, anorexia and general malaise. Laboratory examinations on admission disclosed a hemoglobin level of 11.1 g/dl and a platelet count of 8,000/microliters. The peripheral blood smear revealed anisocytosis with numerous schistocytes and poikilocytes. Polychromatophilic and nucleated red blood cells were also seen, and the reticulocyte count was 38/1000. Her serum lactate dehydrogenase (LDH) value was 2,977 WU and the total serum bilirubin level was 3.5 mg/dl with 2.7 mg/dl indirect reacting fraction. Serum creatinine was 4.7 mg/dl. Her consciousness became semicomatose after a systemic seizure which lasted approximately 15 seconds and her hemoglobin level decreased to 8.5 g/dl on hospital day 2. Therefore, we diagnosed her as having thrombotic thrombocytopenic purpura (TTP) because of the presence of all 5 features, that is, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic abnormalities, renal dysfunction and fever. A plasmapheresis with fresh frozen plasma (FFP) replacement was begun on that day. She was also treated with anti-platelet agents, 80 mg/day aspirin, and 300 mg/day dipyridamole. Moreover, packed red blood cells (PRC) were infused. While also receiving diphenylhydantoin and phenobarbital to prevent convulsions, status epilepticus developed on day 3. Because of inhibited spontaneous respiration which was an adverse effect derived from diazepam and sodium thiamylal administered intravenously to treat the status epilepticus, an artificial respiration was initiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Atypical Hemolytic Uremic Syndrome With the p.Ile1157Thr C3 Mutation Successfully Treated With Plasma Exchange and Eculizumab: A Case Report.

To describe a case of atypical hemolytic uremic syndrome induced by influenza A infection with the p.Ile1157Thr C3 mutation. Clinical observations of a patient. Case reports. Data extracted from medical records, after patient's consent. Four days prior to presentation to our hospital, a 16-year-old adolescent had a fever and arthralgia with hematuria. He was found to be positive for type A influenza and prescribed oseltamivir and acetaminophen by a primary-care physician. A bleeding tendency and purpura in the extremities and on the trunk developed; therefore, he was transferred to Chiba University Hospital. Hematology revealed severe thrombocytopenia, hyperbilirubinemia, and acute kidney injury. Aspartate aminotransferase, lactate dehydrogenase, and potassium could not be determined because of severe hemolysis. Highly elevated blood urea nitrogen and creatinine levels indicated acute kidney injury. A platelet count of 24,000/μL indicated thrombocytopenia, with low hemoglobin level. Peripheral blood profiling identified schistocytes. Continuous hemodiafiltration and plasma infusion were initiated immediately; however, he became oliguric. Plasma exchange was initiated on ICU day 3, but decreased urine output, hemolysis, and thrombocytopenia persisted. IV eculizumab therapy was initiated on day 7 and resulted in recovery of these symptoms and also successful discontinuation of renal support. The patient showed a stable condition without recurrence of hemolytic findings and acute kidney injury and is currently on maintenance therapy of eculizumab (1,200 mg, every other week) without any relapse of atypical hemolytic uremic syndrome symptoms. A plasma sample collected prior to initiation of plasma exchange showed an disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 activity level of 104.9%. The absence of both Shiga toxin-producing <iEscherichia coli</i in feces led to suspicion of atypical hemolytic uremic syndrome. Subsequent genetic analysis identified a mutation in <iC3</i (p.Ile1157Thr), confirming the diagnosis of atypical hemolytic uremic syndrome. Although managing thrombocytopenia secondary to infection, inclusion of atypical hemolytic uremic syndrome in the differential diagnosis at an early stage is important in clinical practice.

Severe renal failure and thrombotic microangiopathy induced by malignant hypertension successfully treated with spironolactone.

Malignant hypertension can cause thrombotic microangiopathy (TMA) characterized by hemolytic anemia and thrombocytopenia. On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). Distinguishing these entities is important because of therapeutic implications. Plasmapheresis should be initiated as soon as possible if we are dealing with TTP. We describe the case of a 30-year-old man referred to our hospital with malignant hypertension, severe renal failure and TMA: haemoglobin=9g/dL, total bilirubin=0.4mg/dL, haptoglobin≤10mg/dL, platelet count=59,000/μL and schistocytes on peripheral smear. He required initiation of hemodialysis. Additionally, we considered that the possible cause of TMA was malignant hypertension according to the presence of hypertensive retinopathy and thrombocytopenia which remitted only with blood pressure control, hence, plasmapheresis was not given. Renal function did not improve and the patient remained chronic hemodialysis. Intensive therapy for hypertension with a combination of antihypertensive drugs including spironolactone successfully lowered his blood pressure without developing hyperkalemia.

[Diabetes mellitus as a rare complication of hemolytic uremic syndrome--case report].

A 4-year-old girl was hospitalized in a local hospital with bloody diarrhoea, vomitus and abdominal pain. Because of acute abdominal symptoms she underwent appendectomy after which convulsions and acute respiratory distress were noticed. The child was transferred to the intensive care unit. During the examination she was unconscious, pale, oedematous with scattered ecchymoses, severe hypertension and urine output diminished to several ml per day. Routine blood tests showed microangiopathic anaemia, thrombocytopenia (52000/ul.) and uremia. Proteinuria and hematuria were revealed on urine examination. Among coagulation parameters kaolin-kefalin time (69 s) and D-dimers (2000-4000/ul.) were abnormal. On the strength of history, clinical and laboratory investigation the diagnosis of D-positive hemolytic uremic syndrome was established. Controlled artificial respiration (for 10 weeks), total parenteral alimentation (TPN), antihypertensive treatment and diuretics (furosemide, dopamine) were introduced. Daily temporary access hemodialyses were performed for 4 weeks. Subsequently peritoneal dialysis was started for 2 weeks. Despite the appropriate TPN glucose blood levels were unexpectedly high from first days from admission (200-330 mg%). Intensive intravenous insulin therapy was performed for 50 days. The child was discharged after 72 days with moderate renal function impairment (blood urea-53 mg%, creatinine-1,2 mg%), mild hypertension and proteinuria. Additional factor prone to thrombotic events was the 4G/4G genotype responsible for increased PAI-1 blood concentration, which may result in intensified fibrinolysis inhibition. Diabetes mellitus as a rare immunological complication of haemolytic uremic syndrome was suspected on the following evidence: positive anti-GAD antibodies (ELISA), elevated levels of glycosylated haemoglobin A1c, three-fold reduction of blood C-peptide concentration, negative family history for diabetes. After 12 y of follow up glucose and C-peptide concentrations were normal. Glucose loading test gave adequate response. Kidney function was decreased with serum creatinine 1.7-1.9 mg/dl and urea 60-75 mg/dl.

[Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure, mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case].

Disseminated intravascular coagulopathy (DIC) is characterized as activation of the clotting system resulting in fibrin thrombi, gradually diminishing levels of clotting factors with increased risk of bleeding. Basically two types of DIC are distinguished: (1) chronic (compensated) - with alteration of laboratory values and (2) acute (non-compensated) - with severe clinical manifestations: bleeding, shock, acute renal failure (ARF), transient focal neurologic deficit, delirium or coma. Chronic DIC related to metastatic neoplasia is caused by pancreatic, gastric or prostatic carcinoma in most of the cases. Incidence rate of DIC is 13-30% in prostate cancer, among those only 0.4-1.65% of patients had clinical signs and symptoms of DIC. In other words, chronic DIC is developed in one of eight patients with prostate cancer. DIC is considered as a poor prognostic factor in prostatic carcinoma. The similar clinical and laboratory findings of TTP-HUS (thrombotic thrombocytopenic purpura - hemolytic uremic syndrome) and DIC makes it difficult to differentiate between them. A 71 years old male patient with known chronic obstructive pulmonary disease, benign prostatic hyperplasia, significant carotid artery stenosis, gastric ulcer and alcoholic liver disease was admitted to another hospital with melena. Gastroscopy revealed intact gastric mucosa and actually non-bleeding duodenal ulcer covered by clots. Laboratory results showed hyperkalemia, elevated kidney function tests, indirect hyperbilirubinemia, increased liver function tests, leukocytosis, anemia, thrombocytopenia and elevated international normalized ratio (INR). He was treated with saline infusions, four units of red blood cells and one unit of fresh frozen plasma transfusions. Four days later he was transported to our Institution with ARF. Physical examination revealed dyspnoe, petechiae, hemoptoe, oliguria, chest-wall pain and aggressive behavior. Thrombocytopenia, signs of MAHA (fragmentocytes and helmet cells in the peripheral blood), normal INR, elevated lactate dehydrogenase (LDH) and ARF suggested TTP-HUS. Hemodialysis and six plasmaferesis (PF) were carried out. After the fifth PF, skin manifestations of thrombotic microangiopathy occurred on the feet. Clotting analysis revealed elevated D-dimer (>5 μg/mL), normal fibrinogen (3.2 g/L), a slightly raised INR (1.36) and activated partial prothrombin time (APTT) (45.8 sec), normal reticulocyte (57 G/L) and a slightly low platelet count (123 G/L), which proved to be chronic DIC. Therapeutic dose of low-molecular-weight heparin (LMWH) was started. Elevated prostate-specific antigen (PSA) (109.6 ng/mL) suggested prostatic carcinoma. Prostate biopsy revealed adenocarcinoma (Gleason: 4+4 for left lobe and 3+3 for right lobe). Elevated alkaline phosphatase suggested metastases in the bone, which were confirmed by bone scintigraphy. Combined androgen blockade (CAB) was started. After three months follow-up our patient's status is satisfactory. PSA is in the normal range (4.6 ng/mL). Thrombocytopenia of uncertain origin with normal or raised INR, APTT, elevated D-dimer, normal fibrinogen and reticulocyte count prove the diagnosis of chronic DIC. This process warrants searching for metastatic neoplasia. Due to the relatively low serum levels of circulating procoagulant factors (e.g. tissue factor), therapeutic dose of LMWH can be used with good efficiency in chronic DIC with low risk of bleeding. Severe DIC as a complication of metastatic prostate cancer can be treated by androgen deprivation therapy (ADT) or CAB in combination with ketokonazole and concomitant use of supportive treatment. Deme D, Ragán M, Kovács L, Kalmár K, Varga E, Varga T, Rakonczai E. Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case.

Hemolytic Uremic Syndrome Associated with Norovirus Gastroenteritis: Case Report and Literature Review.

A previously healthy 3-year-old girl was admitted with fever, nonbloody diarrhea, vomiting for 3 days, and oliguria. Physical examination showed fatigue, pale appearance, hypertension, and mild periorbital edema. Laboratory examinations revealed anemia, thrombocytopenia, acute kidney injury, high LDH, and low haptoglobin levels. Urinalysis showed proteinuria and hematuria. Schistocytes and helmet cells were detected in the peripheral blood smear. There were no electrolyte imbalance and hypocomplementemia. Direct Coombs and viral panel were negative. Blood, urine, throat, and stool cultures were negative. Norovirus GII was positive in stool PCR, while other diarrheal agents were negative. The patient was diagnosed with norovirus gastroenteritis-induced hemolytic uremic syndrome (HUS). Furosemide was started for oliguria and hypertension, and blood pressure was controlled with oral nifedipine. On the 12th day of hospitalization, he was discharged with fully recover. To date, norovirus-associated HUS has been reported in 5 cases. Two of these are adult cases and the other three and our case are pediatric patients. In this case report and literature review, we observed that norovirus can cause HUS, especially in children, with a milder course than other types of HUS. The reason why it is more complicated in adult cases may be the presence of an additional underlying kidney disease. Since it was detected coincidentally in 1 case in the literature, it may be useful to screen for mutations in the complement pathway that may cause aHUS, if possible, in diarrhea-associated HUS caused by norovirus agents, but it was not present in our case.

A Case of Recurrent Thrombotic Microangiopathy Caused by Hypertensive Urgency.

A 26-year-old man presented to the emergency room with abdominal pain, nausea, and vomiting for four days. His medical history was significant for hypertension and end-stage renal disease managed with hemodialysis. He had been noncompliant with the antihypertensive regimen which included nifedipine, hydralazine, and spironolactone. At presentation, his blood pressure was 231/123 mmHg. Laboratory workup showed white blood count 17.3 × 109/L (normal range: 4.5 to 11.0 × 109/L), hemoglobin 7.8 gm/dL (normal range: 13.5 to 17.5 g/dL), platelet count 46 × 109/L (normal range: 150 to 400 × 109/L), reticulocyte count 7.8%, total bilirubin 1 mg/dL (normal range: 0.1 to 1.2 mg/dL), lactate dehydrogenase 1,235 U/L (normal range: 140 to 280 U/L), haptoglobin < 10 mg/dL, and a direct Coomb's test was negative. Numerous schistocytes were identified on the peripheral blood smear. The patient was diagnosed with thrombotic microangiopathy secondary to severe hypertension and was started on intravenous nicardipine. With appropriate blood pressure control, hematological parameters improved with normalization of the platelet count within 10 days. Notably, the patient had one similar episode of hypertension-induced thrombotic microangiopathy within a period of the last three months and ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13) activity was normal on his previous admission.

Eculizumab experience in an adult patient with atypical hemolytic uremic syndrome.

Atypical hemolytic-uremic syndrome is a disease characterized by nonimmune hemolytic anemia, thrombocytopenia, and renal failure. In this study, we present a case of a patient with atypical hemolytic-uremic syndrome treated successfully with eculizumab. A 20-year-old female was admitted with clinical signs of atypical hemolytic syndrome. The laboratory findings were as follows: hemoglobin 9.2 g/dL, platelet count 18 × 103/μL, creatinine 4.69 mg/dL, schistocytes were in peripheral blood smear, lactate dehydrogenase 2080 U/L, and emergency plasmapheresis procedure with fresh frozen plasma were initiated. The patient was anuric within 12 h of her admittance. ADAMTS13 activity was normal. Her mother's cousin developed acute rejection immediately after receiving a renal transplant and died two months later. As she did not respond to the treatment and considering her family history, eculizumab was initiated which resulted in platelet counts starting to rise on day 5, and the patient no longer needed dialysis after 22 days.

[A case of hemolytic uremic syndrome associated with circulating anticoagulant].

A previously well 66-year-old woman was admitted to our hospital because of severe abdominal pain, oliguria, jaundice and hemoglobinuria. At admission, the following values were obtained: red blood cell count 261 x 10(4)/mm3, serum creatinine 2.8mg/100ml, total bilirubin 8.0mg/ml, indirect bilirubin 5.7mg/100ml, LDH 13886 WU, negative direct and indirect Coomb's test and peripheral blood smear showing schistocytosis. She was diagnosed as hemolytic uremic syndrome and was successfully treated with plasma infusion, plasma exchange and hemodialysis. The results of the tests for verotoxin titer of E. coli O157: H7 and circulating anticoagulant were positive. The test result for anticoagulant eventually became negative during her clinical course. In this case, circulating anticoagulant might have contributed to the pathogenesis of hemolytic uremic syndrome.

Diagnostic dilemma in postpartum associated hemolytic uremic syndrome in a 38th week pregnant 31-year-old Congolese: a case report.

Thrombotic microangiopathy is associated with HELLP syndrome, thrombotic thrombocytopenic purpura, or atypical hemolytic uremic syndrome (aHUS) during pregnancy. Standard laboratory and physical examinations can help distinguish between these three diseases promptly and guide their management. This is critical because their managements and prognoses differ considerably. The ADAMTS13 test, complement tests, and biopsies can help ascertain the diagnosis; however, they take time, and are not widely available. In this case report, we present a case that highlights the diagnostic and therapeutic dilemmas associated with the aforementioned diseases. A 31-year old P3G3 patient presented at 38 weeks with high blood pressure, bilateral pitting edema, and a low fetal heart rate. A cesarean section was performed to extract the fetus. On postoperative day 2, the suites were marked by anemia, low platelet count, acute kidney injury, declining liver function, and the presence of schistocytes on the peripheral thin smear. The patient was lucid, coherent, and presented no neurological deficits. The ADAMTS13 test and anti-complement therapy were not readily available, so the team made a presumptive diagnosis of aHUS based on the history, clinical presentation, and standard laboratory results. Due to a lack of anticomplement therapy, the patient was prescribed four sessions of hemodialysis. The renal function and platelet count gradually increased, and the patient was discharged on postoperative day 18. The patient was followed for over a year and did not present relapses of thrombocytopenia or microangiopathic hemolytic anemia. The prompt diagnosis and management of aHUS lead to favorable outcomes. Healthcare providers should be able to rapidly differentiate between pregnancy-associated thrombotic microangiopathies and prescribe appropriate management. Here, we highlighted the challenges of diagnosing and managing postpartum associated aHUS in a low-resource setting.

Upshaw–Schulman syndrome

Diagnosis A diagnosis of TTP is based on the clinical symptoms with the concomitant presence of thrombocytopenia (platelet count below 100×109/L) and microangiopathic hemolytic anemia with schistocytes on the blood smear, a negative direct antiglobulin test (Coombs test), elevated levels of hemolysis markers (such as total bilirubin, LDH, free hemoglobin, and an unmeasurable haptoglobin), after exclusion of any other apparent cause. USS can present similar to the following diseases, which have to be excluded: fulminant infections, disseminated intravascular coagulation, autoimmune hemolytic anemia, Evans syndrome, the typical and atypical form of hemolytic uremic syndrome, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, pre-eclampsia, heparin-induced thrombocytopenia, cancer that is often accompanied with metastasis, kidney injury, antiphospholipid antibody syndrome, and side effects from hematopoietic stem cell transplantation.

Uncommon Presentation of Atypical Hemolytic Uremic Syndrome: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal damage. Its presentation as nephrotic syndrome (NS) during first year of life is uncommon; we describe a child with clinical and laboratory findings of NS whose renal biopsy revealed thrombotic microangiopathy (TMA). A previously healthy 4-month-old male was admitted with severe dehydration, diarrhea and anuria. Laboratory results showed electrolyte disturbances, increased serum creatinine, anemia without schistocytes, thrombocytosis, normal lactic dehydrogenase (LDH) levels, hypoalbuminemia hypercholesterolemia and decreased C3 levels. After rehydration hematuria and massive proteinuria were also documented and an initial diagnosis of NS of the first year was established. Studies seeking for infectious agents were negative. During hospitalization he continued to be oligo-anuric needing dialysis and a renal biopsy was performed, which showed TMA findings. We here considered the diagnosis of aHUS and started plasma infusions as a bridge until starting eculizumab. After two infusions urine output improved leading to discontinuation dialysis. The diagnoses of STEC infection and thrombocytopenic thrombotic purpura were ruled out. Factor B, H, I and properdin levels were normal. Antibodies against CFH negative were negative. Screening for genes causative of aHUS detected a heterozygous variant in CFHR3 of uncertain significance. On day 20, treatment was switched to eculizumab, which induced a progressive remission of the NS. This case outlines the need for a heightened diagnosis suspicion of this already rare disease since early initiation of eculizumab therapy improves its prognosis.

[Hemolytic-uremic syndrome and Streptococcus pneumoniae].

Hemolytic-uremic syndrome (HUS) is an uncommon complication of pneumococcal infection. Highly suggesting findings in a patient with Streptococcus pneumoniae infection are: microangyopatic hemolytic anemia, thrombocytopenia and acute renal failure. We report a 41 years old woman, admitted to the hospital due to a severe pneumonia, that required the surgical drainage of an empyema. On admission, a drop in packed red cell volume from 41 to 25%, the presence of schistocytes in the blood smear, an elevation of LDH to 1,700 IU/L, a fall in haptoglobin to 5.8 mg/dL and a thrombocytopenia of 72,000 per mm3 were detected. These alterations coincided with an oliguric acute renal failure. She was treated with hemodialysis and the hemolytic syndrome was managed with plasmapheresis. She was discharged 35 days after admission and in the follow up, after 2.5 months, her serum creatinine is 1.2 mg/dL and her packed red cell volume is 41%.

Hemolytic–uremic syndrome

People with HUS commonly exhibit the symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count), schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally), proteinuria (indicative of kidney injury), confusion, fatigue, swelling, nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and

Thrombotic microangiopathy following Bothrops jararaca snakebite: case report.

Thrombotic microangiopathy (TMA) is an uncommon and severe complication of snakebites, and is similar, in general, to hemolytic-uremic syndrome (HUS). We describe a case of TMA following envenomation by Bothrops jararaca. A 56-y-old-woman with controlled hypertension was transferred from a primary hospital to our ER ∼7 h after being bitten by B. jararaca in the distal left leg. She developed edema extending from the bite site to the proximal thigh, associated with intense radiating local pain, local paresthesia and ecchymosis at the bite site. Laboratory features upon admission revealed coagulopathy (20 min whole blood clotting time - WBCT20 > 20 min), thrombocytopenia (76,000 platelets/mm<sup3</sup) and slight increase in serum creatinine (1.58 mg/dL; RV < 1.2 mg/dL). Upon admission, the patient was treated with bothropic antivenom and fluids replacement. During evolution, her thrombocytopenia and anemia worsened, with blood films showing fragmented red cells, haptoglobin consumption, increase in serum lactate dehydrogenase, and progressive increase of serum creatinine (KDIGO stage = 3). No RBC transfusion, renal replacement therapy or plasmapheresis was done. The patient showed progressive improvement from day nine (D9) onwards and was discharged on D20; there was complete recovery of hemoglobin levels at follow-up (D50). ADAMTS-13 activity, assayed 10 months post-bite, was within reference values. TMA following snakebite has been reported mainly in India, Sri Lanka and Australia, with several patients needing renal replacement therapy. Although controversial, plasmapheresis has also been used in some cases. Our patient developed microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, a triad of features compatible with TMA similar to HUS. Despite the severity, the outcome following conservative treatment was good, with complete recovery.

InternalMed_Harrison

Shiga toxin produced by S. dysenteriae type 1 has been linked countries, where enterohemorrhagic E. coli (EHEC) predominates as the etiologic agent of this syndrome. HUS is an early complication that most often develops after several days of diarrhea. Clinical examination shows pallor, asthenia, and irritability and, in some cases, bleeding of the nose and gums, oliguria, and increasing edema. HUS is a nonimmune (Coombs test–negative) hemolytic anemia defined by a diagnostic triad: microangiopathic hemolytic anemia (hemoglobin level typically <80 g/L [<8 g/dL]), thrombocytopenia (mild to moderate in severity; typically <60,000 platelets/μL), and acute renal failure due to thrombosis of the glomerular capillaries (with markedly elevated creatinine levels). Anemia is severe, with fragmented red blood cells (schizocytes) in the peripheral smear, high serum concentrations of lactate dehydrogenase and free circulating hemoglobin, and elevated reticulocyte counts. Acute renal failure occurs

InternalMed_Harrison

A complete blood count may provide diagnostic clues. Anemia is common in AKI and is usually multifactorial in origin. It is not related to an effect of AKI solely on production of red blood cells because this effect in isolation takes longer to manifest. Peripheral eosinophilia can accompany interstitial nephritis, atheroembolic disease, polyarteritis nodosa, and Churg-Strauss vasculitis. Severe anemia in the absence of bleeding may reflect hemolysis, multiple myeloma, or thrombotic microangiopathy (e.g., HUS or TTP). Other laboratory findings of thrombotic microangiopathy include thrombocytopenia, schistocytes on peripheral blood smear, elevated lactate dehydrogenase level, and low haptoglobin content. Evaluation of patients suspected of having TTP-HUS includes measurement of levels of the von Willebrand factor cleaving protease (ADAMTS13) and testing for Shiga toxin–producing Escherichia coli. “Atypical HUS” constitutes the majority of adult cases of HUS; genetic testing is

Gastrointestinal infection-related disseminated intravascular coagulation mimicking Shiga toxin-mediated hemolytic uremic syndrome - implications of classical clinical indexes in making the diagnosis: A case report and literature review.

Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders or medical interventions. There is overlap between the clinical presentation and pathophysiology of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (HUS), and to a lesser extent, disseminated intravascular coagulation (DIC). We describe a case to illustrate the potential diagnostic difficulty, especially at initial presentation. We reported a case of a 44-year-old woman that presented with diarrhea, thrombocytopenia, schistocytes, elevated serum lactate dehydrogenase (LDH) level and acute kidney injury. While the clinical presentation resembled that of Shiga toxin-induced HUS, the disease course was more consistent with gastrointestinal infection-related DIC. To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing <iEscherichia coli</i (commonly referred to as STEC). The use and correct interpretation of classical indexes of schistocyte, LDH, and platelet count is vital in diagnosing TMA and associated disorders. Understanding the characteristics of these biomarkers in the context of thrombocytopenia purpura, HUS and DIC will facilitate the accurate diagnosis and early initiation of appropriate treatment.

Hemolytic Uremic Syndrome -- Evaluation

The diagnosis of HUS requires a high index of suspicion based on symptoms, travel history, laboratory data, and dietary history. [14] [15] [16] Initial tests should include a complete blood count with differential and comprehensive blood metabolic panel. Elevated LDH and indirect bilirubin, as well as low haptoglobin and elevated plasma hemoglobin, are diagnostic of hemolytic anemia, as are schistocytes on peripheral smear. A Coombs test should be negative, with the exception of HUS caused by S pneumonia .

A case of atypical hemolytic uremic syndrome.

A 9-year-old boy presented with fever not responding to antibiotic therapy and elevated blood urea and serum creatinine levels. The patient developed microangiopathic hemolytic anemia and thrombocytopenia during the hospital stay. Kidney biopsy confirmed the diagnosis of atypical hemolytic uremic syndrome (HUS). The patient had sufficient urine output, normal blood pressure, and no evidence of peripheral edema during the whole course of his disease. Serum levels of anti-Epstein-Barr virus immunoglobulin M was elevated, indicating the possible role of Epstein-Barr virus infection in inducing atypical HUS in this patient. The patient underwent hemodialysis with dramatic response. He was discharged with normal kidney function after a few days. Kidney function and platelet count were normal 12 months after the initial presentation. This case report shows that atypical hemolytic uremic syndrome could have unusual presentations such as the absence of oliguria, hypertension, and edema, with rapid recovery and good prognosis.

Hemolytic uremic syndrome caused by sea anemone sting: a case report.

Some sea anemone toxins cause renal injuries resembling hemolytic uremic syndrome (HUS). To date, only a few cases of HUS caused by sea anemone stings have been reported. In this case report, we have described an HUS case caused by a sea anemone sting. In November 2019, a 37-year-old man with no underlying disease was admitted to our hospital. He presented with intense pain, a rash on, and swelling in his right thigh. Two days prior, he had been stung by a sea anemone while scuba diving in Cebu, Philippines. His blood tests revealed renal dysfunction, and his platelet count was normal. However, on day three, the platelet count decreased rapidly. His blood haptoglobin level decreased, and schistocytes were identified on the peripheral blood smear. We suspected thrombotic microangiopathy and started the conventional treatment, comprising hemodialysis, blood transfusion, and antibiotic administration. ADAMTS-13 and genetic test results associated with atypical HUS were normal. Therefore, the patient was diagnosed with HUS caused by a sea anemone toxin. HUS caused by a sea anemone toxin is rare, but it is a serious medical disease. Clinicians should consider HUS in patients with such clinical presentations, and they should make prompt treatment-related decisions.

[Invasive pneumococcal disease and hemolytic uremic syndrome: new serotype].

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury, in a patient with Streptococcus pneumoniae (Sp) invasive infection. A 2-year-old boy was admitted with pneumonia and empyema. Sp was isolated from blood and pleural fluid cultures. After 72 h, the patient showed paleness, asthenia, respiratory whining and oliguria. Laboratory showed anemia, low platelets, increased blood urea, creatirnina, lactate dehdrogenase, direct Coombs +, schistocytes, fibrinogen, normal coagulogram and increased D-dimer. Proteinuria and hematuria were detected in urine. Mechanical ventilatory assistance and transfusions of washed red blood cells were required. The patient recovered progressively. Sp serotype 38 was isolated in the National Reference Laboratory "Malbran". This is the first report associated to this serotype.

Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab: A case report.

Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA secondary to sepsis- induced coagulopathy, who was successfully treated with eculizumab.A 44-year-old woman, who had no special medical history or familial history of TMAs, was admitted on suspicion of septic shock. Physical examination revealed gangrene on her soles. Blood tests revealed a decreased platelet count, disseminated intravascular coagulation (DIC), renal dysfunction, hemolysis, and infection. Although the coagulation disorder improved with intensive care, the low platelet count, elevated lactate dehydrogenase levels, and renal dysfunction persisted. Our investigations subsequently excluded thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-induced HUS. Plasma exchange only improved lactate dehydrogenase levels. We clinically diagnosed this case as atypical HUS and started eculizumab treatment. The patient's platelet count increased, her renal dysfunction improved, and the gangrene on her feet was ameliorated. The patient was discharged without maintenance dialysis therapy after approximately 3 months. Subsequent tests revealed elevated serum levels of soluble C5b-9, and genetic testing revealed compound heterozygous c.184G > A (Val62Ile) and c.1204T > C (Tyr402His) single-nucleotide polymorphisms in complement factor H.We encountered a case of complement-mediated TMA accompanied by DIC, which was successfully treated with eculizumab. Further studies are necessary to support the optimal use of eculizumab for TMA with background diseases.

InternalMed_Harrison

Microvascular Thrombotic Crisis (Thrombotic Thrombocytopenic Purpura, Hemolytic-Uremic Syndrome) This syndrome of hemolysis, thrombocytopenia, and microvascular thrombosis in kidneys, brain, and other tissues carries a high mortality rate and occurs most commonly in young individuals with lupus nephritis. The most useful laboratory tests are identification of schistocytes on peripheral blood smears, elevated serum levels of lactate dehydrogenase, and antibodies to 2134 ADAMS13. Plasma exchange or extensive plasmapheresis is usually life-saving; most authorities recommend concomitant glucocorticoid therapy; there is no evidence that cytotoxic drugs are effective.

Hemoglobinuria

Causes Acute glomerulonephritis Burns Renal cancer Malaria Paroxysmal nocturnal hemoglobinuria Microangiopathies, e.g. hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP) leading to microangiopathic hemolytic anemia Transfusion reactions IgM autoimmune hemolytic anemia Glucose-6-phosphate dehydrogenase deficiency Pyelonephritis Sickle cell anemia Tuberculosis of the urinary tract March hemoglobinuria secondary to repetitive impacts on the body, usually the feet Athletic nephritis secondary to strenuous exercise Acute lead poisoning Diagnosis The diagnosis is often made based on the medical history, blood samples, and a urine sample. The absence of urine RBCs and RBC casts microscopically despite a positive dipstick test suggests hemoglobinuria or myoglobinuria. The medical term for RBCs in the urine is hematuria. See also Hematuria References External links Abnormal clinical and laboratory findings for urine

Renal thrombotic microangiopathies induced by severe hypertension.

Renal thrombotic microangiopathy (TMA) is an uncommon vascular complication of severe hypertension. Until now, its clinical-pathological characteristics and renal survival have been unclear. Twenty-one patients with biopsy-proven renal TMA and with severe or malignant hypertension were retrospectively studied. All the patients exhibited severe hypertension, with systolic blood pressure at 200-280 mmHg and diastolic pressure at 110-180 mmHg. No patients had hemorrhagic manifestations. Elevated lactate dehydrogenase and thrombocytopenia were found in 6 and 5 patients, respectively. Significant proteinuria (>3 g/day) was present in 2 patients and microscopic hematuria in 18 patients. All patients presented with renal insufficiency (creatinine 3.1+/-2.1 mg/dL). The level of von Willebrand factor:antigen (vWF:Ag) in patients was not significantly higher than that in the healthy subjects, while the ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) activity was not significantly lower than that in the healthy subjects. Renal histology showed a TMA involving preglomerular arterioles and/or interlobular arteries characterized by fibrin deposits and vascular wall sclerosis. Fibrin glomerular microthrombi were not observed in these patients. Four patients required hemodialysis upon admission for severe acute renal failure. On follow-up, 3 patients had recovered normal renal function and 14 had mild renal insufficiency (creatinine 1.8+/-0.3 mg/dL), while 4 patients still required persistent hemodialysis. In conclusion, compared with patients having hemolytic uremic syndrome/thrombocytopenic purpura, our patients showed a low incidence of thrombocytopenia and better renal outcome.