Controversial question, since amiodarone (the dose is correct, 300mg), is administered after the third shock, and not after the first defibrillation, which is what we are told in the statement. Although, be careful, that is what the guidelines say. I am sure that more than one of us has administered amiodarone as soon as we have had venous access available in the event of a shockable rhythm. The other options are incorrect.

Controversial question, since amiodarone (the dose is correct, 300mg), is administered after the third shock, and not after the first defibrillation, which is what we are told in the statement. Although, be careful, that is what the guidelines say. I am sure that more than one of us has administered amiodarone as soon as we have had venous access available in the event of a shockable rhythm. [HIDDEN]

A 22-year-old woman presents with sudden cardiac arrest with a rhythm that is considered amenable to defibrillation. Chest compressions and ventilations are being performed, a defibrillator shock has been delivered, and a peripheral venous line has been cannulated. Which of the following would be correct next:

Administration of 150 mg of intravenous amiodarone.

Administration of 300 mg of intravenous amiodarone.

Administration of 1 mg of intravenous atropine.

Administer 2 mg of intravenous atropine.

Pediatric advanced life support

Defibrillations/shocks first shock should be 2 J/kg second shock should be 4 J/kg all other shocks should be ≥ 4 J/kg with max of 10 J/kg Medicines that can be given during treatment of cardiac arrest are listed below. The doses listed below are for IV/IO medicationa. Medications via endotracheal tube (ET) are often given at higher doses. epinephrine: 0.01 mg/kg every 3–5 minutes with max single dose of 1 mg amiodarone: 5 mg/kg initially, can repeat 2 more times (total of 3 doses), max of 300 mg per dose, max 15 mg/kg, given for refractory VF and pVT lidocaine: 1 mg/kg initially with continuous infusion of 20-50 mcg/kg/min after, given for refractory VF and pVT magnesium sulfate: 25–50 mg/kg diluted in 10 ml D5W (5% dextrose) and infused over 1–2 minutes, max 2g per dose, given for pulseless torsades de pointes (a type of ventricular tachycardia)

[The new 2005 resuscitation guidelines of the European Resuscitation Council: comments and supplements].

The new CPR guidelines are based on a scientific consensus which was reached by 281 international experts. Chest compressions (100/min, 4-5 cm deep) should be performed in a ratio of 30:2 with ventilation (tidal volume 500 ml, Ti 1 s, FIO2 if possible 1.0). After a single defibrillation attempt (initially biphasic 150-200 J, monophasic 360 J, subsequently with the respective highest energy), chest compressions are initiated again immediately for 2 min. Endotracheal intubation is the gold standard; other airway devices may be employed as well depending on individual skills. Drug administration routes for adults and children: first choice IV, second choice intraosseous, third choice endobronchial [epinephrine dose 2-3x (adults) or 10x (pediatric patients) higher than IV]. Vasopressors: 1 mg epinephrine every 3-5 min IV. After the third unsuccessful defibrillation attempt amiodarone IV (300 mg); repetition (150 mg) possible. Sodium bicarbonate (1 ml/kg 8.4%) only in excessive hyperkalemia, metabolic acidosis, or intoxication with tricyclic antidepressants. Consider atropine (3 mg) and aminophylline (5 mg/kg). Thrombolysis during spontaneous circulation only in myocardial infarction or massive pulmonary embolism; during CPR only during massive pulmonary embolism. Cardiopulmonary bypass only after cardiac surgery, hypothermia or intoxication. Pediatrics: best improvement in outcome by preventing cardiocirculatory collapse. Alternate chest thumps and chest compression (infants), or abdominal compressions (>1-year-old) in foreign body airway obstruction. Initially five breaths, followed by chest compressions (100/min; approximately 1/3 of chest diameter): ventilation ratio 15:2. Treatment of potentially reversible causes (4 "Hs", "HITS": hypoxia, hypovolemia, hypo- and hyperkaliemia, hypothermia, cardiac tamponade, intoxication, thrombo-embolism, tension pneumothorax). Epinephrine 10 microg/kg IV or intraosseously, or 100 microg (endobronchially) every 3-5 min. Defibrillation (4 J/kg; monophasic oder biphasic) followed by 2 min CPR, then ECG and pulse check. Newborns: inflate the lungs with bag-valve mask ventilation. If heart rate<60/min chest compressions:ventilation ratio 3:1 (120 chest compressions/min). Postresuscitation phase: initiate mild hypothermia [32-34 degrees C for 12-24 h; slow rewarming (<0.5 degrees C/h)]. Prediction of CPR outcome is not possible at the scene; determining neurological outcome within 72 h after cardiac arrest with evoked potentials, biochemical tests and physical examination. Even during low suspicion for an acute coronary syndrome, record a prehospital 12-lead ECG. In parallel to pain therapy, aspirin (160-325 mg PO or IV) and in addition clopidogrel (300 mg PO). As antithrombin, heparin (60 IU/kg, max. 4000 IU) or enoxaparine. In ST-segment elevation myocardial infarction, define reperfusion strategy depending on duration of symptoms until PCI (prevent delay>90 min until PCI). Stroke is an emergency and needs to be treated in a stroke unit. A CT scan is the most important evaluation, MRT may replace a CT scan. After hemorrhage exclusion, thrombolysis within 3 h of symptom onset (0.9 mg/kg rt-PA IV; max 90 mg within 60 min, 10% of the entire dosage as initial bolus, no aspirin, no heparin within the first 24 h). In severe hemorrhagic shock, definite control of bleeding is the most important goal. For successful CPR of trauma patients, a minimal intravascular volume status and management of hypoxia are essential. Aggressive fluid resuscitation, hyperventilation, and excessive ventilation pressure may impair outcome in severe hemorrhagic shock. Despite bad prognosis, CPR in trauma patients may be successful in select cases. Any CPR training is better than nothing; simplification of contents and processes remains important.

Anaphylactic Shock as a Rare Side Effect of Intravenous Amiodarone.

Amiodarone is a very commonly used antiarrhythmic agent. However, it has a wide variety of systemic side effects as well as many hypersensitivity and allergic reactions, ranging from angioedema to anaphylactic shock in patients who have iodine allergies. We present a rare and unique case of an 86-year-old female who developed anaphylactic shock from intravenous (IV) amiodarone. She had no reported allergies to iodine or iodinated contrast. She had a history of chronic persistent atrial fibrillation and was being maintained on oral amiodarone as an outpatient. She was admitted with shortness of breath and was found to have atrial fibrillation with rapid ventricular response. She was started on an IV amiodarone bolus. Immediately after a few milliliters of infusion, she complained of shortness of breath, with facial flushing and generalized blanching erythema, followed by severe hypotension and cardiopulmonary arrest. IV amiodarone infusion was suspected to be the culprit and was discontinued immediately. IV epinephrine 0.3 mg was administered, followed by the advanced cardiovascular life support (ACLS) protocol for cardiopulmonary arrest. She did not respond to the standard ACLS protocol and continued to remain in cardiopulmonary arrest. A spot diagnosis of anaphylactic reaction to IV amiodarone was made, and she was started on IV epinephrine infusion 0.1 µg/kg/minute, and immediate return of spontaneous circulation was achieved. She was started on IV methylprednisolone 125 mg, IV famotidine 20 mg, and IV diphenhydramine 25 mg. She was intubated and required mechanical ventilation. She was successfully extubated later and safely discharged, receiving oral metoprolol 25 mg for rate control and PO rivaroxaban 20 mg once daily. Anaphylactic shock from IV amiodarone administration is a potentially fatal complication observed in patients with prior reported allergies to iodine or iodinated contrast media. It has rarely been reported in the absence of prior allergy to iodine or iodinated contrast media. Prompt recognition by clinicians is prudent for early diagnosis and appropriate treatment.

[Comments on the 2010 guidelines on cardiopulmonary resuscitation of the European Resuscitation Council].

Administer chest compressions (minimum 100/min, minimum 5 cm depth) at a ratio of 30:2 with ventilation (tidal volume 500-600 ml, inspiration time 1 s, F(I)O₂ if possible 1.0). Avoid any interruptions in chest compressions. After every single defibrillation attempt (initially biphasic 120-200 J, monophasic 360 J, subsequently with the respective highest energy), chest compressions are initiated again immediately for 2 min independent of the ECG rhythm. Tracheal intubation is the optimal method for securing the airway during resuscitation but should be performed only by experienced airway management providers. Laryngoscopy is performed during ongoing chest compressions; interruption of chest compressions for a maximum of 10 s to pass the tube through the vocal cords. Supraglottic airway devices are alternatives to tracheal intubation. Drug administration routes for adults and children: first choice i.v., second choice intraosseous (i.o.). Vasopressors: 1 mg epinephrine every 3-5 min i.v. After the third unsuccessful defibrillation amiodarone (300 mg i.v.), repetition (150 mg) possible. Sodium bicarbonate (50 ml 8.4%) only for excessive hyperkaliemia, metabolic acidosis, or intoxication with tricyclic antidepressants. Consider aminophylline (5 mg/kgBW). Thrombolysis during spontaneous circulation only for myocardial infarction or massive pulmonary embolism; during on-going cardiopulmonary resuscitation (CPR) only when indications of massive pulmonary embolism. Active compression-decompression (ACD-CPR) and inspiratory threshold valve (ITV-CPR) are not superior to good standard CPR. Most effective improvement of outcome by prevention of full cardiorespiratory arrest. Basic life support: initially five rescue breaths, followed by chest compressions (100-120/min depth about one third of chest diameter), compression-ventilation ratio 15:2. Foreign body airway obstruction with insufficient cough: alternate back blows and chest compressions (infants), or abdominal compressions (children >1 year). Treatment of potentially reversible causes: ("4 Hs and 4 Ts") hypoxia and hypovolaemia, hypokalaemia and hyperkalaemia, hypothermia, and tension pneumothorax, tamponade, toxic/therapeutic disturbances, thrombosis (coronary/pulmonary). Advanced life support: adrenaline (epinephrine) 10 µg/kgBW i.v. or i.o. every 3-5 min. Defibrillation (4 J/kgBW; monophasic or biphasic) followed by 2 min CPR, then ECG and pulse check. NEWBORNS: Initially inflate the lungs with bag-valve mask ventilation (p(AW) 20-40 cmH₂O). If heart rate remains <60/min, start chest compressions (120 chest compressions/min) and ventilation with a ratio 3:1. Maintain normothermia in preterm babies by covering them with foodgrade plastic wrap or similar. POSTRESUSCITATION PHASE: Early protocol-based intensive care stabilization; initiate mild hypothermia early regardless of initial cardiac rhythm [32-34°C for 12-24 h (adults) or 24 h (children); slow rewarming (<0.5°C/h)]. Consider percutaneous coronary intervention (PCI) in patients with presumed cardiac ischemia. Prediction of CPR outcome is not possible at the scene, determine neurological outcome <72 h after cardiac arrest with somatosensory evoked potentials, biochemical tests and neurological examination. ACUTE CORONARY SYNDROME: Even if only a weak suspicion of an acute coronary syndrome is present, record a prehospital 12-lead ECG. In parallel to pain therapy, administer aspirin (160-325 mg p.o. or i.v.) and clopidogrel (75-600 mg depending on strategy); in ST-elevation myocardial infarction (STEMI) and planned PCI also prasugrel (60 mg p.o.). Antithrombins, such as heparin (60 IU/kgBW, max. 4000 IU), enoxaparin, bivalirudin or fondaparinux depending on the diagnosis (STEMI or non-STEMI-ACS) and the planned therapeutic strategy. In STEMI define reperfusion strategy depending on duration of symptoms until PCI, age and location of infarction. TRAUMA: In severe hemorrhagic shock, definitive control of bleeding is the most important goal. For successful CPR of trauma patients a minimal intravascular volume status and management of hypoxia are essential. Aggressive fluid resuscitation, hyperventilation and excessive ventilation pressure may impair outcome in patients with severe hemorrhagic shock. Any CPR training is better than nothing; simplification of contents and processes is the main aim.

Advanced life support

Algorithms ALS assumes that basic life support (bag-mask administration of oxygen and chest compressions) are administered. The main algorithm of ALS, which is invoked when actual cardiac arrest has been established, relies on the monitoring of the electrical activity of the heart on a cardiac monitor. Depending on the type of cardiac arrhythmia, defibrillation is applied, and medication is administered. Oxygen is administered and endotracheal intubation may be attempted to secure the airway. At regular intervals, the effect of the treatment on the heart rhythm, as well as the presence of cardiac output, is assessed. Medication that may be administered may include adrenaline (epinephrine), amiodarone, atropine, bicarbonate, calcium, potassium and magnesium. Saline or colloids may be administered to increase the circulating volume.

Asystole

Asystole is treated by cardiopulmonary resuscitation (CPR) combined with an intravenous vasopressor such as epinephrine (a.k.a. adrenaline). Sometimes an underlying reversible cause can be detected and treated (the so-called "Hs and Ts", an example of which is hypokalaemia). Several interventions previously recommended—such as defibrillation (known to be ineffective on asystole, but previously performed in case the rhythm was actually very fine ventricular fibrillation) and intravenous atropine—are no longer part of the routine protocols recommended by most major international bodies. Asystole may be treated with 1 mg epinephrine by IV every 3–5 minutes as needed.

Arrhythmias in the intensive care patient.

Atrial fibrillation, atrial flutter, AV-nodal reentry tachycardia with rapid ventricular response, atrial ectopic tachycardia, and preexcitation syndromes combined with atrial fibrillation or ventricular tachyarrhythmias are typical arrhythmias in intensive care patients. Most frequently, the diagnosis of the underlying arrhythmia is possible from the physical examination, the response to maneuvers or drugs, and the 12-lead surface electrocardiogram. In all patients with unstable hemodynamics, immediate DC-cardioversion is indicated. Conversion of atrial fibrillation to sinus rhythm is possible using antiarrhythmic drugs. Amiodarone has a conversion rate in atrial fibrillation of up to 80%. However, caution in the use of short-term administration of intravenous amiodarone in critically ill patients with recent-onset atrial fibrillation is absolutely necessary, and the duration of therapy should not exceed 24 to 48 hours. Ibutilide represents a relatively new class III antiarrhythmic agent that has been reported to have conversion rates of 50% to 70%; it seems that ibutilide is even successful when intravenous amiodarone failed to convert atrial fibrillation. Newer studies compared the outcome of patients with atrial fibrillation and rhythm- or rate-control. Data from these studies (AFFIRM, RACE) clearly showed that rhythm control is not superior to rate control for the prevention of death and morbidity from cardiovascular causes. Therefore, rate-control may be an appropriate therapy in patients with recurrent atrial fibrillation after DC-cardioversion. Acute therapy of atrial flutter in intensive care patients depends on the clinical presentation. Atrial flutter can most often be successfully cardioverted to sinus rhythm with energies less than 50 joules. Ibutilide trials showed efficacy rates of 38-76% for conversion of atrial flutter to sinus rhythm compared with conversion rates of 5-13% when intravenous flecainide, propafenone, or verapamil was administered. In addition, a high dose (2 mg) of ibutilide was more effective than sotalol (1.5 mg/kg) in conversion of atrial flutter to sinus rhythm (70% versus 19%). There is general agreement that bystander first aid, defibrillation, and advanced life support is essential for neurologic outcome in patients after cardiac arrest due to ventricular tachyarrhythmias. The best survival rate from cardiac arrest can be achieved only when (1) recognition of early warning signs, (2) activation of the emergency medical services system, (3) basic cardiopulmonary resuscitation, (4) defibrillation, (5) management of the airway and ventilation, and (6) intravenous administration of medications occurs as rapidly as possible. Public access defibrillation, which places automatic external defibrillators in the hands of trained laypersons, seems to be an ideal approach in the treatment of ventricular fibrillation. The use of automatic external defibrillators by basic life support ambulance providers or first responder in early defibrillation programs has been associated with a significant increase in survival rates. Drugs such as lidocaine, procainamide, sotalol, amiodarone, or magnesium were recommended for treatment of ventricular tachyarrhythmias in intensive care patients. Amiodarone is a highly efficacious antiarrhythmic agent for many cardiac arrhythmias, ranging from atrial fibrillation to malignant ventricular tachyarrhythmias, and seems to be superior to other antiarrhythmic agents.

Defibrillation -- Technique or Treatment

According to the ACLS VF/pulseless VT algorithm outlined by AHA 1 mg of epinephrine should be administered intravenously every 3 to 5 minutes during the resuscitation after the first unsuccessful defibrillation. High-quality CPR is immediately resumed after the second shock for 2 minutes. If VF or pulseless VT persists at the next pulse and rhythm check, the ACLS algorithm allows for 300 mg of amiodarone to be administered as a bolus intravenously during the resuscitation. If additional doses of antiarrhythmic drugs are needed, 150 mg of amiodarone may be given or 1 mg/kg to 1.5 mg/kg of lidocaine may be administered. According to the current AHA guidelines, epinephrine and amiodarone are preferred over lidocaine. [6]

Atropine

Heart Injections of atropine are used in the treatment of symptomatic or unstable bradycardia. Atropine was previously included in international resuscitation guidelines for use in cardiac arrest associated with asystole and PEA, but was removed from these guidelines in 2010 due to a lack of evidence for its effectiveness. For symptomatic bradycardia, the usual dosage is 0.5 to 1 mg IV push, may repeat every 3 to 5 minutes up to a total dose of 3 mg (maximum 0.04 mg/kg). Atropine is also useful in treating second-degree heart block Mobitz type 1 (Wenckebach block), and also third-degree heart block with a high Purkinje or AV-nodal escape rhythm. It is usually not effective in second-degree heart block Mobitz type 2, and in third-degree heart block with a low Purkinje or ventricular escape rhythm. Atropine has also been used in an effort to prevent a low heart rate during intubation of children; however, evidence does not support this use.

Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. Prospective, randomized, between subjects, experimental design. Laboratory. Male Yorkshire-cross swine (N = 35), seven per group. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. Rate of ROSC, time to ROSC, and odds of ROSC. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

[Pediatric advanced life support].

Advanced life support (ALS) includes all the procedures and maneuvers used to restore spontaneous circulation and breathing, thus minimizing brain injury. The fundamental steps of ALS are airway control with adjuncts, ventilation with 100% oxygen, vascular access and fluid and drug administration, and monitoring to diagnose and treat arrhythmias. Airway control can be achieved by means of oropharyngeal airway, endotracheal intubation, and alternative methods (laryngeal mask and cricothyroidotomy). Vascular access can be achieved by the peripheral venous, intraosseous, central venous, and tracheal routes. The most frequent rhythms found in children with cardiorespiratory arrest are nonshockable (asystole, severe bradycardia, pulseless electrical activity, and complete atrioventricular block). In these cases, adrenaline continues to be the essential drug. Currently, low adrenaline doses (0.01 mg/kg IV and 0.1 mg/kg intratracheal administration) are recommended throughout the resuscitation period. Amiodarone (5 mg/kg) is the drug of choice in cases of ventricular fibrillation refractory to electric shock. The treatment sequence for shockable rhythms (ventricular fibrillation and pulseless ventricular tachycardia) is one 4 J/kg electric shock, followed by cardiopulmonary resuscitation (chest compressions and ventilation) for 2 minutes with subsequent reassessment of the electrocardiographic rhythm. Adrenaline must be administered immediately before the third electric shock and subsequently every 3-5 minutes. Amiodarone must be administered immediately before the fourth shock.

Pulseless electrical activity

A priority in resuscitation is placement of an intravenous or intraosseous line for administration of medications. The mainstay of drug therapy for PEA is epinephrine (adrenaline) 1 mg every 3–5 minutes. Although previously the use of atropine was recommended in the treatment of PEA/asystole, this recommendation was withdrawn in 2010 by the American Heart Association due to lack of evidence for therapeutic benefit. Epinephrine too has a limited evidence base, and it is recommended on the basis of its mechanism of action. Sodium bicarbonate 1meq per kilogram may be considered in this rhythm as well, although there is little evidence to support this practice. Its routine use is not recommended for patients in this context, except in special situations (e.g. preexisting metabolic acidosis, hyperkalemia, tricyclic antidepressant overdose).

Cardiac arrest after intravenous metoclopramide - a case of five repeated injections of metoclopramide causing five episodes of cardiac arrest.

We describe a patient where intravenous injection of metoclopramide was immediately followed by asystole repeatedly. The patient received metoclopramide 10 mg i.v. five times during 48 h. After interviewing the attending nurses and reviewing the written documentation, it is clear that every administration of metoclopramide was immediately (within s) followed by asystole. The asystole lasted 15-30 s on four occasions, on one occasion it lasted 2 min. The patient received atropine 0.5-1 mg and chest compressions, before sinus rhythm again took over. We interpret this as episodes of cardiac arrest caused by metoclopramide. The rapid injection via the central venous route and the concomitant tapering of dopamine infusion might have contributed in precipitating the adverse drug reaction.

Current and investigational therapies for the treatment of refractory ventricular fibrillation.

Esmolol, dual sequential defibrillation, vector change defibrillation, and left stellate ganglion block are presented and reviewed for the treatment of refractory ventricular fibrillation. Although no formal definition has been established for refractory ventricular fibrillation, the literature describes it as a pulseless ventricular arrhythmia that persists despite 3 standard defibrillation attempts, administration of amiodarone 300 mg intravenously, and provision of three 1-mg intravenous doses of epinephrine. Evolving literature surrounding resuscitation in this particular subset of cardiac arrest challenges the efficacy of traditional therapies, such as epinephrine, and suggests that other treatment modalities may improve outcomes. Case reports, case series, and small retrospective studies have pointed to benefit when utilizing a variety of therapies, namely, esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block, in patients with refractory ventricular fibrillation arrest. A mounting, although limited, body of evidence suggests that esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block may be effective at terminating refractory ventricular fibrillation and improving patient outcomes. Further evidence is required before these therapies can be adopted as standard practice; however, as key members of the code response team, it is imperative for pharmacists to be familiar with the supporting evidence, safety considerations, and logistical challenges of utilizing these treatments during arrest.

InternalMed_Harrison

500–800 mg, followed by continuous infusion at 2–5 mg/min) is now rarely used in this setting but may be tried for persisting, hemodynamically stable arrhythmias. Intravenous calcium gluconate is no longer considered safe or necessary for routine administration. It is used only in patients in whom acute hyperkalemia is known to be the triggering event for resistant VF, in the presence of known hypocalcemia, or in patients who have received toxic doses of calcium channel antagonists. Cardiac arrest due to bradyarrhythmias or asystole (B/A cardiac arrest) is managed differently (Fig. 327-3B). The patient is promptly intubated, CPR is continued, and an attempt is made to control hypoxemia and acidosis and identify other reversible causes. Epinephrine may be given intravenously or by an intraosseous route. Atropine is no longer considered effective for asystole or PEA, but can be used for bradyarrhythmias. External pacing devices are used to attempt to establish a regular rhythm when

[Drug therapy in cardiopulmonary resuscitation].

In the year 2000, new international guidelines for cardiopulmonary resuscitation (CPR) were published by the American Heart Association, and the European Resuscitation Council. These guidelines are evidence-based, indicating that these recommendations are based primarily on interpretation of data from clinical studies. Levels of recommendation range from class I (proven safe and useful), class IIa (intervention of choice), IIb (alternative intervention), indeterminate (research stage), and class III (unacceptable, no benefit). Administration of drugs during CPR should be performed intravenously or intraosseously (class IIa) or, as a second-line approach, endotracheally (class IIb). Due to lack of evidence, the standard dose of 1 mg epinephrine to treat ventricular fibrillation, pulseless electrical activity, or asystole was categorized as class indeterminate; while a single dose of 40 units vasopressin to treat adults with shock-refractory ventricular fibrillation received a IIb recommendation. Owing to a lack of clinical data, the use of vasopressin was neither recommended to treat adults with pulseless electrical activity or asystole, nor for the use in children. Both endothelin and calcium were not recommended for routine use (class indeterminate). Careful titration of acid-base status with 1 mL/kg 8.4% sodium bicarbonate should only be administered if indicated by blood gas analysis (class indeterminate). If 1 mg epinephrine fails to be effective in adult patients with pulseless electrical activity or asystole, 1 mg atropine can be administered (class indeterminate). Regarding antiarrhythmic drugs, 300 mg amiodarone (class IIb) showed the best results in shock-refractory ventricular fibrillation. The postresuscitation phase has the goal to achieve the best possible neurological performance after return of spontaneous circulation, which requires careful optimization of organ functions.

Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation.

Whether antiarrhythmic drugs improve the rate of successful resuscitation after out-of-hospital cardiac arrest has not been determined in randomized clinical trials. We conducted a randomized, double-blind, placebo-controlled study of intravenous amiodarone in patients with out-of-hospital cardiac arrest. Patients who had cardiac arrest with ventricular fibrillation (or pulseless ventricular tachycardia) and who had not been resuscitated after receiving three or more precordial shocks were randomly assigned to receive 300 mg of intravenous amiodarone (246 patients) or placebo (258 patients). The treatment groups had similar clinical profiles. There was no significant difference between the amiodarone and placebo groups in the duration of the resuscitation attempt (42+/-16.4 and 43+/-16.3 minutes, respectively), the number of shocks delivered (4+/-3 and 6+/-5), or the proportion of patients who required additional antiarrhythmic drugs after the administration of the study drug (66 percent and 73 percent). More patients in the amiodarone group than in the placebo group had hypotension (59 percent vs. 48 percent, P=0.04) or bradycardia (41 percent vs. 25 percent, P=0.004) after receiving the study drug. Recipients of amiodarone were more likely to survive to be admitted to the hospital (44 percent, vs. 34 percent of the placebo group; P=0.03). The benefit of amiodarone was consistent among all subgroups and at all times of drug administration. The adjusted odds ratio for survival to admission to the hospital in the amiodarone group as compared with the placebo group was 1.6 (95 percent confidence interval, 1.1 to 2.4; P=0.02). The trial did not have sufficient statistical power to detect differences in survival to hospital discharge, which differed only slightly between the two groups. In patients with out-of-hospital cardiac arrest due to refractory ventricular arrhythmias, treatment with amiodarone resulted in a higher rate of survival to hospital admission. Whether this benefit extends to survival to discharge from the hospital merits further investigation.

Cardiac arrest

, medications other than epinephrine (adrenaline), while included in guidelines, have not been shown to improve survival to hospital discharge following out-of-hospital cardiac arrest. This includes the use of atropine, lidocaine, and amiodarone. Epinephrine in adults, as of 2019, appears to improve survival but does not appear to improve neurologically normal survival. It is generally recommended every five minutes. Epinephrine acts on the alpha-1 receptor, which in turn increases the blood flow that supplies the heart. This would assist with providing more oxygen to the heart. Based on 2019 guidelines, 1mg of epinephrine may be administered to patients every 3-5 minutes, but doses higher than 1mg epinephrine are not recommended for routine use in cardiac arrest. If the patient has a non-shockable rhythm, the epinephrine should be administered as soon as possible. For a shockable rhythm, epinephrine should only be administered after initial defibrillation attempts have failed.

Asystole and its treatment: the possible role of the parasympathetic nervous system in cardiac arrest.

Parasympathetic tone may be high during ventricular asystole because of reflex vagal stimulation from a number of sources. Eight patients in cardiac arrest were treated with cardiopulmonary resuscitation. All eight patients had ventricular asystole as the initial rhythm or as the result of defibrillation. Six patients failed to respond to 5 cc to 20 cc of 1:10,000 epinephrine intravenously (IV). In all eight cases a regular rhythm (sinus in seven, idioventricular in one) appeared within 30 seconds of administration of the last dose of atropine (1 mg to 2 mg IV). Five patients (62.5%) lived 12 hours, three (37.5%) were discharged from the hospital. These results suggest that atropine may be of value in the treatment of ventricular asystole.

Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation.

Lidocaine has been the initial antiarrhythmic drug treatment recommended for patients with ventricular fibrillation that is resistant to conversion by defibrillator shocks. We performed a randomized trial comparing intravenous lidocaine with intravenous amiodarone as an adjunct to defibrillation in victims of out-of-hospital cardiac arrest. Patients were enrolled if they had out-of-hospital ventricular fibrillation resistant to three shocks, intravenous epinephrine, and a further shock; or if they had recurrent ventricular fibrillation after initially successful defibrillation. They were randomly assigned in a double-blind manner to receive intravenous amiodarone plus lidocaine placebo or intravenous lidocaine plus amiodarone placebo. The primary end point was the proportion of patients who survived to be admitted to the hospital. In total, 347 patients (mean [+/-SD] age, 67+/-14 years) were enrolled. The mean interval between the time at which paramedics were dispatched to the scene of the cardiac arrest and the time of their arrival was 7+/-3 minutes, and the mean interval from dispatch to drug administration was 25+/-8 minutes. After treatment with amiodarone, 22.8 percent of 180 patients survived to hospital admission, as compared with 12.0 percent of 167 patients treated with lidocaine (P=0.009; odds ratio, 2.17; 95 percent confidence interval, 1.21 to 3.83). Among patients for whom the time from dispatch to the administration of the drug was equal to or less than the median time (24 minutes), 27.7 percent of those given amiodarone and 15.3 percent of those given lidocaine survived to hospital admission (P=0.05). As compared with lidocaine, amiodarone leads to substantially higher rates of survival to hospital admission in patients with shock-resistant out-of-hospital ventricular fibrillation.

History of cardiopulmonary resuscitation

Cardiopulmonary resuscitation, also known by the acronym CPR, is an emergency procedure performed in an effort to manually preserve intact brain function by maintaining adequate perfusion of tissue until further measures are taken to restore spontaneous blood circulation and breathing in a person who is in cardiac arrest. CPR is a fundamental component of first aid that is practiced across the world. It is an effective method of keeping a victim of cardiac arrest alive long enough for definitive treatment to be delivered, usually through defibrillation and administration of intravenous drugs such as epinephrine and amiodarone.

Tachyarrhythmias, bradyarrhythmias and acute coronary syndromes.

The incidence of bradyarrhythmias in patients with acute coronary syndrome (ACS) is 0.3% to 18%. It is caused by sinus node dysfunction (SND), high-degree atrioventricular (AV) block, or bundle branch blocks. SND presents as sinus bradycardia or sinus arrest. First-degree AV block occurs in 4% to 13% of patients with ACS and is caused by rhythm disturbances in the atrium, AV node, bundle of His, or the Tawara system. First- or second-degree AV block is seen very frequently within 24 h of the beginning of ACS; these arrhythmias are frequently transient and usually disappear after 72 h. Third-degree AV blocks are also frequently transient in patients with infero-posterior myocardial infarction (MI) and permanent in anterior MI patients. Left anterior fascicular block occurs in 5% of ACS; left posterior fascicular block is observed less frequently (incidence <0.5%). Complete bundle branch block is present in 10% to 15% of ACS patients; right bundle branch block is more common (2/3) than left bundle branch block (1/3). In patients with bradyarrhythmia, intravenous (IV) atropine (1-3 mg) is helpful in 70% to 80% of ACS patients and will lead to an increased heart rate. The need for pacemaker stimulation (PS) is different in patients with inferior MI (IMI) and anterior MI (AMI). Whereas bradyarrhythmias are frequently transient in patients with IMI and therefore do not need permanent PS, there is usually a need for permanent PS in patients with AMI. In these patients bradyarrhythmias are mainly caused by septal necrosis. In patients with ACS and ventricular arrhythmias (VTA) amiodarone is the drug of choice; this drug is highly effective even in patients with defibrillation-resistant out-of-hospital cardiac arrest. There is general agreement that defibrillation and advanced life support is essential and is the treatment of choice for patients with ventricular flutter/fibrillation. If defibrillation is not available in patients with cardiac arrest due to VTA, cardiopulmonary resuscitation is mandatory.

InternalMed_Harrison

route. Atropine is no longer considered effective for asystole or PEA, but can be used for bradyarrhythmias. External pacing devices are used to attempt to establish a regular rhythm when atropine fails for a bradyarrhythmia, but chronotropic agents given intravenously are now recognized as an equally effective alternative. The success rate may be good when B/A arrest is due to acute inferior wall MI or to correctable airway obstruction or drug-induced respiratory depression or with prompt resuscitation efforts. For acute airway obstruction, prompt removal of foreign bodies by the Heimlich maneuver or, in hospitalized patients, by intubation and suctioning of obstructing secretions in the airway is often successful. The prognosis is generally very poor in other causes of this form of cardiac arrest, such as end-stage cardiac or noncardiac diseases. Treatment of PEA is similar to that for bradyarrhythmias, but its outcome is also dismal.

Ventricular Fibrillation -- Treatment / Management -- Acute Management

Due to the high mortality rate and extreme acuity of the condition, VF patients warrant immediate attention. Healthcare professionals should immediately initiate guideline-directed management as per Advanced Cardiac Life Support (ACLS) protocol. There is a lower likelihood of survival if the healthcare professional deviates from the ACLS guidelines. [9] All patients with cardiac arrest should have an initial assessment while receiving quality CPR. Pulseless VT and VF are both shockable rhythm, and once the staff identifies the rhythm as VF, patients should be shocked immediately with 120 to 200 joules on a biphasic defibrillator or 360 joules using a monophasic. Patients receiving prompt defibrillation have shown improved survival (39.3%) compared to patients in whom defibrillation was delayed by 2 minutes or more (22.2%). [10] Administer epinephrine and amiodarone as per ACLS protocol in patients sustaining VF rhythm regardless of receiving 3 shocks. Amiodarone significantly improves survival to hospital admission without affecting survival to hospital discharge. [11] Identifying and addressing the cause of inciting event is equally important. Professionals should undertake cause-specific measures such as securing the airway, correcting electrolytes, administrating fluids, decompressing pneumothorax, draining tamponade while resuscitating the patient. Once the patient attains return of spontaneous circulation (ROSC), physicians should begin a definitive evaluation for coronary artery disease.

Should amiodarone or lidocaine be given to patients who arrest after cardiac surgery and fail to cardiovert from ventricular fibrillation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the administration of amiodarone or lidocaine in patients with refractory VT/VF after cardiac surgery results in successful cardioversion. Altogether more than 434 papers were found using the reported search, from which 23 articles were used to answer the clinical question. No randomized trials have been found in which amiodarone was studied in patients with refractory VF/VT after cardiac surgery. Recommendations on the use of amiodarone in patients with refractory VF/VT in both European and American 2005 Guidelines on Resuscitation are mainly based on expert consensus and are supported by a few randomized trials in patients with out-of-hospital cardiac arrest. We would therefore recommend that amiodarone is the first line drug that should be used in patients with refractory ventricular arrhythmias after cardiac surgery that persist after three failed attempts at cardioversion. Lidocaine should only be used if amiodarone is not available or if its use is contraindicated. Amiodarone should be administered as an intravenous bolus of 300 mg after the third unsuccessful shock.

Effects of early amiodarone administration during and immediately after cardiopulmonary resuscitation in a swine model.

Aim of this experimental study was to compare haemodynamic effects and outcome with early administration of amiodarone and adrenaline vs. adrenaline alone in pigs with prolonged ventricular fibrillation (VF). After 8 min of untreated VF arrest, bolus doses were administered of adrenaline (0.02 mg/kg) and either amiodarone (5 mg/kg) or saline (n = 8 per group) after randomisation. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration, and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt, and the same dose of adrenaline was given every 4th minute during CPR. Haemodynamic monitoring and mechanical ventilation continued for 6 h after return of spontaneous circulation (ROSC), and the pigs were euthanised at 48 h. Researchers were blinded for drug groups throughout the study. There was no difference in rates of ROSC and 48-h survival with amiodarone vs. saline (5/8 vs. 7/8 and 0/8 vs. 3/8, respectively). Diastolic aortic pressure and coronary perfusion pressure were significantly lower with amiodarone during CPR and 1 min after ROSC (P < 0.05). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone (P < 0.01). The incidence of post-resuscitation tachyarrhythmias tended to be higher in the saline group (P = 0.081). Early administration of amiodarone did not improve ROSC or 48-h survival rates, and was associated with worse haemodynamics in this swine model of cardiac arrest.

Amiodarone

In India, amiodarone is marketed (produced by Cipla Pharmaceutical) under the brand name Tachyra. It is also available in intravenous ampules and vials. The dose of amiodarone administered is tailored to the individual and the dysrhythmia that is being treated. When administered orally, the bioavailability of amiodarone is quite variable. Absorption ranges from 22 to 95%, with better absorption when it is given with food. Administration Amiodarone IV should be administered via a central venous catheter. It has a pH of 4.08. If administered outside of the standard concentration of 900 mg/500mL it should be administered using a 0.22 micron filter to prevent precipitate from reaching the patient. Amiodarone IV is a known vesicant. For infusions of longer than 1 hour, concentrations of 2 mg/mL should not be exceeded unless a central venous catheter is used. References Further reading External links

InternalMed_Harrison

If return of circulation fails If return of circulation fails Continue chest compressions, intubate, IV access Epinephrine, 1 mg IV or vasopressin, 40 units IV; follow with repeat defibrillation at maximum energy within 30–60 seconds as required; repeat epinephrine If return of circulation fails Epinephrine, °Dose NaHCO3, 1 meq/kg (° K+) (no longer for routine use; may be used for persistent acidosis -see text) Antiarrhythmics If return of circulation fails Defibrillate, CPR: Drug – Shock – Drug – Shock a second shock is delivered. Multiple shocks given in sequence are 1769 no longer recommended, in order to minimize interruptions of chest compressions. This sequence is continued until personnel capable of, and equipped for, advanced life support are available, although not much data support the notion that shocks and chest compressions alone will revert VF after three shocks have failed.

Pralidoxime

Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. Atropine, which is choice of drug to antagonise the muscarinic effects of organophosphates, is administered even before pralidoxime during the treatment of organophosphate poisoning. While the efficacy of atropine has been well-established, clinical experience with pralidoxime has led to widespread doubt about its efficacy in treatment of organophosphorus poisoning. Dosage Adults: 30 mg/kg (typically 1–2 g), administered by intravenous therapy over 15–30 minutes, repeated 60 minutes later. It can also be given as a 500 mg/h continuous IV infusion. Children: 20–50 mg/kg followed by a maintenance infusion at 5–10 mg/kg/h. Intravenous infusions can lead to respiratory or cardiac arrest if given too quickly.

[Changes in the management of cardiac arrest].

NEW RECOMMENDATIONS: for cardio-pulmonary resuscitation Methods such as mouth to mouth or the search for a pulse, until now the fundamental preliminaries, have now become second line. Everything must be organised to allow for defibrillation as rapidly as possible. NEW MODALITIES FOR CARDIAC MASSAGE: The frequency of compressions recommended is currently 100 per minute in the adult with a rhythm of compression-ventilation reaching 15/2 before intubation. Concerning the haemodynamic agents for cardiac arrest, the efficacy of high doses of adrenalin is not greater than with conventional doses. Vasopressin is not superior to intravenous adrenalin regarding survival at 24 hrs exepet in case of asystoly. Dopamine at a "renal" dose is no longer used. ANTIARRYTHMICS: Amiodarone is part of the decisional tree in the case of ventricular fibrillation or ventricular tachycardia without a pulse. Semi-automatic defibrillator accessibility should be generalized. INFUSED SOLUTIONS: Sodium bicarbonate does not improve the survival except in particular cases. Physiological serum should be preferred to glucosed serum during reanimation.

Paracetamol poisoning

Intravenous acetylcysteine is given as a continuous infusion over 20 hours for a total dose 300 mg/kg. Recommended administration involves infusion of a 150 mg/kg loading dose over 15 to 60 minutes, followed by a 50 mg/kg infusion over four hours; the last 100 mg/kg are infused over the remaining 16 hours of the protocol. Intravenous acetylcysteine has the advantage of shortening hospital stay, increasing both doctor and patient convenience, and allowing administration of activated charcoal to reduce absorption of both the paracetamol and any co-ingested drugs without concerns about interference with oral acetylcysteine. Intravenous dosing varies with weight, specifically in children. For patients less than 20 kg, the loading dose is 150 mg/kg in 3 mL/kg diluent, administered over 60 minutes; the second dose is 50 mg/kg in 7 mL/kg diluent over 4 hours; and the third and final dose is 100 mg/kg in 14 mL/kg diluent over 16 hours.

[Adult cardio-respiratory arrest: guidelines 2005-2010].

At the end of 2005 the new guidelines for the treatment of cardiac arrest were published. The diagnostic criteria of cardiac arrest were simplified and priority is given to thoracic compressions. The ratio of thoracic compressions to insufflations is 30/2. The frequency of thoracic compression is 100/min. In ventricular tachycardia (VT) without pulse or in ventricle fibrillation (VF), defibrillation is attempted with a single external electric shock per cycle. The reanimation cycles are divided in periods of 2 minutes. The two drugs, used to treat VF and VT without pulse, are amiodarone and adrenaline. Adrenaline is not given before the fourth minute into the reanimation and it is administered before the third electrical external shock. In case of asystole or pulse less electrical activity adrenaline is administered as early as possible. Atropine is used in case of pulse less electrical activity with a ventricular response lower than 60/min. In advanced life support a priority is given to whether or not there are treatable secondary causes (4H, 4T), furthermore controlled hypothermia is installed when systemic circulation is restored and optimal support to all vital functions is given.


in thalassemia the ADE is normal.

With the data we are given, the first thing that comes to mind is that it is an arregenerative anemia, since the bone marrow has not responded with an exaltation of erythropoiesis; in this way we have already eliminated the options that speak of regenerative anemia. The next thing that orients us towards the cause is that it is microcytic and hypochromic, which is characteristic of iron deficiency anemia, since folic deficiency gives rise to megaloblastic anemia and active hemorrhage does not give microcytosis or hypochromia, but normocytosis and normochromia. We are almost inclined to answer 5, central arregenerative anemia due to iron deficiency...but there remains answer 1, "thalassemic trait", which makes us uncomfortable and makes us doubt if we are not going for the apparently easy thing...until we remember that in thalassemia the ADE is normal. Definitely, this girl of childbearing age has iron deficiency anemia, something quite common. Those who have doubts can consult "Hematology. Manual básico razonado" by Jesús San Miguel.

With the data we are given, the first thing that comes to mind is that it is an arregenerative anemia, since the bone marrow has not responded with an exaltation of erythropoiesis; [HIDDEN] The next thing that orients us towards the cause is that it is microcytic and hypochromic, which is characteristic of iron deficiency anemia, since folic deficiency gives rise to megaloblastic anemia and active hemorrhage does not give microcytosis or hypochromia, but normocytosis and normochromia. [HIDDEN] [HIDDEN] "thalassemic trait", which makes us uncomfortable and makes us doubt if we are not going for the apparently easy thing...until we remember that in thalassemia the ADE is normal. Definitely, this girl of childbearing age has iron deficiency anemia, something quite common. Those who have doubts can consult "Hematology. Manual básico razonado" by Jesús San Miguel.

A 35-year-old healthy woman consults for asthenia. The CBC shows microcytic and hypochromic anemia (hemoglobin 7 g/dL, mean corpuscular volume 68 fl, mean corpuscular hemoglobin 24 pg) with an elevated red cell distribution amplitude (ADE 20%), decreased reticulocytes (0.3%, 30000/l absolute), decreased hemoglobin content in reticulocytes (17 pg) and discrete thrombocytosis (500000 platelets). With the CBC data, what would be your diagnostic suspicion even without having the patient's biochemistry?

Central anemia, arregenerative, due to folic acid deficiency.

Peripheral, regenerative, hemolytic anemia.

Peripheral anemia, regenerative, due to acute active hemorrhage.

Central anemia, arregenerative, due to iron deficiency.

Iron-deficiency anemia

Blood tests Anemia is often discovered by routine blood tests. A sufficiently low hemoglobin by definition makes the diagnosis of anemia, and a low hematocrit value is also characteristic of anemia. Further studies will be undertaken to determine the anemia's cause. If the anemia is due to iron deficiency, one of the first abnormal values to be noted on a complete blood count, as the body's iron stores begin to be depleted, will be a high red blood cell distribution width, reflecting an increased variability in the size of red blood cells. A low mean corpuscular volume also appears during the course of body iron depletion. It indicates a high number of abnormally small red blood cells. A low mean corpuscular volume, a low mean corpuscular hemoglobin or mean corpuscular hemoglobin concentration, and the corresponding appearance of red blood cells on visual examination of a peripheral blood smear narrows the problem to a microcytic anemia (literally, a small red blood cell anemia).

Anemia

A blood test will provide counts of white blood cells, red blood cells and platelets. If anemia appears, further tests may determine what type it is, and whether it has a serious cause. although of that, it is possible to refer to the genetic history and physical diagnosis. These tests may include: complete blood count (CBC); a CBC is used to count the number of blood cells in a sample of the blood. For anemia, it will likely to be interested in the levels of the red blood cells contained in blood (hematocrit), hemoglobin, mean corpuscular volume. determine the size and shape of red blood cells; some of red blood cells might also be examined for unusual size, shape and color. serum ferritin; This protein helps store iron in the body, a low levels of ferritin usually indicates a low levels of stored iron. serum vitamin B12; low levels usually develop an anemia, vitamin B12 is needed to make red blood cells, which carry oxygen to all parts of human body.

Microcytic anemia

Microcytic anaemia is any of several types of anaemia characterized by small red blood cells (called microcytes). The normal mean corpuscular volume (abbreviated to MCV on full blood count results, and also known as mean cell volume) is approximately 80–100 fL. When the MCV is <80 fL, the red cells are described as microcytic and when >100 fL, macrocytic (the latter occur in macrocytic anemia). The MCV is the average red blood cell size. In microcytic anaemia, the red blood cells (erythrocytes) contain less hemoglobin and are usually also hypochromic, meaning that the red blood cells appear paler than usual. This can be reflected by a low mean corpuscular hemoglobin concentration (MCHC), a measure representing the amount of hemoglobin per unit volume of fluid inside the cell; normally about 320–360 g/L or 32–36 g/dL. Typically, therefore, anemia of this category is described as "microcytic, hypochromic anaemia".

Mean corpuscular hemoglobin

The MCH decreases when Hb synthesis is reduced, or when RBCs are smaller than normal, such as in cases of iron-deficiency anemia. Conversion to SI-units: 1 pg of hemoglobin = 0.06207 femtomole (fmol). Normal value converted to SI-units: 1.68 – 1.92 fmol/cell. See also Red blood cell indices Mean corpuscular hemoglobin concentration Mean corpuscular volume References External links FP Notebook Medline Blood tests

Simultaneous measurement of reticulocyte and red blood cell indices in healthy subjects and patients with microcytic and macrocytic anemia.

Using the new Bayer H*3 hematology analyzer (Leverkusen, Germany), we have determined red blood cell and reticulocyte indices in 64 healthy subjects, in patients with microcytosis due to iron deficiency (58 patients) and heterozygous beta-thalassemia (40 patients), and in patients with macrocytosis (28 patients). We found in all cases that reticulocytes were larger than mature red cells by 24% to 35%, with a hemoglobin concentration 16% to 25% lower and a similar hemoglobin content. The correlation between red cell and reticulocyte indices was strikingly tight (r = .928 for volume, r = .929 for hemoglobin concentration, r = .972 for hemoglobin content) in all four groups, regardless of red blood cell size. The ratio of reticulocyte to red blood cell mean corpuscolar volume (MCV ratio) was constantly above 1. Inversion of the MCV ratio was observed only in four patients. It was always abrupt and transitory and was associated with erythropoietic changes leading to the production of red blood cells of a different volume (treatment of megaloblastic anemia, functional iron deficiency, bone marrow transplantation). In two cases of marrow transplantation, reticulocyte volume fell during the aplastic phase after conditioning chemotherapy and then rapidly increased up to values higher than before; this production of macroreticulocytes was the earliest sign of engraftment.

Red blood cell indices

Red blood cell indices are blood tests that provide information about the hemoglobin content and size of red blood cells. Abnormal values indicate the presence of anemia and which type of anemia it is. Mean corpuscular volume Mean corpuscular volume (MCV) is the average volume of a red blood cell and is calculated by dividing the hematocrit (Hct) by the concentration of red blood cell count. Normal range: 80–100 fL (femtoliter) Mean corpuscular hemoglobin Mean corpuscular hemoglobin (MCH) is the average amount of hemoglobin (Hb) per red blood cell and is calculated by dividing the hemoglobin by the red blood cell count. Normal range: 27-31 pg/cell Mean corpuscular hemoglobin concentration Mean corpuscular hemoglobin concentration (MCHC) is the average concentration of hemoglobin per unit volume of red blood cells and is calculated by dividing the hemoglobin by the hematocrit. Normal range: 32-36 g/dL Red blood cell distribution width

Anemia

* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause. ** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss. Here is a schematic representation of how to consider anemia with MCV as the starting point: Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow. Microcytic Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:

Megaloblastic anemia

Blood findings The blood film can point towards vitamin deficiency: Decreased red blood cell (RBC) count and hemoglobin levels Increased mean corpuscular volume (MCV, >100 fL) and mean corpuscular hemoglobin (MCH) Normal mean corpuscular hemoglobin concentration (MCHC, 32–36 g/dL) Decreased reticulocyte count due to destruction of fragile and abnormal megaloblastic erythroid precursor. The platelet count may be reduced. Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age. Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs). Macrocytes (larger than normal RBCs) are present. Ovalocytes (oval-shaped RBCs) are present. Howell-Jolly bodies (chromosomal remnant) also present.

Mean corpuscular hemoglobin

The mean corpuscular hemoglobin, or "mean cell hemoglobin" (MCH), is the average mass of hemoglobin (Hb) per red blood cell (RBC) in a sample of blood. It is reported as part of a standard complete blood count. MCH value is diminished in hypochromic anemias. It is calculated by dividing the total mass of hemoglobin by the number of red blood cells in a volume of blood. MCH=(Hb*10)/RBC A normal MCH value in humans is 27 to 31 picograms (pg)/cell. The amount of hemoglobin per RBC depends on hemoglobin synthesis and the size of the RBC. The mass of the red cell is determined by the iron (as part of the hemoglobin molecule), thus MCH in picograms is roughly the mass of one red cell. In iron deficiency anemia the cell mass becomes lighter, thus a MCH below 27 pg is an indication of iron deficiency.

Anemia in pregnancy

The most useful test with which to render a diagnosis of anemia is a low RBC count, however hemoglobin and hematocrit values are most commonly used in making the initial diagnosis of anemia. Testing involved in diagnosing anemia in the pregnant person must be tailored to each individual patient. Suggested tests include: hemoglobin and hematocrit (ratio of red blood cells to the total blood volume), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), erythrocyte count (number of red blood cells in the blood), red cell distribution width (RDW), reticulocyte count, and a peripheral smear to assess red blood cell morphology. If iron deficiency is suspected, additional tests such as: serum iron, total iron-binding capacity (TIBC), transferrin saturation, and plasma or serum ferritin may be warranted. It is important to note that references ranges for these values are often not the same for pregnant women. Additionally, laboratory values for pregnancy often change throughout

The platelet count/mean corpuscular hemoglobin ratio distinguishes combined iron and vitamin B12 deficiency from uncomplicated iron deficiency.

Combined deficiencies of iron and cobalamin are common. The aims of this study were to investigate the significance of the parameters of the complete blood count (CBC) in differentiating microcytic anemia due to pure iron deficiency anemia (IDA) from anemia due to combined deficiencies of vitamin B(12) and iron (IDA-B12). The study was carried out with 122 patients (100 female) who had microcytic red blood cell indices with IDA-B12 and 105 patients (95 female) with IDA. Group IDA-B12 patients had decreased hemoglobin levels, mean corpuscular volumes, mean corpuscular hemoglobin (MCH) levels, and MCH concentrations but had increased platelet counts (PLT). Using these parameters, we developed a PLT/MCH ratio parameter that has high values when IDA is accompanied by cobalamin deficiency. The cutoff value of >12.00, with a 74.6% sensitivity and a 41.9% specificity, appears to be the most convenient value for screening. We advise measuring the levels of cobalamin in patients with IDA associated with a high PLT/MCH ratio.

Inherited microcytic anemias.

Inherited microcytic anemias can be broadly classified into 3 subgroups: (1) defects in globin chains (hemoglobinopathies or thalassemias), (2) defects in heme synthesis, and (3) defects in iron availability or iron acquisition by the erythroid precursors. These conditions are characterized by a decreased availability of hemoglobin (Hb) components (globins, iron, and heme) that in turn causes a reduced Hb content in red cell precursors with subsequent delayed erythroid differentiation. Iron metabolism alterations remain central to the diagnosis of microcytic anemia, and, in general, the iron status has to be evaluated in cases of microcytosis. Besides the very common microcytic anemia due to acquired iron deficiency, a range of hereditary abnormalities that result in actual or functional iron deficiency are now being recognized. Atransferrinemia, DMT1 deficiency, ferroportin disease, and iron-refractory iron deficiency anemia are hereditary disorders due to iron metabolism abnormalities, some of which are associated with iron overload. Because causes of microcytosis other than iron deficiency should be considered, it is important to evaluate several other red blood cell and iron parameters in patients with a reduced mean corpuscular volume (MCV), including mean corpuscular hemoglobin, red blood cell distribution width, reticulocyte hemoglobin content, serum iron and serum ferritin levels, total iron-binding capacity, transferrin saturation, hemoglobin electrophoresis, and sometimes reticulocyte count. From the epidemiological perspective, hemoglobinopathies/thalassemias are the most common forms of hereditary microcytic anemia, ranging from inconsequential changes in MCV to severe anemia syndromes.

Normocytic anemia

Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old. Its prevalence increases with age, reaching 44 percent in men older than 85 years. The most common type of normocytic anemia is anemia of chronic disease. Classification A normocytic anemia is when the red blood cells are of normal size. Normocytic anemia is defined when the mean corpuscular volume (MCV) is between 80 and 100 femtolitres (fL), which is within the normal and expected range. However, the hematocrit and hemoglobin are decreased. In contrast, microcytic anemias are defined as an anemia with a mean corpuscular volume (MCV) less than 80 fL and macrocytic anemias have a mean corpuscular volume over 100 fL.

Mean corpuscular volume

Interpretation The normal reference range is typically 80-100 fL. High In pernicious anemia (macrocytic), MCV can range up to 150 femtolitres. (as are an elevated GGT and an AST/ALT ratio of 2:1). Vitamin B12 and/or folic acid deficiency has also been associated with macrocytic anemia (high MCV numbers). Low The most common causes of microcytic anemia are iron deficiency (due to inadequate dietary intake, gastrointestinal blood loss, or menstrual blood loss), thalassemia, sideroblastic anemia or chronic disease. In iron deficiency anemia (microcytic anemia), it can be as low as 60 to 70 femtolitres. In some cases of thalassemia, the MCV may be low even though the patient is not iron deficient. Worked example

Hypochromic anemia

Hypochromic anemia is a generic term for any type of anemia in which the red blood cells are paler than normal. (Hypo- refers to less, and chromic means colour.) A normal red blood cell has a biconcave disk shape and will have an area of pallor in its center when viewed microscopically. In hypochromic cells, this area of central pallor is increased. This decrease in redness is due to a disproportionate reduction of red cell hemoglobin (the pigment that imparts the red color) in proportion to the volume of the cell. Clinically the color can be evaluated by the mean corpuscular hemoglobin (MCH) or mean corpuscular hemoglobin concentration (MCHC). The MCHC is considered the better parameter of the two as it adjusts for effect the size of the cell has on its amount of hemoglobin. Hypochromia is clinically defined as below the normal MCH reference range of 27–33 picograms/cell in adults or below the normal MCHC reference range of 33–36 g/dL in adults.

Laboratory diagnosis of anemia: are the old and new red cell parameters useful in classification and treatment, how?

Anemia is a global problem affecting the population in both developing and developed countries, and there is a debate on which hemoglobin level limit should be used to define anemia in general population and particularly in the elderly. We present herein a laboratory approach to diagnosing the possible causes of anemia based on traditional and new erythroid parameters. In this article, we provide practical diagnostic algorithms that address to differential diagnosis of anemia. Based on both morphological and kinetic classifications, three patterns were considered: microcytic, normocytic, and macrocytic. Main interest is on the clinical usefulness of old and new parameters such as mean cell volume (MCV), red blood cell distribution width (RDW), hypochromic and microcytic erythrocytes, immature reticulocyte fraction (IRF), and some reticulocyte indices such as reticulocyte hemoglobin content and mean reticulocyte volume. The pathophysiologic basis is reviewed in terms of bone marrow erythropoiesis, evaluated by reticulocyte count (increased or normal/decreased) and IRF. The utility of reticulocyte indices in the diagnosis of iron-deficient erythropoiesis (absolute or functional) and in monitoring of response to treatment in nutritional anemia (iron and cobalamin) was also investigated. For each parameter, the availability, the possible clinical applications, and the limitations were evaluated. A discussion on intraindividual biological variation and its implication on the usefulness of conventional reference intervals and in longitudinal monitoring of the patients was also reported. Red cell parameters and reticulocyte indices play an essential role in differential diagnosis of anemia and in its treatment. More efforts are needed in harmonizing parameters whose results are still too different when produced by different analyzers.

Complete blood count

Microcytic anemia is typically associated with iron deficiency, thalassemia, and anemia of chronic disease, while macrocytic anemia is associated with alcoholism, folate and B12 deficiency, use of some drugs, and some bone marrow diseases. Acute blood loss, hemolytic anemia, bone marrow disorders, and various chronic diseases can result in anemia with a normocytic blood picture. The MCV serves an additional purpose in laboratory quality control. It is relatively stable over time compared to other CBC parameters, so a large change in MCV may indicate that the sample was drawn from the wrong patient.

Evaluation of Reticulocyte Parameters in Iron Deficiency, Vitamin B12 Deficiency and Mixed Anemia.

Reticulocytes are the youngest erythrocytes released from the bone marrow into the blood and they circulate for 1-2 days before becoming mature erythrocytes. In literature, there were studies about reticulocyte parameters that could help in differentiation of iron deficiency anemia (IDA) from vitamin B12 deficiency anemia. However, in those studies there were no data about differentiation of mixed anemia (vitamin B12 deficiency and IDA). The purpose of this study is to explore a response to 'could reticulocyte parameters help in differential diagnosis of mixed anemia?' in 6-12 years old children. The study enrolled 26 patients with IDA, 22 patients with mixed anemia, 32 patients with vitamin B12 deficiency, and 32 age and gender matched healthy controls. Blood for hematological parameters such as complete blood count, reticulocyte count, CHr, MCVr, CHCMr were collected into standard tubes containing EDTA. There is a statistically significant difference of both MCV (mean corpuscular volume)/MCVr (Reticulocyte mean corpuscular volume) ratio and MCVr between IDA and controls; in controls and vitamin B12 deficiency anemia; in controls and mixed anemia; in IDA and vitamin B12 deficiency anemia; in IDA and mixed anemia. Also in terms of both CHr and CHCMr (Corpuscular mean hemoglobin concentration of reticulocyte), there is a statistically significant difference between controls and IDA; controls and mixed anemia; IDA and mixed anemia; IDA and vitamin B12 deficiency anemia. In mixed anemia, MCV could be normal or decreased, and in peripheral blood smear erythrocytes cells could be morphologically normal. For this reason diagnosis of mixed anemia is not easy and needs additional laboratory investigations. Our results suggest that in a differential diagnosis of mixed anemia from vitamin B12 deficiency, IDA, and healthy controls, CHr, CHCMr, and MCVr (together with MCV and individually) could be useful. So, with a simple and cheap laboratory parameter, differentiation of mixed anemia could be done.

Anemia analyzer: algorithm and reflex testing in clinical practice leading to efficiency and cost savings.

Anemia is a common disease affecting about 3.5 million people in the United States. In present day clinical practice, a clinician makes a diagnosis of anemia based on low hemoglobin levels discovered during a complete blood count (CBC) test. If the etiology of the anemia is not readily apparent, the clinician orders additional testing to discover the cause of the anemia. Which tests are ordered, in what order these tests are run, and how the information gathered from the tests is used is based primarily on the individual physician's knowledge and expertise. Using this system to determine the cause of anemia is not only labor and resource intensive but it carries a potential for morbidity and an occasional mortality. Utilizing previously published data, we created an algorithmic approach to analyze the cause of anemia in the majority of cases. The algorithm accepts as input three parameters from a CBC test: (1) mean corpuscular volume, (2) red cell distribution width, and (3) reticulocyte count. With these three parameters, the algorithm generates a probable etiology of the anemia. Additionally, the algorithm will automatically order reflex tests needed to confirm the diagnosis. These reflex tests can be modified depending on the policies of the institution using the algorithm, as different institutions may order different tests based on availability and costs. This is a simple algorithm that could be integrated into the CBC test output. When a low hemoglobin level is found, the algorithm suggests the probable etiology and orders reflex tests if they are desired. Such an approach would not only provide cost efficiency and time savings but would also elevate the level of every clinician ordering a CBC to that of an expert hematologist.

Overview on Ordering and Evaluation of Laboratory Tests -- Diagnostic Tests -- Complete Blood Count (CBC)

Common terms in CBC and their normal values are as follows Red Blood Cell (RBC) Count: The number of RBCs per volume of blood (normal value: 4.2 to 6.9 x 109/mm3 Hemoglobin (Hb): Amount of oxygen-carrying capacity of blood (normal value: 130 to 180 g/L in males, 120 to 160 g/L in females) Hematocrit (Hct): Percentage of whole blood occupied by packed RBCs (normal value: 45% to 62% in males, 37% to 48% in females) Mean Corpuscular Volume (MCV): The measure of RBC size (normal value: 80 to 100 micromillimeter) Mean Corpuscular Hemoglobin (MCH): Amount of oxygen-carrying hemoglobin inside RBCs (normal value: 27 to 32 pg/cell) Mean Corpuscular Hemoglobin Concentration (MCHC): Average concentration of Hb inside RBCs (normal value: 32% to 36%) White Blood Cell (WBC) Count: The number of WBCs per volume of blood (normal value: 4.3 to 11 x 109/mm3) WBC differential:

InternalMed_Harrison

The components of the CBC also help in the classification of anemia. Microcytosis is reflected by a lower than normal MCV (<80), whereas high values (>100) reflect macrocytosis. The MCH and MCHC reflect defects in hemoglobin synthesis (hypochromia). Automated cell counters describe the red cell volume distribution width (RDW). The MCV (representing the peak of the distribution curve) is insensitive to the appearance of small populations of macrocytes or microcytes. An experienced laboratory technician I. Complete blood count (CBC) A. Red blood cell count 1. 2. 3. B. Red blood cell indices 1. 2. 3. 4. C. White blood cell count 1. 2. Nuclear segmentation of neutrophils D. Platelet count E. Cell morphology 1. 2. 3. 4. 5. II. A. B. C. III. A. 1. 2. 3. B. Biopsy 1. 2. Morphology aM/E ratio, ratio of myeloid to erythroid precursors. PART 2 Cardinal Manifestations and Presentation of Diseases

Anemia

A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs. A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a

Anemia

Red blood cell size In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.

[Reticulocyte hemoglobin equivalent as a diagnostic marker for the current iron deficiency : Old wine in new bottles].

The reticulocyte hemoglobin equivalent (RET-He) is presented as a biomarker for the diagnostics and monitoring of iron deficiency. The marker is independent of the acute phase and can be determined within a few minutes by a blood count. Due to the approximately 120-day lifetime of erythrocytes, iron deficiency and changes in the iron status of erythropoiesis can first be recognized at a relatively late stage using classical hematological parameters, such as hemoglobin, mean corpuscular volume, mean cellular hemoglobin content and also with determination of hypochromic erythrocytes (% hypo). The RET-He is a cost-effective parameter for the diagnosis and monitoring of the iron supply for erythropoiesis. Reticulocytes, the precursors of mature erythrocytes, are washed out of the bone marrow into the peripheral blood and normally mature within 2 days to mature erythrocytes. The determination of the reticulocyte number therefore enables a timely statement about erythropoiesis. A measurement of the hemoglobin content of reticulocytes therefore reflects the actual iron metabolism of erythropoiesis and enables assessment of the quality of the cells. Changes in the iron status of erythropoiesis can thus be detected much earlier than by determining only the hemoglobin content of mature erythrocytes, i.e. the mean cellular hemoglobin content. It is recommended that the evaluation of RET-He should be carried out as an inexpensive routine preoperative marker of latent anemia in order to identify patients at risk. In the sense of a perioperative prehabilitation and the enhanced recovery after surgery (ERAS) concept, patients with iron deficiency can be treated proactively at an early stage in order to prevent complications and extended hospital stays.

Automated measurement of red blood cell microcytosis and hypochromia in iron deficiency and beta-thalassemia trait.

Some routine red blood cell (RBC) measurements and indexes (count, mean volume, volume dispersion, and mean hemoglobin [HGB] concentration) can be used to differentiate iron deficiency from heterozygous beta-thalassemia. A number of formulas that incorporate two or more of these measurements have been described to amplify such differences. The H*1 hematology analyzer directly measures volume and HGB concentration of individual RBCs. We have assessed the diagnostic usefulness of conventional and new RBC measurements provided by the H*1 on a learning data set that comprised 119 patients with iron deficiency and 172 patients with beta-thalassemia trait, both untreated and uncomplicated. The most striking finding was the inverse behavior of percentages of microcytes (volume, less than 60 fL) and hypochromic RBCs (HGB concentration, less than 280 g/L) in the two conditions. In 162 of 172 patients with beta-thalassemia trait, the percentage of microcytes (mean, 33.1%; central 95th percentile range, 9.2% to 54.5%) was higher than the percentage of hypochromic RBCs (mean, 13.9%; central 95th percentile range, 1.7% to 24.7%). In 105 of 119 patients with iron deficiency, on the contrary, the percentage of hypochromic cells (mean, 34.6%; central 95th percentile range, 9.7% to 73.1%) was higher than the percentage of microcytes (mean, 12.8%; central 95th percentile range, 1.7% to 29.6%). The ratio between the percentage of microcytes and the percentage of hypochromic cells provided by the H*1 (microcytic-hypochromic ratio) was useful in differentiating the two types of microcytic anemia: with the use of a discriminant value of 0.9, the discriminant efficiency of the microcytic-hypochromic ratio was 92.4% (95% confidence interval, 88.8% to 95.2%), higher than that of the five previously described discriminant formulas and simple RBC measurements. When assessed on a test data set that comprised 149 unselected cases of microcytic anemia, a microcytic-hypochromic ratio lower than 0.9 demonstrated high sensitivity (94.0%), specificity (92.3%), and predictive value (94.0%) for the presence of iron-deficient erythropoiesis in patients with isolated iron deficiency, polycythemia vera treated by phlebotomy, and iron deficiency complicating heterozygous thalassemia. In conclusion, our results showed that iron-deficient erythropoiesis is characterized by the production of RBCs with a severely decreased HGB concentration, while microcytes of beta-thalassemia trait are generally smaller, with a more preserved HGB concentration. Such properties, as assessed by the H*1 hematology analyzer, are very useful in distinguishing these two common types of microcytic anemia.

Complete blood count

A low RDW has no clinical significance, but an elevated RDW represents increased variation in red blood cell size, a condition known as anisocytosis. Anisocytosis is common in nutritional anemias such as iron deficiency anemia and anemia due to vitamin B12 or folate deficiency, while people with thalassemia may have a normal RDW. Based on the CBC results, further steps can be taken to investigate anemia, such as a ferritin test to confirm the presence of iron deficiency, or hemoglobin electrophoresis to diagnose a hemoglobinopathy such as thalassemia or sickle cell disease. White blood cells The white blood cell and platelet counts are markedly increased, and anemia is present. The differential count shows basophilia and the presence of band neutrophils, immature granulocytes and blast cells.

Evaluation of anemia in children.

Anemia is defined as a hemoglobin level of less than the 5th percentile for age. Causes vary by age. Most children with anemia are asymptomatic, and the condition is detected on screening laboratory evaluation. Screening is recommended only for high-risk children. Anemia is classified as microcytic, normocytic, or macrocytic, based on the mean corpuscular volume. Mild microcytic anemia may be treated presumptively with oral iron therapy in children six to 36 months of age who have risk factors for iron deficiency anemia. If the anemia is severe or is unresponsive to iron therapy, the patient should be evaluated for gastrointestinal blood loss. Other tests used in the evaluation of microcytic anemia include serum iron studies, lead levels, and hemoglobin electrophoresis. Normocytic anemia may be caused by chronic disease, hemolysis, or bone marrow disorders. Workup of normocytic anemia is based on bone marrow function as determined by the reticulocyte count. If the reticulocyte count is elevated, the patient should be evaluated for blood loss or hemolysis. A low reticulocyte count suggests aplasia or a bone marrow disorder. Common tests used in the evaluation of macrocytic anemias include vitamin B12 and folate levels, and thyroid function testing. A peripheral smear can provide additional information in patients with anemia of any morphology.

Mean Corpuscular Volume -- Etiology

Microcytic anemia is a type of anemia where the average erythrocyte is smaller than normal and much smaller than a leukocyte. On the complete blood count (CBC), its measure is under 80 fL while normal MCV is between 80 to 100 fL. It is commonly seen in chronic iron-deficient anemia, anemia of chronic disease, sideroblastic anemia, and thalassemias but can also occur in other conditions. Microcytic cells can appear to have a larger area of central pallor, especially in the setting of iron-deficient anemia and anemia of chronic disease.

Microcytosis

Red blood cells can be characterised by their haemoglobin content as well as by their size. The haemoglobin content is referred to as the cell's colour. Therefore, there are both "normochromic microcytotic red cells" and "hypochromic, microcytotic red cells". The normochromic cells have a normal concentration of haemoglobin, and are therefore 'red enough' while the hypochromic cells do not; thus the value of the mean corpuscular hemoglobin concentration.The most common cause of microcytosis is iron deficiency anemia. Every time Hb synthesis being impaired in bone marrow microcytosis can occurs such as iron deficiency and Hb pathy may occur in fact when Hb production was impaired: size of each RBCs is decreased in early stage to save mean corpuscular Hb concentration : ie MCHC: so MCV is decreased as compensating mechanism. Treatment See also Macrocytosis References External links

Mechanical hemolytic anemia

Hemolytic phenomena March haemoglobinuria March hemoglobinuria, occurs when hemoglobin is seen in the urine after repetitive impacts on the body, particularly affecting the feet. The word "march" is in reference to the condition arising in soldiers who have been marching for long periods; the condition was first documented in 1881. Runner’s macrocytosis Runner's macrocytosis is a phenomenon of increased red blood cell size as a compensatory mechanism for increased red blood cell turnover. The impact forces from running can lead to red blood cell hemolysis and accelerate red blood cell production. This can shift the ratio of red blood cells towards younger, larger cells. This shift may be reflected in higher than normal mean corpuscular volume (MCV) values, an indicator of red blood cell size. This is not a pathological condition but may indicate a propensity toward iron deficiency anemia due to high red blood cell turnover. References Acquired hemolytic anemia

Red cell indices and therapeutic trial of iron in diagnostic work-up for anemic Thai females.

Anemia is common among Thai females. Thalassemia and iron deficiency are highly prevalent in the Thai population. A therapeutic trial of iron has been used to differentiate between the two conditions, however, no previous study on its usefulness in a Thai population has been reported. Otherwise healthy persons who had complete blood count (CBC) as routine 'check-up' and found to be anemic (Hb < 12 g/dl) at a preventive medicine clinic were tested for hemoglobin typing, serum ferritin, serum iron, and were given oral iron sulfate (120 mg elemental iron per day for at least 2 months) and a repeat CBC on a follow-up visit. Sixty-six individuals, all females, with pre-treatment hemoglobin (Hb) level of 9.5 +/- 1.7 g/dl (mean +/- SD), had complete data for analysis. Final diagnoses were isolated iron deficiency in 23 (34.8%), iron deficient thalassemia traits in 6 (9.1%) and iron-sufficient thalassemia syndromes in 29 (43.9%) anemic subjects. After a therapeutic trial of iron, Hb rose to 12.8 +/- 1.0 g/dl (n = 16, p = 2 x 10(-8)) among the iron deficient group, but not in thalassemia. The authors have identified that the most useful red cell indices that will discriminate between iron deficiency and thalassemia is a combination of red blood cell counts (RBC) > 4.4 x 10(6)/microl and mean corpuscular volume (MCV) < 69 fl. High RBC (> 4.4 x 10(6)/microl) and very low MCV (< 69 fl) is a sensitive (92.9%) and highly specific (100%) criteria for diagnosis of mild thalassemia diseases (Hemoglobin H (HbH), Hemoglobin H-Constant Spring (HbH-CS), and homozygous Hemoglobin E (HbEE)). Conversely, a low RBC (> 4.4 x 10(6)/microl) and/or low to normal MCV (69-85 fl) is highly sensitive (91.3%) but not specific (60%) for the diagnosis of iron deficiency. The authors conclude that a therapeutic trial of iron is useful as a diagnostic test in anemic females except those with high RBC (> 4.4 x 10(6)/microl) and very low MCV (< 69 fl), a subgroup which most likely has thalassemia and are least likely to benefit from iron treatment.

Iron-deficiency anemia

The blood smear of a person with iron-deficiency anemia shows many hypochromic (pale, relatively colorless) and small red blood cells, and may also show poikilocytosis (variation in shape) and anisocytosis (variation in size). With more severe iron-deficiency anemia, the peripheral blood smear may show hypochromic, pencil-shaped cells and, occasionally, small numbers of nucleated red blood cells. The platelet count may be slightly above the high limit of normal in iron-deficiency anemia (termed a mild thrombocytosis), but severe cases can present with thrombocytopenia (low platelet count).