Let's see: a patient with certain history who has: - Schistocytes in smear: indicates microangiopathic anemia, red cell rupture of mechanical cause, which can be seen mainly in PTT, autoimmune hemolytic anemia and DIC. - Bicytopenia: here the causes can be very, very varied. - Elevation of LDH and Bilirubin, which indicates a massive rupture of red blood cells. - Negative direct Coombs' test: essential data, indicating that there is no antibody that sticks to the red blood cells. With these wickers we are going to weave the basket: Answer 1: it cannot be because a hemorrhagic transformation does not give such a brutal elevation of LDH and Cr, in addition to not explaining schistocytosis. Answer 2: urgent plasmapheresis... in case of thrombotic thrombocytopenic purpura, yes; I like this answer because it justifies bicytopenia, since microangiopathic hemolytic anemia is produced by rupture of red blood cells when they are fragmented by ultralong von Willebrand factor multimers in case of deficiency of the ADAMST13 enzyme, resulting in brutal platelet aggregates and the flow cytometer does not count 400 platelets, but a molondron of platelets that form a mass, hence the thrombocytopenia. It also explains the negative direct Coombs, elevated LDH and Cr. Answer 3: a situation as critical as that patient's indicates that something big is going on and I would not sit and wait for glucocorticoids to take effect...and I do not know right now what pathology gives that symptomatology and has that treatment as standard. Answer 4: looking for a trigger for DIC...it would make sense if it were not for the fact that in DIC it is VERY characteristic the consumption of coagulation factors, which is not present in this case. Answer 5: a myeloma does not give schistocytosis nor does it have this symptomatology, they would have to give other data that would support this pathology, such as bone pain and hypercalcemia...

Let's see: a patient with certain history who has: - Schistocytes in smear: indicates microangiopathic anemia, red cell rupture of mechanical cause, which can be seen mainly in PTT, autoimmune hemolytic anemia and DIC. - Bicytopenia: here the causes can be very, very varied. - Elevation of LDH and Bilirubin, which indicates a massive rupture of red blood cells. - Negative direct Coombs' test: essential data, indicating that there is no antibody that sticks to the red blood cells. With these wickers we are going to weave the basket: Answer 1: [HIDDEN] Answer 2: urgent plasmapheresis... in case of thrombotic thrombocytopenic purpura, yes; I like this answer because it justifies bicytopenia, since microangiopathic hemolytic anemia is produced by rupture of red blood cells when they are fragmented by ultralong von Willebrand factor multimers in case of deficiency of the ADAMST13 enzyme, resulting in brutal platelet aggregates and the flow cytometer does not count 400 platelets, but a molondron of platelets that form a mass, hence the thrombocytopenia. It also explains the negative direct Coombs, elevated LDH and Cr. Answer 3: a situation as critical as that patient's indicates that something big is going on and [HIDDEN]...and I do not know right now what pathology gives that symptomatology and has that treatment as standard. Answer 4: [HIDDEN] Answer 5: [HIDDEN]

A 54-year-old man, with a personal history of DM, hypertension and mild chronic renal insufficiency, presented with somnolence and right hemiparesis. Laboratory tests: creatinine 2.3 mg/dl, Hb 10.3 g/dl and platelets 20000 mm3, with normal coagulation. Cranial CT: ischemic lesions with microhemorrhagic necrosis. Subsequently, he began with progressive deterioration of the level of consciousness and increase of Cr, LDH and unconjugated bilirubin. Direct Coombs' test was negative. Schistocytes in smear. In view of the diagnostic suspicion, the following conduct is to be followed:

New cranial CT in the presence of suspected hemorrhagic transformation of ischemic stroke.

Beginning of treatment with glucocorticoids at a dose of 1 mg/kg/day.

Suspected multiple myeloma: bone marrow aspirate.

Incidental Thrombotic Thrombocytopenic Purpura during Acute Ischemic Stroke and Thrombolytic Treatment.

Intravenous tissue plasminogen activator (IV tPA) was shown to be an effective treatment for acute ischemic stroke (AIS). According to stroke guidelines, there is no need to wait for the complete blood count (CBC) and coagulation test results before application of IV alteplase if there is no suspected coagulation disorder. In this study, a patient with AIS and thrombotic thrombocytopenic purpura (TTP) symptoms during thrombolytic treatment was presented. A 33-year-old male patient was admitted at the 2.5th hour of AIS symptoms onset with right hemiparesis and sensorimotor aphasia. Cranial computed tomography (CT) and diffusion magnetic resonance imaging did not reveal any abnormality. In his medical history, the patient did not have any contraindication for thrombolytic treatment. To avoid delays to thrombolytic therapy, blood samples were taken, and after that, IV bolus alteplase treatment was applied. During maintenance treatment, agitation and vomiting developed. The result of blood samples showed less than 26,000 mm<sup3</sup platelet count and maintenance therapy was stopped. In control cranial CT, there was no hemorrhage. In the laboratory examination; anemia, low platelet count; increased indirect bilirubin, lactate dehydrogenase (LDH) levels were found, and fever was 38.4°C. Schistocytes were observed in peripheral blood smear and the patient was diagnosed as TTP. Stroke guidelines recommend not to wait for the results of CBC and coagulation tests before IV tPA treatment in patients who do not have any history of coagulopathy disorder. If possible, before applying IV tPA we may wait for the results of coagulation and CBC tests, keeping in mind the diseaes with high mortality such as TTP.

[A 45-year-old man with peripheral monocytosis and right hemiparesis].

We report a 45-year-old man with monocytosis and right hemiparesis. The patient suffered from an acute myocardial infarction from which he recovered completely when he was 42 years old. One year prior to his death, he was found to have increase in monocyte count (35.5% of leukocytes) in peripheral blood and splenomegaly; he was admitted to the hematology service of our hospital. He was diagnosed as having chronic myelomonocytic leukemia after bone marrow examination. He was treated with radiation therapy with improvement in splenomegaly. In May of 1995, he had fever, anemia, and thrombocytopenia for which he needed daily blood transfusion. In November of 1995, he had an onset of weakness in his right hand, and neurologic consultation was asked for in November 27, 1995. Neurologic examination revealed a chronically ill japanese man in no acute distress. He was alert and not demented. Higher cerebral functions were intact. Cranial nerve examination revealed right facial paresis of the central type. Motor-wise, he was right hemiparetic. Generalized muscle wasting was noted apparently due to the chronic debilitating disease. Deep tendon reflexes were within normal range in the right upper extremity, but were diminished in other areas. Sensation was intact, and no meningeal signs were noted. Pertinent laboratory findings were as follows: Hb 8 g/dl, RBC 238 x 10(4)/microliter, WBC 2,900/microliter (band 1.0%, seg 18.5%, lym 28.0%, mono 44.0%, Baso 2.5%), Plt 13 x 10(4)/microliter, PT 16.6"/10.9", APTT 44.7"/35.0". CSF contained 87 mg/dl of protein, 155 mg/dl of glucose and 2 mononuclear cells/microliter. Bone marrow was slightly hypercellular with mild increase in blast forms. No chromosome abnormality was found. CT and MRI revealed a large mass in the left fronto-parietal region and the meninges showed marked thickening with enhancement after gadolinium-DTPA in MRI. The patient was treated with glycerol and steroid, but the subsequent course was complicated by a seizure, agitation, and pneumonia. He died from respiratory failure on January 13, 1996. The patient was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had chronic myelomonocytic leukemia with infiltration of leukemic cells into meninges and the parenchyme of the cerebrum. Thickening of the dura was thought to be in part a reaction to the subdural hematoma as well as to leukemic cells along the meninges. Postmortem examination revealed hypercellular bone marrow with increase in monocytic cells (more than 20%). The lungs showed pneumonia with scattered old tuberculous lesions. The heart showed an old myocardial infarction in the posterior wall of the left ventricle. The brain showed an old chronic subdural hematoma in the left fronto-temporal region and a cystic mass lesion in the left frontoparietal region. The mass was hypercellular and most of them were monocytes. The dura mater showed reactive thickening without leukemic cell infiltration. It was concluded that this patient had chronic myelomonocytic leukemia with a formation of leukemic mass in the brain. Pathologists thought that the mass was a hematogenous spread. It is rare for chronic myelomonocytic leukemia to form a mass lesion in the brain.

[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.

[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)

[Macrothrombocytopenia with deafness, nephritis, cataract, short small intestine, and double ureter].

A 23 year old female, born in 1957, was diagnosed as having idiopathic thrombocytopenic purpura at the age of 3 and treated with prednisolone during her childhood with no response. On her regular check-up in 1978, facial edema and proteinuria suggested renal disease. The family history was negative for bleeding diathesis or renal disease. Close examination revealed the following: WBC 4,200/microliters without leukocyte inclusions, RBC 3.42 x 10(6)/microliters, Hb 11.7 g/dl. PT 10.6 sec, APTT 28.9 sec. Platelet count 4,500/microliters by HEMATRAK 360, and 40 x 10(3)/microliters measured by microscopic method. Giant platelets were noted on peripheral blood smear with an average diameter of 6.1 microns. Bleeding time (Duke) was 12.0 min. Number of megakaryocytes was increased although platelet production was remarkably decreased. Results of platelet aggregation and retention tests were normal. Platelet life span (T1/2) was 2.3 days. Sensory neural hearing loss, congenital cataract, double ureter and short small intestine were also found. Chromosome analysis showed 46XX. She underwent splenectomy resulting in increase of the platelet count to 226 x 10(3)/microliters. The increased platelet count, however, gradually decreased to the initial count in 2 years although the bleeding tendency was improved. In 1987, renal function deteriorated, causing intractable hypertension. The serum creatinine was 4.8 mg/dl. The following year she developed cerebral bleeding and died 4 days after the episode. The serum creatinine was 8.6 mg/dl.

[(Neurological CPC-59). A 65-year-old man with a history of gastric cancer who presented progressive loss of vision, memory loss and consciousness disturbance].

We report a 65-year-old man with progressive loss of vision and consciousness disturbance. The patient was well until his age of 63 when he was found to have a gastric cancer. He was treated by the tumor resection and chemotherapy; he was apparently well, but hepatic metastases were found in the next year (1996). In June, 1996, he noted an onset of blurred vision more on the left. He was admitted to the ophthalmology service of our hospital on July 14, 1996. His vision was 0.8 on the right and 0.15 on the left. He was treated with oral prednisolone with slight improvement. He was also found to have IgM kappa-type monoclonal gammopathy; Bence-Jones protein was positive and a bone marrow aspiration revealed that approximately 10% of bone marrow cells were atypical plasma cells. His vision had progressively got worse and he became blind by the end of October 1996. A chest X-ray and cranial CT scan revealed multiple abnormal nodular densities. In the middle of November 1996, he became confused, disoriented and agitated. His mental symptoms had progressively became worse, and a neurologic consultation was asked on December 10, 1996. Neurologic examination revealed that he was somnolent with decreased attention to his surroundings. He showed marked disorientation and memory loss. Higher cerebral functions appeared intact. He was able to recognize only light and dark. Pupils were moderately dilated with very sluggish light reflex remained. Vertical gaze was moderately restricted and horizontal nystagmus was noted upon left and right lateral gaze. The remaining of the neurologic examination were unremarkable. General physical examination revealed hepatosplenomegaly; the liver was palpable by 3 cm below the right costal margin. Laboratory examination revealed anemia (Hb10.1 g/dl) and thrombocytopenia (43,000/microliter). A cranial CT scan and MRI revealed a mass lesion in involving the chiasmatic and bilateral hypothalamic areas. The tumor showed intense homogeneous enhancement after Gd-DTPA infusion. The patient was treated with dexamethasone and radiation. After 9 Gray radiation, he showed deterioration in the sensorium; a cranial CT scan revealed a hydrocephalus of the right ventricle with the midline shift towards left. The radiation was discontinued. The subsequent clinical course was complicated by aspiration pneumonia and thrombocytopenia. He expired on January 4, 1997. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had systemic malignant lymphoma with metastasis to the brain judging from the characteristics of MRI and CT findings. Opinions were divided between malignant lymphoma and metastatic brain tumor. Post-mortem examination revealed plasmacytoid lymphocytic infiltration in the bone marrow. Immunologically, these cells were positive for IgM and kappa-type light chain. These plasmacytic infiltrations were seen in the lungs and lymph nodes. These findings were consistent with the diagnosis of Waldenström's macroglobulinemia. In the liver metastatic cancer tissues were seen; microscopic pictures were essentially similar to those of resected gastric cancer. No local recidive was noted in the stomach. In the central nervous system, a necrotic tissue was involving the hypothalamic area bilaterally; no clear neoplastic cells were found, however, lymphocytic and plasmacytic infiltrations were seen in the perivascular space. In the optic nerves, loss of myelin and axons were seen. These findings most likely mass formation from macroglobulinemia which underwent necrotic change after radiation. Mass formation in the brain is rare for Waldenström's macroglobulinemia, although it has been reported. The relation between gastric cancer and macroglobulinemia in this patient is unclear.

[Autopsy case of dural thickening caused by widespread dural vein thrombosis associated with disseminated bone marrow carcinomatosis].

A 64-year-old woman was referred to our hospital because of disturbance of consciousness. She had undergone distal gastrectomy for gastric carcinoma 17 years previously. General physical examination was unremarkable, neurologic examination disclosed hyperactive deep tendon reflexes in the upper limbs. Laboratory abnormalities included elevations of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and findings suggesting disseminated intravascular coagulation (DIC). Lumbar cerebrospinal fluid showed a protein concentration of 408 mg/dl and a glucose concentration of 82 mg/dl (blood: 110 mg/dl), as well as a cell count of 16/mm3. Cranial computed tomography indicated brain edema. Magnetic resonance imaging (MRI) of the brain showed diffuse thickening of the dura mater, with contrast enhancement upon gadolinium-DTPA administration. These findings suggested hypertrophic pachymeningitis. Magnetic resonance venography (MRV) showed occlusion of the left transverse sinus and attenuation of the straight sinus. MRI of the spine as well as gallium scintigrams demonstrated multiple areas of increased uptake in areas near the skull and spine. We therefore suspected tumor metastasis. The patient was given heparin as well as pulse therapy with methylprednisolone, but she died 7 weeks after symptom onset. At postmortem examination, the dura was thickened. Histopathologically, numerous tumor cell emboli in the dura were confined to the lumens of veins. The tumor cells were thought to have metastasized to the dura through the vertebral venous plexus (Batson's plexus). Immunostaining demonstrated immunoreactivity of tumor cells to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The primary origin of the carcinoma was not precisely identified by these findings. Widespread dural vein tumor emboli should be taken into consideration as a cause in cases that develop rapid deterioration of consciousness associated dura mater thickening.

[Ticlopidine-associated thrombotic thrombocytopenic purpura (Morbus Moschcowitz)].

A 75-year-old woman with a history of recurrent ischemic cerebral events was admitted with acute unspecific neurological symptoms and fever. Intracerebral hemorrhage due to hypertension and antithrombotic therapy with ticlopidine was ruled out with cranial computed tomography. Laboratory findings on admission included thrombocytopenia (12/nl), renal insufficiency (serum creatinine 1.6 mg/dl) and LDH elevation (1,218 U/l). The hemoglobin on admission was normal. In the presence of rapidly declining hemoglobin values and fragmentation of red cells thrombotic-thrombocytopenic purpura (TTP) was diagnosed and the patient received fresh frozen plasma. Shortly after the plasma infusion the patient's condition deteriorated rapidly showing clinical signs of an allergic shock. In the sequel of 24 to 48 hours the patient developed renal failure, severe anemia and the thrombocyte count fell to 5/nl. The patient was mechanically ventilated during the next 48 hours and needed intravenous catecholamines. Even after restoration of spontaneous respiration and cessation of pharmacological sedation the patient remained comatose. Cranial computed tomography on the fourth day after admission showed multiple infarction syndrome. The patient died on the ninth day after admission in status epilepticus which could not be stopped with pharmacological means. The combination of neurological symptoms, thrombocytopenia, fever, renal failure and hemolytic anemia in a patient taking ticlopidine points to a diagnosis of TTP. The high mortality of TTP can probably only be reduced by early plasmapheresis.

Thrombotic microangiopathy

Diagnosis CBC and blood film: decreased platelets and schistocytes PT, aPTT, fibrinogen: normal markers of hemolysis: increased unconjugated bilirubin, increased LDH, decreased haptoglobin negative Coombs test. Creatinine, urea, to follow renal function ADAMSTS-13 gene, activity or inhibitor testing (TTP).

[A 36-year-old woman with acute onset left hemiplegia and anosognosia].

We report a 36-year-old woman with right hemiplegia, anosognosia, and rapidly deteriorating course. She was well until the end of January, 1995 when she had an onset of fever, sputum, and cough. A 5 x 5 tumor was found in her left lower lobe. She was admitted to the Pulmonary Medicine on May 24, 1995 when she was 36-year-old. General physical examination was unremarkable. Bone scintigraphy revealed increased uptake in the skull, sternum, right scapula, vertebrae, right femur, and in ribs. Cranial CT scan revealed a large mass lesion in the right frontal subcortical region with central low density and peripheral high density areas, and small low density lesions in the right thalamic area and in the right posterior frontal region; ring enhancement was observed in the latter two lesions. On the second day of admission, she noted left-sided weakness which improved by corticosteroid treatment. On June 17, there was a sudden onset of left hemiparesis and a neurologic consultation was asked. Upon neurologic examination, she appeared somnolent but could understand verbal commands. She showed constructional apraxia, neglect of the left hemisphere, and anosognosia. Cranial nerves were unremarkable. Motor-wise, she showed flaccid left hemiplegia. Deep tendon reflexes were exaggerated on the left and the plantar response was extensor bilaterally. Nuchal stiffness was noted. Her cranial CT scan on June 17 revealed enlargement of the right frontal mass lesion. The subsequent course was complicated by DIC and progressive worsening of her consciousness. On June 18, she was comatose and pupillary light reflex was lost. She developed Cheyne-Stokes respiration and expired on that evening. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had a primary adenocarcinoma in the lung with multiple metastases including the brain. The fulminant terminal course was ascribed to hemorrhage within the tumor and subsequent central type of transtentorial herniation. Opinions were divided regarding the cause of hemorrhage; some participants thought hemorrhage was caused by DIC. Post-mortem examination revealed an adenocarcinoma arising at the S6 segment of the left lung with multiple organ metastases. In the brain, a huge hemorrhagic metastasis was found in the right frontal lobe and a non-hemorrhagic metastasis in the right thalamic region. Probably, the size of the metastases influenced the occurrence of hemorrhage. The direct cause of the death was transtentorial herniation.

InternalMed_Harrison

TTP is a devastating disease if not diagnosed and treated promptly. In patients presenting with new thrombocytopenia, with or without evidence of renal insufficiency and other elements of classic TTP, laboratory data should be obtained to rule out DIC and to evaluate for evidence of microangiopathic hemolytic anemia. Findings to support the TTP diagnosis include an increased lactate dehydrogenase and indirect bilirubin, decreased haptoglobin, and increased reticulocyte count, with a negative direct antiglobulin test. The peripheral smear should be examined for evidence of schistocytes (Fig. 140-1D). Polychromasia is usually also present due to the increased number of young red blood cells, and nucleated RBCs are often present, which is thought to be due to infarction in the micro-circulatory system of the bone marrow.

[A case of acute renal and liver dysfunction with light chain deposition disease].

A 62 year old woman was referred to our hospital because of acute renal and liver dysfunction. Prior to admission, she had already been started on hemodyalysis filtration(HDF). She showed facial edema and lumbar pain caused by an Ll compressive fracture. Laboratory examinations revealed hypercalcemia (13.2 mg/dL), hyperammonemia (297 microg/dL) and her serum creatinine, blood urea nitrogen and total bilirubin levels were 3.9 mg/dL, 37.4 mg/dL and 3.2 mg/dL, respectively. Among the components of immunoglobulin, IgA was increased, while IgG and IgM were decreased. Serum immunoelectrophoresis revealed the presence of the IgA kappa type of M component. Punched out lesions were noted on her head radiography. Severe plasmacytosis (60-70 % of total cells) were observed by a bone marrow aspiration test, indicating the diagnosis of multiple myeloma. Steroid pulse therapy was started with dexamethasone (40 mg/day, 3 days), and plasma exchange was performed 8 times with continuous HDF. These treatments failed to control hemodynamics and she died of disseminated intravascular coagulation (DIC). Autopsy demonstrated amyloid-like depositions in perisinusoidal space in the liver. In the kidney, there were nodular lesions in the glomeruli, and depositions in the basement membrane of the uriniferous tubuli. Congo red staining of these organs for amyloid yielded negative results. Immunohistochemical staining gave positive results for IgA and kappa. Electron microscopy revealed granular electron deposits in the glomeruli and tubular basement membrane as well. Taken altogether, the diagnosis of the patient could be light chain deposition disease (LCDD).

Quetiapine-induced thrombotic microangiopathy in a patient on maintenance dialysis.

Quetiapine has been reported to cause immune-mediated thrombotic microangiopathy (TMA), although few cases have been reported thus far. A 71-year-old man with autosomal dominant polycystic kidney disease on maintenance dialysis was hospitalized with a hemorrhagic basal ganglia stroke, and was treated with 25 mg quetiapine for delirium from day 4 of admission. There was no worsening of consciousness, fever, diarrhea, or elevated blood pressure during the hospitalization. Gingival bleeding appeared on day 35, and the platelet count on day 38 was 0.5 × 10<sup4</sup/μL (13.2 × 10<sup4</sup/μL on day 16). The presence of 1% schistocytes, high LDH level, inability to measure haptoglobin, negative direct Coombs test, and normal prothrombin time and activated partial thromboplastin time indicated TMA. We considered an exclusionary diagnosis of drug-induced TMA, because of normal ADAMTS13 activity, no evidence of complement activation and the absence of Shiga toxin or symptoms of collagen disease or cancer. Quetiapine was the most likely causative factor; however, all drugs, including heparin, were discontinued or changed. Due to persistent microbleeding, platelet transfusions were performed several times. After only quetiapine was discontinued, the platelet count recovered smoothly to 3.1 and 7.2 × 10<sup4</sup/μL on days 45 and 72, respectively; LDH and fibrinogen levels normalized on day 47. All medications, except quetiapine, were restarted sequentially after day 47, without subsequent thrombocytopenia. Platelet activation predominantly by a drug-dependent antibody might be the etiology of quetiapine-induced TMA. Plasmapheresis may not be necessary for quetiapine, because of its unproven efficacy in drug-induced TMA.

InternalMed_Harrison

The mortality ranges from 30 to >80% depending on the underlying disease, the severity of the DIC, and the age of the patient. The diagnosis of clinically significant DIC is based on the presence of clinical and/or laboratory abnormalities of coagulation or thrombocytopenia. The laboratory diagnosis of DIC should prompt a search for the underlying disease if it is not already apparent. There is no single test that establishes the diagnosis of DIC. The laboratory investigation should include coagulation tests (aPTT, PT, thrombin time [TT]) and markers of fibrin degradation products (FDPs), in addition to platelet and red cell count and analysis of the blood smear. These tests should be repeated over a period of 6–8 h because an initially mild abnormality can change dramatically in patients with severe DIC.

Multiple myeloma

Signs and symptoms Because many organs can be affected by myeloma, the symptoms and signs vary greatly. Fatigue and bone pain are the most common symptoms at presentation. The CRAB criteria encompass the most common signs of multiple myeloma: Calcium: serum calcium >0.25 mmol/l (>1 mg/dl) higher than the upper limit of normal or >2.75 mmol/l (>11 mg/dl) Renal insufficiency: creatinine clearance <40 ml per minute or serum creatinine >1.77 mol/l (>2 mg/dl) Anemia: hemoglobin value of >2g/dl below the lowest limit of normal, or a hemoglobin value <10g/dl Bone lesions: osteolytic lesions on skeletal radiography, CT, or PET/CT Bone pain

[Sudden death associated with myocardial damage caused by microthrombi in a patient with thrombotic thrombocytopenic purpura].

We describe a 35-year-old woman with Down's syndrome who was admitted to a clinic with anorexia and vomiting. Since laboratory findings showed anemia (Hb 7.4 g/dl) and thrombocytopenia (0.5 × 10⁴/μl), she was transferred to our hospital for treatment. Further laboratory examinations revealed schistocytes, LDH elevation, and a negative Coombs' test. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange (PEX) and prednisolone administration were thus immediately initiated. Prior to these treatments, ADAMTS13 activity was less than 5% and inhibitors were detected at a level of 0.8 Bethesda U/ml. Although her platelet count had risen to 13.0 × 10⁴/μl by day 6 (post 4 sessions of PEX), it had decreased to 1.8 × 10⁴/μl on day 7. Despite ongoing PEX, thrombocytopenia persisted. On day 21, she suddenly died. Autopsy findings revealed no evidence of myocardial necrosis or coronary artery thrombosis. Extensive microthrombi were, however, detected in precapillary arterioles, capillaries, and post-capillary venules of the heart. Therefore, this patient's sudden death was clinically suspected to have been caused by cardiomyopathy, which had produced cardiogenic shock.

[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.

[A 91-year-old man with a stroke, hypertension, and renal failure].

We report a 91-year-old man who had a stroke and died of renal failure. He had been treated for hypertension since 20 years before the onset of the present illness. In addition, he was operated on a gastric cancer 17 years previously. Otherwise he was doing well until May 29, 1991 (when he was 87-year-old) when he had sudden onset of dysarthria and right facial weakness. He was admitted to our hospital. On admission, general physical examination was unremarkable, and neurologic examination revealed a mentally sound man with slight dysarthria, right facial weakness, orolingual dyskinesia, and dysequilibrium in which he showed difficulty in tandem gait; however, no cerebellar ataxia was noted. A cranial CT scan revealed leukoaraiosis with multiple low density areas in the cerebral white matter. His BUN was 37 mg/dl and Cr 2.2 mg/dl. His neurologic symptoms cleared within the next few weeks and he was discharged with ticlopidine 100 mg q.d.. He had been doing well after the discharge except for gradual worsening of his renal function; his BUN was 65 mg/dl and Cr 3.27 mg/dl in April of 1994. On March 10, 1995, he fell down and hit his back; he became unable to walk because of pain, and he was admitted again on March 16, 1995. On admission, his blood pressure was 170/80 mmHg. There was an 1 + pitting pretibial edema; otherwise general physical examination was unremarkable. Neurologic examination revealed an alert and oriented man, however, Hasegawa's dementia scale was 23/30. Higher cerebral functions as well as cranial nerves were intact. He showed some unsteadiness of gait, however, no motor weakness or ataxia was noted. Deep tendon reflexes were diminished, but Chaddock sign was positive bilaterally. Vibration was diminished in the feet, however, pain and touch sensations were intact. Laboratory examination revealed a compression fracture of the twelfth thoracic vertebra. Blood count and chemistries were as follows; Hb 7.6 g/dl, Hct 23.3%, TP 6.0 g/dl, Alb 3.6 g/dl, BUN 87 mg/dl, Cr 4.53 mg/dl, T-Chol 174 mg/dl, HDL-Chol 49 mg/dl, Glu 156 mg/dl, Na 142 mEq/L, K 5.4 mEq/L, Cl 115 mEq/L. A urine specimen contained 1 + protein and 1 + glucose, and the sediments contained hyaline casts. A cranial CT scan was essentially same as that taken four years ago. His hospital course was complicated with pneumonia, congestive heart failure, and progressive renal failure. He was treated with intravenous fluid, chemotherapy, and other supportive measures, however, he expired from respiratory failure on April 30, 1995. He was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had Binswanger's disease in the brain, benign nephrosclerosis from arteriolosclerosis due to hypertension, congestive heart failure, and pneumonia. Opinions were divided regarding the question as to whether or not this patient had Binswanger's disease. Although his cranial CT scan revealed leukoaraiosis, his dementia and gait disturbance was only mild until his fall on March, 1995. Clinical features did not conform to those of Binswanger's disease. Postmortem examination of the right hemisphere revealed wide spread atherosclerosis and arteriolosclerosis. The kidney showed benign nephrosclerosis due to arteriolosclerosis. Sclerotic changes were also seen in the coronary arteries and the left middle cerebral artery with 70% stenosis. Myelin stain showed diffuse myelin pallor of the cerebral white matters with scattered small infarcts. Arterioles in the white matter showed arteriolosclerosis. Small infarcts were also seen in the putamen and in the thalamus. This patient appeared to have had circulatory disturbance of the white matter which is the basic abnormality causing Binswanger's disease. However, white matter changes in this patient were not quite severe enough to make a pathologic diagnosis of Binswanger's disease.

[Clinical profile and course of paroxysmal nocturnal hemoglobinuria].

To evaluate the clinical characteristics, laboratory findings, course, treatment and survival of a series of patients with PNH. The clinical records of 21 patients diagnosed of PNH in the La Fe University Hospital between 1970 and July 1991 were revised. Positivity to Ham's and sucrose tests was the major diagnostic criterion. Haemolysis was studied by means of reticulocyte count, unconjugated bilirubin, LDH levels, haptoglobin, serum iron, and haemosiderinuria. The survival analysis was performed in accordance with Kaplan and Meier. The median age in the group was 38 years (range: 18-72 years) and the M/F ratio was 11/10. The commonest symptoms at onset were weakness (76%), dark urine (47%), jaundice (33%), and purpura (24%). All the patients had anaemia, six of them (28%) presenting with aplastic anaemia. The complications most frequently seen included thrombosis (documented in 7 cases, clinically suspected in 6 others), infection (6 cases) and haemorrhage (6 cases). One patient developed aplastic anaemia after 16 years of follow-up, and another one had AML. None of the patients with PNH-associated aplastic anaemia developed thrombosis. The incidence of severe cytopenia was: Hb < 80 g/L, 62%; platelet count < or = 20 x 10(9)/L, 29%, and white cell count < or = 2 x 10(9)/L, 14%. The haemolysis-related findings were as follows: unconjugated hyperbilirubinemia, 100%; haemosiderinuria, 87%; decreased haptoglobin, 80%. Transfusion support consisted of washed red cells (total amount, 1,684 units) and platelets (137 units). A female patient with anticoagulant therapy developed haemolysis after non-isogroup plasma transfusion. Five patients required no transfusions. One patient was subjected to splenectomy and other underwent a successful bone-marrow transplant. The cause of death was related to PNH in three of the five patients who had died when this study was finished (mesenteric thrombosis, subcapsular haematoma of the liver and AML). The actuarial survival at 10 years was 68%. 1) The incidence of PNH is very low in our experience, excessive delay in diagnosis being the rule, as in other reported series. 2) Early anti-thrombotic treatment should be carried out in PNH whenever severe thrombocytopenia is not associated. 3) Allogeneic BMT is the only curative treatment.

Subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome successfully treated with cyclosporin A.

A 17-year-old girl previously in good health presented with a 2-month history of recurrent, high-grade fever; general fatigue; anorexia; a 10-kg weight loss; and multiple, painful, reddish skin lesions on the lower abdomen. Some lesions were ulcerated, with an oily yellowish brown discharge. A systemic review was unremarkable other than bleeding from the nose. Her medical and family histories were unremarkable. On examination, the patient was pale, jaundiced, and febrile (temperature of 39 degrees C). She had enlarged lymph nodes in the axillary and inguinal areas. There was moderate hepatosplenomegaly. Local skin examination revealed multiple erythematous, tender, and firm subcutaneous nodules of variable size (1-2 cm) on the lower abdomen. Some nodules were ulcerated, with oily yellowish brown discharge and overlying ecchymosis (Figures 1 and 2). Mucous membranes were free of lesions. Laboratory investigations showed pancytopenia, an elevated erythrocyte sedimentation rate (>80 mm/h), normal renal function tests, abnormal hepatic function tests (alanine aminotransferase 172 U/L, aspartate aminotransferase 229 U/L, alkaline phosphatase 725 U/L, and total bilirubin 100 mmol/L [normal range 0-18 mmol/L]), conjugated bilirubin 45 mmol/L (normal range 0-5 mmol/L), and high triglycerides 855 mg/dL (normal range 20-200 mg/dL). Prolonged prothrombin time, 26 seconds (normal range 13-16 seconds); prolonged activated partial thromboplastin time, 61 seconds (normal range 26-38 seconds); positive disseminated intravascular coagulation studies evidenced by low fibrinogen, 74 mg/dL (normal range 160-350 mg/dL); and positive fibrinogen degradation products were also noted. Throat, midstream urine, and blood culture results were negative. Serologic tests for syphilis, HIV, and hepatitis B and C viruses were negative. Epstein-Barr virus and cytomegalovirus serologic values revealed evidence of past infection. Tuberculin and Coombs tests were negative. The alpha1-antitrypsin level was normal. Antinuclear and anti-smith antibodies, rheumatoid factor, and cryoglobulins were negative. CT showed enlarged lymph nodes in the axillary and inguinal areas, bilateral small pleural effusion, moderate hepatosplenomegaly, severe fatty infiltration of the liver, and thickening of lower abdominal subcutaneous tissue. A liver biopsy showed steatohepatitis. Bone marrow aspirate and trephine were normal. A deep punch biopsy of a nodule from the right lower abdomen revealed lobular panniculitis with atypical lymphocytes and large macrophages with cytophagocytosis ("beanbag" cells) (Figures 3 and 4). Immunohistochemistry showed that these atypical cells were positive for CD3, CD8, granzyme B, and perforin, and negative for CD56. T-cell gene rearrangement studies on skin lesions revealed a monoclonal T-cell receptor (gamma-chain) gene rearrangement, supporting the diagnosis of subcutaneous panniculitis-like T-cell lymphoma. On presentation, the initial treatment included 6 U of fresh frozen plasma, 2 U of packed red blood cells, and 2 g IV fibrinogen for 3 consecutive days. The patient was started on prednisolone 60 mg orally once daily and cyclosporine A 5 mg/kg/d orally in two divided doses. The fever and other systemic symptoms and skin lesions resolved within 2 weeks after the treatment. The prednisolone dose was tapered gradually, and a maintenance dose of cyclosporine A was continued. The patient's condition remained in remission at 12-month follow-up; there was no evidence of clinical relapse.

[A 49-year-old man with progressive dysarthria, dysphagia, and left hemiparesis].

We report a 49-year-old man who presented progressive dysarthria, dysphagia, and left hemiparesis. The patient was well until June 28th of 1993 when he noted 'weakness' in his both legs; despite his weakness, he could play golf on that day. In the beginning of July, he noted difficulty in swallowing solid foods. He was admitted to the neurosurgery service of our hospital on July 15th of 1993 and a neurologic consultation was asked on July 17th. Neurologic examination at that time revealed an alert but somewhat childish man who appeared to have some difficulty in paying attention to questions. He was disoriented to time and showed difficulty in recent memory and calculation. Higher cerebral functions were intact. The optic fundi were normal; pupils were isocoric and reacted to light promptly; ocular movements were intact, however, he showed difficulty in convergence. Facial sensation and facial muscles were intact. He had no deafness. He showed slurred speech and difficulty in swallowing solid foods. The remaining cranial nerves were intact. Motor-wise, he was able to walk normally and no weakness or atrophy was noted. Mild ataxia was noted in the finger-to-nose and the heel-to-knee test on the left. Muscle stretch reflexes were normal and symmetric, however, the plantar response was extensor bilaterally. Sensation was intact and no meningeal signs were noted. General routine laboratory findings were unremarkable. CSF was under a normal pressure containing 1 cell/microliter, 68 mg/dl of protein, and 54 mg/dl of glucose. Cranial CT scan showed low density areas involving the pons, midbrain, left thalamus, and the left parietal cortex. In MRI, these areas presented low signal intensity in T1-weighted images and high signal intensity in T2-weighted in images. The brain stem appeared swollen. Gadolinium enhancement was negative. He was given a course of steroid pulse with 1 g/day of DIV methylprednisolone for three days followed by oral steroid. He showed only temporary improvement in swallowing. In the subsequent course, he showed progressive deterioration in dysarthria and dysphagia. A biopsy was performed on the left parietal lobe lesion. After biopsy, he was treated with steroid and glycerol without improvement. A course of chemotherapy with procarbazine, MCNU, and vincristine was given; he did not respond to chemotherapy. His left hemiparesis deteriorated. He developed aspiration pneumonia from dysphagia and expired on October 22, 1993. The patient was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had astrocytoma grade III involving the pons, midbrain, thalamus, and the parietal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

[Proceedings of the 7th Congress of Internal Medicine].

Hemostasis was studied in 55 patients with myeloma, grouped in three groups according to the clinical stage of the disease. Thrombocytic adhesion, aggregation, activity of TF3 and TF4, of antithrombin III, FMDC level, FDP titre and fibrinolysis test were determined on the background of the screening coagulation tests. The studies were carried out before the treatment and were followed up after the therapeutic response or in the absence of improvement. Thirty per cent of the patients had manifestations of hemorrhagic diathesis, and 5 per cent - thromboembolism. Essential hemostatic deviations were found: progressive thrombocytopenia and thrombopathia and DIC syndrome that correlate with the stage of the disease, being most severe among the stage III patients. The patients that responded to the treatment had a great part of the hemostatic disorders corrected, and in case of no effect from the treatment - the deviations persisted, intensified and in 5 of the patients were responsible for the fatal end. The pathogenesis of the hemostatic deviations is complex and is associated with the characteristics of the basic disease and the concomitant complications.

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.

[Critical study of microscopic hematuria disclosed by screening tests].

Asymptomatic microscopic haematuria detected by dipstick in 0.28 p. 100 of 95,200 men was confirmed in only 0.11 p. 100. These results lead to the study of 272 cases to determine the value of dipsticks as a screening test and the benefits of complementary investigations to exclude symptomless diseases. Microscopic haematuria was confirmed in 65 p. 100 but results of other tests reduce the false positive screening results to 25.3 p. 100. Addis counting of at least 5,000 RBC/min is preferable to RBC count/ml which is dilution dependent. 77 p. 100 of microscopic haematuria are intermittent and can only be diagnosed by repeated Addis counts. In the absence of confirmed haematuria, only investigations to exclude proteinuria and urinary infections are justified.

Management of Frail Older Adults with Newly Diagnosed Multiple Myeloma - Moving Toward a Personalized Approach.

A 75-year-old male undergoes an evaluation for progressively worsening fatigue with associated shortness of breath. He also reports back pain worse at night, which does not resolve with acetaminophen. He is retired, but over the past 2 months he is unable to garden or perform household chores. Due to his pain and fatigue, he has limited his activity. He currently takes 9 prescription medications for chronic medical conditions, which include diabetes mellitus with neuropathy, hypertension, hyperlipidemia, and COPD. Initial evaluation reveals anemia (Hgb 9.0 g/dl last known normal was 2 years ago, Hgb 13.5 g/dl), renal impairment (serum creatinine 2.5 mg/dL), hypercalcemia (11.5 g/dl). Plain X-rays reveal compression fractures involving T3 and T4. Multiple myeloma is suspected, further labs confirm the diagnosis of IgG kappa multiple myeloma. LDH is elevated, beta-2-microglobulin is elevated at 6.1 mg/L and albumin < 3.5 mg/dl. Bone marrow aspiration and biopsy reveal plasmacytosis of 55% and on fluorescence in situ hybridization testing, del 17p/TP53 mutation in 85% of cells is detected. PET/CT confirms diffuse bone disease involving the axial and appendicular skeleton. His Karnofsky performance status (KPS) is 70%. He is widowed and lives alone but has 2 adult children who currently live out of state. This abstract will discuss how assessments of fitness/frailty may be used to develop personalized care tailored to the unique needs of older frail adults with multiple myeloma.

Oxcarbazepine-induced hemolytic anemia in a geriatric patient.

Oxcarbazepine is a commonly used antiepileptic and mood stabilizer medication with a considerably good safety profile. Medication-induced side effects are a common cause of morbidity in the geriatric population. We describe a patient presenting with hemolytic anemia attributed to oxcarbazepine that resolved after discontinuation of the drug. A 75-year-old male was brought into the hospital because of lethargy for the previous few days. His medical history included diet-controlled diabetes mellitus, mild essential hypertension, ischemic stroke with no residual deficit, seizure disorder, and dementia. He was taking only trileptal for the previous 3 months. His other history was insignificant. Physical examination was remarkable for generalized pallor and impaired memory. Laboratory results showed hemoglobin of 4.6 g/dL. Serum lactate dehydrogenase was 1314 u/L, and total bilirubin was 3.4 mg/dL, with indirect bilirubin of 2.9 mg/dL. Peripheral blood smear revealed microspherocytes, polychromasia, and a few nucleated red blood cells. Urinalysis showed 12RBCs/high power field (HPF), hemosiderinuria, and moderate bilirubin. Coombs test, cold agglutinins, antinuclear antibodies, and cultures were negative. Computerized tomographic scan of the chest, abdomen, and pelvis was also normal. After exclusion of other causes of hemolysis, drug-induced hemolytic anemia was suspected, and oxcarbazepine was discontinued. The patient's symptoms and laboratory parameters improved. He was in a usual state of health at 7 months follow-up. To our knowledge, this is the first reported case of oxcarbazepine-induced hemolytic anemia in the medical literature, and it was reported to the manufacturing pharmaceutical company.

[Clinicopathological study of miliary tuberculosis in patients with hematologic disease].

Seven cases of miliary tuberculosis in patients with hematologic disease were analyzed clinicopathologically. Mean age of the patients was 65 years, and the hematologic diseases were CML, AML, ALL, MDS and malignant lymphoma. Diabetes mellitus was present as a complication in three patients. Miliary tuberculosis was found in 5 cases during the first admission to our hospital owing to hematologic problems. In 4 of 6 cases, fever had started more than two months before admission, consequently, the tuberculosis probably began about that time. After admission, chemotherapy was administered in 5 cases, and steroid in 6 cases for hematologic disease. The mean total quantity of steroid administered was 2,134 mg of prednisolone and average treatment duration was 69 days. The chest roentgenographic shadow was so atypical that miliary tuberculosis was suspected in only one case. The initial chest roentgenogram showed hilar and mediastinal lymph node swelling as well as the shadow of pulmonary tuberculosis in two cases. It was thought that the hilar and mediastinal lymph node swelling could be explained by primary complex, although the patients were of advanced age, or by "secondary complex" reported by Terplan, K in 1940. The diagnosis of tuberculosis was made in two patients before their death by smear of aspirated fluid of cervical lymph node and by bone marrow cell block in one patients, and by pathological examination of mediastinal lymph node biopsy in the other patients. Tubercles were found from bone marrow cell block in 2 out of 5 patients and from bone marrow biopsy in 1 out of 3 patients, but the positive results were reported in 2 patients following death. Smears of sputum, gastric juice, urine, spinal fluid and pleural effusion were negative in all cases. One patient diagnosed as miliary tuberculosis also had pneumocystis carinii pneumonia. This case was treated with antituberculosis drugs for 20 days without improvement. Another patient diagnosed as miliary tuberculosis improved under treatment with antituberculosis drugs, but died of cytomegalovirus pneumonia. Autopsy in 5 cases revealed non-reactive miliary tuberculosis, and pulmonary hemorrhage probably due to DIC was present as a complication in two cases. In these cases, severe immunosuppression, which is a major precipitating factor of miliary tuberculosis, is thought to be induced by hematologic disease itself, chemotherapy, steroid or other underlying disease such as diabetes mellitus. Miliary tuberculosis in such compromised host is cryptic and progresses rapidly. Consequently, early diagnosis is very important. Retrospectively, the unexplained pyrexia was most important to suspect tuberculosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Multiple Myeloma -- Evaluation

Historically, we have diagnosed MM if clonal bone marrow plasma cells were greater than or equal than 10% on bone marrow biopsy (or if a biopsy-proven plasmacytoma was present) in addition to at least one of the following CRAB criteria: Serum calcium level greater than 0.25 mmol/L (greater than 1 mg/dL) higher than the upper limit of normal or greater than 2.75 mmol/L (greater than 11 mg/dL) Renal insufficiency (creatinine greater than 2 mg/dL [greater than 177 micromol/L] or creatinine clearance less than 40 mL per minute) Anemia (hemoglobin less than 10 g/dL or hemoglobin greater than 2 g/dL below the lower limit of normal) One or more osteolytic bone lesions on skeletal radiography, CT, or PET-CT often described as punched-out, round, radiolucent lesions

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.

[A case report of acute leukemia following the onset of cerebral sinus thrombosis].

A case was reported in which the patient, whose leukemic cells were not found in the peripheral blood, died several days after the onset of cerebral sinus thrombosis, and after the autopsy acute leukemia was diagnosed. The patient, a 68-year-old female, was admitted with clouding of the consciousness. In the initial examination, she was semicomatose, pendulum-like movement was seen in the eyeballs, and hemorrhagic maculae on the trunk and extremities. Among the laboratory findings, WBC was 8, 100 (B 1, St 6, S 77, L 14, Mon 2), RBC 375 x 10(4), Hb 12.5, Ht 37, PLT 3.5 x 10(4), PT 15.6, PTT 68, Fib 158, FDP 10 and AT-III 75. In contrast enhanced CT, an empty triangular sign was observed. On the third hospital day, the patient died of a cerebral hernia. On autopsy, thrombosis was found in the bilateral sigmoid sinus. In the cerebral tissue, congestion was throughout the brain, and many leukemic cells were seen in the dilated blood vessels, but there was no infiltration into the parenchyma. The bone marrow, hypercellular, showed many intermediate type and blastic myeloid cells. The main neurological complications of leukemia are leukemic infiltration and intracranial hemorrhages. Capillary obstructions associated with the disseminated intravascular coagulation (DIC) syndrome are rarely experienced, but obstructions of thick arteries or thick veins such as venous sinuses are seldom seen in general, and most reports of such cases were those resulting from chemotherapy after making a diagnosis of acute leukemia. In the literature, there have been only two reports in our literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherosclerotic Renovascular Disease.

The patient, a 78-year-old Asian male, was brought to the hospital because of acute shortness of breath that had progressively worsened over the course of the day. He complained of a nonproductive cough and claudication after walking 1 block. His past medical history was significant for mild renal insufficiency (serum creatinine 1.5--2.0 mg/dl), the etiology of which was never explored. Although there was a recent history of mild to moderate hypertension, at presentation his blood pressure was noted to be 240/118 mm Hg in both arms. His physical exam at the time of admission was remarkable for grade II hypertensive retinopathy, an S4 gallop, periumbilical systolic bruits, audible femoral arterial bruits and absent distal lower extremity pulses. Initial complete blood count, serum electrolytes and cardiac enzymes (including lactate dehydrogenase) were normal. His blood urea nitrogen and serum creatinine concentrations were 51 and 3.6 mg/dl, respectively, and his urinalysis showed 1+ protein (both by dipstick and sulfasalicylic acid) with a "benign" sediment (0--1 WBC/HPE, 1--2 RBCs/HPF) with occasional granular casts. His electrocardiogram, apart from demonstrating left ventricular hypertrophy with secondary ST-T wave abnormalities, showed no acute changes; his chest X-ray demonstrated cardiomegaly and pulmonary vascular congestion. He was intubated and subsequently treated with increasing parenteral doses of furosemide (40--240 mg) and a nitroglycerine drip (up to 15 mcg/min). Over the course of the first 48 h, his blood pressure was gradually lowered to 170/100 mm Hg. His urine output increased from 20 ml/h to 125/ml/h, and his respiratory status improved, allowing him to be extubated. In spite of adequate control of his blood pressure in the ensuing days (150--170/80--90 mm Hg), his renal function continued to deteriorate. Renal sonography (without Doppler) demonstrated a right kidney of 9.6 cm and a left kidney of 9.3 cm in length without evidence of hydronephrosis. Both kidneys were noted to be echogenic. Assays for antinuclear antibodies and antineutrophilic cytoplasmic antibodies were negative, and the patient's serum complement levels were normal. For several days after his admission, his serum creatinine gradually rose to 10.7 mg/dl, and hemodialysis was initiated for uremic encephalopathy. Because of the high index of suspicion for renal artery stenosis as the case of both his hypertension and renal failure, a renal angiogram was performed. It revealed a 90% occlusion of the right renal artery with ostial involvement and a 70% occlusion of the left renal artery; both kidneys had poor distal renal vasculature and there was marked atherosclerotic disease of the aorta. After being hemodialyzed for 3 treatments, his renal function began to improve spontaneously. His serum creatinine returned to 3.4 mg/dl, and a subsequent 24-hour urine demonstrated a creatinine clearance of 20 ml/min and an excretion of 1.2 g of protein. Following his discharge from the hospital, his renal function remained unchanged for 3 years, and his blood pressure was easily controlled on monotherapy with a long-acting calcium channel blocker. He recently died from pneumonia.

[Occurrence of disseminated intravascular coagulation in purulent meningitis and influence on mortality in 118 patients].

Disseminated intravascular coagulation (DIC) is an important, but not satisfactory explained risk factor of death in purulent meningitis (PM). Evaluation of: 1) acute thrombocytopenia (ATP) in patients with PM, 2) dynamics in changes of peripheral blood platelet (PLT) count and serum coagulation factors, 3) correlation between acute DIC and mortality in PM. Analysis ofATP (platelets < or = 150 K/microL and/or decrease in PLT > or = 100 K/microL/24 hours) and prothrombin ratio, fibrinogen, d-dimmer and antithrombin III in survivors and nonsurvivors in 118 adult patients with PM. 37 further patients have been disclosed because of non-bacterial PM or chronic conditions predisposing to ATP or DIC. DIC defined as ATP occurred in 56 %, defined as elevated d-dimmer level in 72%. 16 (14%) patients died. Mortality correlated significantly with the lowest PLT count on first 3. days (p=0,049) and with PLT decline (p=0,015). Differences in survivors/nonsurvivors were observed in: ATP on 1. day 48% vs. 75% (p<0,05), daily PLT decline 9%/day vs. 32%/day (p<0,05), prothrombin ratio 89% vs. 74% (p<0,05) and INR 1,2 vs. 1,7 (p<0,005). DIC is an important risk factor in PM. Aggravated DIC do correlate significantly with higher risk of death.