Mechanical Hemolytic Anemia Research Articles

Thrombotic Microangiopathy with Skin Localization Secondary to Cytarabine-Daunorubicin Association: Report of a Case

The thrombotic microangiopathy is a syndrome characterized by the combination of mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In addition to the idiopathic form, several cases are identified as secondary to pregnancy, infections, disease systems, organ transplants, and cancer. Other forms are secondary to drugs including antimitotics. We report the case of a patient followed for acute myelogenous leukemia. She received induction chemotherapy combining daunorubicin and cytarabine, complicated by thrombotic thrombocytopenic purpura.

ADAMTS13, la protéase spécifique du clivage du facteur von Willebrand

ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats) is the specific von Willebrand factor (VWF)-cleaving protease. ADAMTS13 was partially purified from human plasma in 1996 and its gene was cloned in 2001. In case of vascular injury, multimeric VWF is the mediator of both platelet adhesion to the sub-endothelium and platelet aggregation within the microvessels at high shear rates of blood flow. ADAMTS13 regulates VWF adhesive capacity by reducing the size of VWF multimers. A severe functional deficiency of ADAMTS13 (activity lower than 10%) is associated with most cases of thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy characterized by the spontaneous formation, within the microcirculation, of VWF-rich platelet thrombi responsible for a mechanical hemolytic anemia, a consumption thrombocytopenia and a multivisceral ishemia. TTP is a rare disease (4 cases/10(6)/year) with a life-threatening prognosis in the absence of an appropriate treatment in emergency (plasmatherapy). In 90% of cases, TTP is acquired and related to the development of auto-antibodies to ADAMTS13. In the other cases, TTP is inherited via bi-allelic autosomic recessive mutations of ADAMTS13 gene (Upshaw-Schulman syndrome). A better characterization of ADAMTS13 structure/function combined to clinical trials led in TTP patients is crucial to evaluate the relevance of either a -plasma-purified or a -recombinant ADAMTS13 as a therapeutic agent.

Percussion hemoglobinuria - a novel term for hand trauma-induced mechanical hemolysis: a case report

IntroductionExtracorpuscular hemolysis caused by mechanical trauma has been well described in relation to lower extremity use, such as in soldiers and runners. Terms such as "march hemoglobinuria", "foot strike hemolysis" and "runners hemoglobinuria" have previously been coined and are easily recalled. Newer cases, however, are being identified in individuals vigorously using their upper extremities, such as drum players who use their hands to strike the instrument. Given the increased recognition of upper extremity-related mechanical hemolysis and hemoglobinuria in drummers, and the use of hand drumming worldwide, we would like introduce a novel term for this condition and call it "percussion hemoglobinuria".Case presentationA 24-year-old Caucasian man presented with reddish brown discoloration of his urine after playing the djembe drum. Urine examination after a rigorous practice session revealed blood on the dipstick, and 0 to 2 red blood cells per high power field microscopically. The urine sample was negative for myoglobulin. Other causes of hemolysis and hematuria were excluded and cessation of drum playing resulted in resolution of his symptoms.ConclusionsThe association of mechanical trauma-induced hemoglobinuria and playing hand percussion instruments is increasingly being recognized. We, however, feel that the true prevalence is higher than what has been previously recorded in the literature. By coining the term "percussion hemoglobinuria" we hope to raise the awareness of screening for upper extremity trauma-induced mechanical hemolysis in the evaluation of a patient with hemoglobinuria.

Atypical hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early.

The Role of Endothelial Cell Injury in Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) refers to a clinical and pathologic syndrome in which endothelial injury results in the manifestations of thrombocytopenia, microangiopathic hemolytic anemia, and kidney injury. A host of causes may induce endothelial injury and TMA, including enteric bacterial toxins, deficiency or dysfunction of complement regulatory proteins, deficiency or inhibition of von Willebrand factor-cleaving proteases, and factors that inhibit endothelial cell proliferation and turnover. This has led specialists to concentrate on these specific inciting factors in terms of designing treatment and management. However, a key and less recognized factor is the underlying level of endothelial health. Many persons with hereditary causes may remain disease free for years or may never develop disease. Others with acute inciting events, such as Escherichia coli O157 enteritis, never manifest TMA. Experimental studies document the importance of specific factors, such as endothelial nitric oxide levels, in helping protect animals from TMA. This suggests that one might approach the management of TMA not simply with specific treatments aimed at the underlying hereditary cause or inciting event, but rather at general measures that may improve overall endothelial health. We propose studies to determine whether interventions that improve endothelial health, such as the administration of angiotensin-converting enzyme inhibitors, statins, vitamin C, allopurinol, or nitric oxide-producing drugs, may be able to prevent TMA, even in persons with underlying hereditary conditions that otherwise would predispose them to these diseases.

Thrombotic thrombocytopenic purpura associated with syaphylococcus aureus endocarditis in a diabetic with furunculosis

Thrombotic thrombocytopenic purpura (TTP) is an uncommon and potentially fatal syndrome which is due to either congenital or acquired deficiency of the ultra large von Willbrand's factor (ULVWF) cleavage protease. It is characterized by mechanical micro angiopathic hemolytic anemia, and organ dysfunctions.

Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children

Thrombotic thrombocytopenic purpura (TTP) related to a severely deficient activity of the von Willebrand factor cleaving protease, ADAMTS (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats) 13, is a life-threatening event, the onset of which may occur as early as childhood. TTP is either inherited (Upshaw-Schulman syndrome) via ADAMTS13 gene mutations (neonatal onset) or acquired via anti-ADAMTS13 autoantibodies (childhood onset). TTP is due to platelet- and von-Willebrand-factor-rich thrombi of the microvasculature, inducing mechanical hemolytic anemia, consumption thrombocytopenia, and multivisceral ischemia. Clinical course consists of relapsing acute events triggered mostly by infections, associated icterus and hyperbilirubinemia, severe hemolytic anemia with schistocytosis and a negative Coombs test, severe thrombocytopenia, and sometimes symptoms related to visceral ischemia (renal failure, central nervous system vascular events, other organ failure). The recently available ADAMTS13 laboratory investigation combining measurement of ADAMTS13 activity in plasma, search for an ADAMTS13 circulating inhibitor, and anti-ADAMTS13 IgG and ADAMTS13 gene sequencing is a crucial addition to TTP diagnosis. Plasma exchanges are first-line treatment of acquired TTP, combined with steroids and immunosuppressive drugs. Curative treatment of acute events in Upshaw-Schulman syndrome relies on plasma infusions (provider of active ADAMTS13). Guidelines for preventive treatment of relapses are not clearly established but should associate plasmatherapy and caution to triggers of relapses. Therapeutic perspectives are focused on the development of concentrated plasma-derived ADAMTS13 or recombinant ADAMTS13.

Haemolytic uraemic syndrome

Haemolytic Uraemic Syndrome (HUS) is characterised by haemolytic anaemia, thrombocytopenia and acute renal failure in the absence of disseminated intravascular coagulation. Thrombosis in the microcirculation with consumptive thrombocytopenia and mechanical haemolytic anaemia with fragmented red cells results in ischaemic organ damage. The kidney is the organ predominantly affected but extra-renal manifestations may occur. Central nervous system involvement may cause seizures, altered consciousness, hemiparesis and brain stem dysfunction. Cardiomyopathy, liver dysfunction and diabetes are all recognised. Prodromal diarrhoea occurs in 90–95% of cases. This is referred to as typical or D + HUS. Young children are most commonly affected. Infection with shiga-like toxin producing E. coli is the most important risk factor. There is good evidence that the toxin plays a key role in pathogenesis. The 5% of cases in which there is no diarrhoeal prodrome are referred to as atypical HUS (aHUS). The mortality in the acute phase of D + HUS varies between 2 and 12% being higher in outbreaks. The mortality in the acute phase of aHUS is much higher at around 20%. Recent advances in understanding have led to the recognition of abnormalities of complement regulation, abnormal circulating von Willebrand factor multimers, infections and drugs as causes of atypical HUS.

Paroxysmal Nocturnal Hemoglobinuria: An Historical Overview

The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is episodic hemoglobinuria, and it was this feature that captured the attention of European physicians in the latter half of the 19th century, resulting in careful observational studies that established PNH as an entity distinct from paroxysmal cold hemoglobinuria and march hemoglobinuria. Curiosity about the etiology of the nocturnal aspects of the hemoglobinuria led the German physician Paul Strübing to develop the prescient hypothesis that the erythrocytes of PNH are abnormally sensitive to hemolysis when the plasma is acidified during sleep because of accumulation of carbon dioxide and lactic acid as a result of slowing of the circulation. Investigation of the intricate pathophysiology that underlies the abnormal sensitivity of PNH erythrocytes to hemolysis in acidified serum produced a number of remarkable scientific achievements that involved discovery of the alternative pathway of complement, identification of the membrane proteins that regulate complement, discovery of a novel mechanism for attachment of proteins to the cell surface, and identification of the genetic basis of the disease. These discoveries were made steadily over a period of more than 100 years, and each generation of physicians and scientists made important contributions to the field. The mysteries of PNH have been solved in a particularly satisfying way because the precision and orderliness of the solutions made clearly understandable what had seemed at the times prior to resolution to be problems of nearly insurmountable complexity. The history of PNH is an inspirational reminder of the elegant complexity of nature, the rewards of curiosity and the power and beauty of science.

Intravascular Hemolysis and Mean Red BloodCell Age in Athletes

Since the observation that mechanical stress causes red blood cell (RBC) destruction, foot-strike hemolysis has been used to explain sports anemia and RBC rejuvenation in athletes. Recently gained knowledge questions the importance of mechanical RBC trauma on RBC hemolysis in athletes. Male athletes (N = 90) and untrained male controls (N = 58) were investigated for aerobic performance, hematological parameters, serum erythropoietin concentration (EPO), soluble transferrin receptor concentration (sTFR), and erythrocyte aspartate aminotransferase activity (eAST). On hard floor running disciplines (HFR, N = 26, short- and long-distance runners, triathletes) showed a lower eAST (P < 0.001) and thus no younger RBC population than not on hard floor running athletes (NHFR, N = 64, cyclists, soccer players, others) or the untrained control group (N = 58). HFR had higher but still normal EPO (P < 0.01) and no higher sTFR. Because intravascular hemolysis occurs in swimmers, cyclists, and runners, and mean RBC age is not reduced in runners, mechanisms other than foot-strike hemolysis have to be considered as well. Possible reasons are intramuscular destruction, osmotic stress, and membrane lipid peroxidation caused by free radicals released by activated leukocytes. Intravascular hemolysis can even be regarded as physiological means to provide heme and proteins for muscle growth.

Microangiopathies thrombotiques : physiopathologie, diagnostic et traitement

Thrombotic microangiopathies (TMA) consist in a syndrome characterized by a mechanical hemolytic anemia, a consumption thrombocytopenia and multivisceral ischemia. Thrombotic thrombocytopenic purpura (TTP) is a multisystemic form of TMA which prognosis may be severe; hemolytic uremic syndrome (HUS) is a TMA which renal involvement is predominant. A TMA syndrome may also be observed in association with other clinical contexts such as the HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome, cancers, organ transplantations, Human Immunodeficiency Virus infection, catastrophic antiphospholipid syndrome or severe disseminated intravascular coagulation. The pathophysiology for TMA has been recently better elucidated, allowing a more appropriate classification of the various forms of this syndrome. TTP is characterized by a severe enzymatic deficiency of the specific von Willebrand factor (VWF)-cleaving protease named ADAMTS13; this deficiency which is either acquired via autoantibodies or inherited via ADAMTS13 gene mutations, leads to the accumulation of hyperadhesive forms of VWF in plasma inducing the spontaneous formation of platelet thrombi in the microvasculature. Pathophysiology for HUS may involve either verotoxin-producing bacteria (post-diarrheal HUS) or inherited complement proteins deficiencies (factor H, factor I, CD46/MCP-1). Diagnosis and therapeutic management of TMA both remain an emergency. The first intention treatment is plasmatherapy (mainly plasma exchanges) while immunosuppressive drugs, specific treatment for an underlying disease and intensive care procedures may be required as a function of the clinical context. The global prognosis of TMA remains difficult to establish considering the heterogeneity of the different forms of this syndrome.

Changes in erythropoiesis assessed by reticulocyte parameters during ultralong distance running.

To investigate the possibility of early changes in erythropoiesis during prolonged exercise being reflected in reticulocyte parameters. This was a case-control field study of hematological variables in a group of ultramarathon runners competing in a 6-day track race. A 6-day ultramarathon in Colac, Australia. 7 male and 1 female experienced ultramarathon runners. A track race of 6 days' duration. A wide range of red cell and reticulocyte parameters. Resting red cell parameters were within normal clinical limits. However, except for the expected findings typical of hemodilution, red cell parameters were relatively unchanged during and after the event, with the exception of small but statistically significant changes in number and percentage of macrocytic, microcytic, hypochromic, and hyperchromic red cells. No reticulocytosis was found in an event that would have been expected to be associated with significant foot-strike hemolysis; however, an increase in the percentage of reticulocytes with high RNA content late in the event indicates early release from the marrow. Reduction in reticulocyte mean cell volume, which is consistent with functional iron deficiency, was demonstrated during the event. This finding is consistent with changes in some of the iron-related parameters associated with the acute phase response, but the dissociation in time between these changes makes a causal relationship unlikely. Other changes such as those in reticulocyte hemoglobin distribution width, reticulocyte distribution width, cell hemoglobin concentration mean, and lack of change in corpuscular hemoglobin are not typical of true iron deficiency, and the mechanism of these changes is currently unknown. The hematopoietic system demonstrates remarkable stability in the face of very significant exercise stress. No reticulocyte response was demonstrated in this study, but reticulocyte changes both consistent with and contrary to early release from the marrow were demonstrated after several days of strenuous running. The significance of several newly developed ratios of red cell and reticulocyte parameters in conditions of exercise stress requires further investigation.

Acute renal failure in a marathon runner: role of glomerular bleeding intubular injury

Hematuria is a well recognized and generally benign consequence of sports activity, especially running a marathon (1). A few cases of acute renal failure in long-distance runners have been described due to rhabdomyolysis or less frequently to hemolysis (march hemoglobinuria) (1–3). We report the case of a marathon runner who presented with gross hematuria and anuric renal failure that we considered to be due to tubular injury from glomerular bleeding, similar to that seen in IgA nephropathy (4).

Sport-related hematuria: a review.

To present an overview and models of the potential causes and implications of sport-related hematuria in an athletic population as provided by a literature review. A total of 64 published scientific articles have been utilized to provide a review of sport-related hematuria. Reviewed studies were selected on the basis that they provided informative findings about the possible mechanisms of sport-related hematuria attributed to exercise duration and intensity. These studies used both normal adult and athletic populations. A review of the literature on the potential mechanisms of sport-related hematuria led to the classification of these mechanisms as either exercise duration related or exercise intensity related. Research has revealed an increased prevalence of hematuria in athletes. The mechanisms responsible may be traced to different sources or a combination thereof. Many explanations have been directed toward a potential cause; foot-strike hemolysis, renal ischemia, hypoxic damage to the kidney, the release of a hemolyzing factor, bladder and/or kidney trauma, nonsteroidal anti-inflammatory drugs, dehydration, increased circulation rate, myoglobinuria release, and the peroxidation of red blood cells. These mechanisms are presented in two models depicting the influence of either exercise intensity or exercise duration on sport-related hematuria. Athletes, coaches, and sports medicine professionals should be aware of this condition because frequent high-intensity and/or long-duration workouts and competitions may promote the symptoms. Repeated red blood cell loss through the urine may be a contributing factor toward promoting anemic conditions in competitive athletes. Recognition of the potential mechanisms can spare the time and expense of invasive testing.

A case report of mechanical hemolytic anemia after mitral annuloplasty with Carpentier's ring

A case report of mechanical hemolytic anemia after mitral annuloplasty with Carpentier's ring

Hematologic and Hemostatic Complications Associated with Long‐Term Use of Total Artificial Heart: Clinical and Experimental Observations

The two most serious complications associated with long-term use of a total artificial heart (TAH) are thromboembolism and infection. In this article, we review our experience in one patient implanted with a pneumatic TAH for 396 days, and in 24 calves implanted with the same type of device for 70 to 353 (median 150) days. During his survival with the TAH, our patient suffered several thromboembolic episodes despite adequate anti-coagulation with warfarin. Autopsy showed widespread thrombotic lesions, mostly in the brain. Throughout his survival, the patient had markedly elevated plasma beta-thromboglobulin and fibrinopeptide A levels, indicating sustained activation of platelets and the coagulation system secondary to blood contact with the artificial surface. Long-term use of TAH in calves causes significant mechanical hemolytic anemia and a small reduction in the total leukocyte and neutrophil counts. The platelet count normalized to preimplantation levels by 25 to 35 weeks. At autopsy, thrombotic lesions and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. Although impressive gains in the clinical and experimental use of TAH were achieved during the last 15 years, thromboembolism and infection remain challenging problems.

A case of fatal mechanical hemolytic anemia following surgical patch closure of ventricular septal defect

A case of fatal mechanical hemolytic anemia following surgical patch closure of ventricular septal defect

Development of Runner's Anemia during a 20-Day Road Race: Effect of Iron Supplements

Intense training for long-distance running has been associated with reduced hemoglobin (Hb) levels and low iron stores. Whether iron supplementation helps prevent this "runner's anemia" remains controversial. To determine the relationship between iron status and the early stage of reduced Hb levels in male runners, we examined hematologic variables in 15 healthy men (ages 25 to 47 yrs) who ran twice their regular training distance in 20 days during a 500-km road race. Nine of the runners took iron-containing tablets which provided an average of 36 mg/d of iron, while the other six did not take iron supplements. Only one of the 15 subjects had a low Hb concentration (less than 14 g/dl) before the race. After 10 days (285 km), low Hb levels (p less than 0.001) were found in 12/15; six of these runners took iron supplements. However, following a 2-day rest period and five more days of running, only 5/15 and 7/15, respectively, had low Hb levels. Serum iron, ferritin, total iron binding capacity, and percent transferrin saturation values remained within normal limits and did not change significantly. Reticulocyte counts progressively increased, becoming 8-fold higher than at baseline (p less than 0.001), irrespective of the use of iron supplements. "Runner's anemia" developed in 11/15 (73%) of the subjects, independently of their iron status and iron intake. The reductions in Hb were accompanied by parallel decreases in RBC count and hematocrit, and by a significant reticulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of 7 Successive Days of Unaccustomed Prolonged Exercise on Aerobic Performance and Tissue Damage in Fitness Joggers*

The effects of 7 successive days of prolonged jogging on aerobic performance and biochemical markers of muscle and red blood cell damage were examined in 10 moderately fit men, ages 27 +/- 2 yr (mean +/- SE). The subjects jogged for 2 h per day at 78 +/- 4% of maximal heart rates and covered a total of 129 +/- 2 km, nearly eight times their regular weekly training distance. At baseline, maximal oxygen uptake (VO2max) during treadmill tests averaged 3.45 +/- 0.24 L/min, or 44.7 +/- 1.4 ml/kg/min. On follow-up tests 2d after the week of increased training, VO2max (3.56 +/- 0.17 L/min) and treadmill performance were not significantly improved. Body weight declined from 79.5 +/- 4.6 kg to 77.8 +/- 4.4 kg (p less than 0.05) because of reduced body fatness (16.8 +/- 2.3% to 13.6 +/- 1.7%, p less than 0.05). Weight-adjusted VO2max increased to 46.4 +/- 2.0 ml/kg/min (p less than 0.05). However, heart rate and systolic blood pressure were not significantly changed at rest, or during submaximal and maximal treadmill exercise. Mean hemoglobin concentration at treadmill testing declined from 14.9 +/- 0.3 g/dl to 13.3 +/- 0.3 g/dl (p less than 0.05). Leg muscle soreness, especially in the thigh region, persisted in all subjects after 3 d. Soreness was accompanied by chronic elevations (p less than 0.05) in serum levels of myoglobin, creatine kinase (CK), lactic dehydrogenase (LD), aminoaspartate, and the isoenzymes CK-MB and LD1,2. Serum haptoglobin levels after jogging fell from 86 +/- 9 mg/dl to 60 +/- 8 mg/dl (p less than 0.05), suggestive of footstrike hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sports Hematuria

Strenuous exercise makes extraordinary demands. The transition from rest to intensive physical activity can cause pathological changes in various organs, particularly in the urinary tract. Hematuria (microscopic or macroscopic) is one of the abnormalities commonly found after sports activity. This phenomenon can occur in noncontact sports (such as rowing, running and swimming) as well as in contact sports (boxing, football and so forth). The pathophysiology can be either traumatic or nontraumatic. Renal trauma and/or bladder injury due to repeated impact of the posterior bladder wall against the bladder base can cause vascular lesions and consequently hematuria. There are 2 mechanisms of nontraumatic injury. 1) Vasoconstriction of the splanchnic and renal vessels occurs during exercise in order that blood can be redistributed to the contracting skeletal muscles, thus causing hypoxic damage to the nephron. This results in increased glomerular permeability which would favor increased excretion of erythrocytes and protein into the urine. 2) A relatively more marked constriction of the efferent glomerular arterioli results in an increased filtration pressure, which favors increased excretion of protein and red blood cells into the urine. It must be noted that sports hematuria differs from other conditions that may cause reddish discoloration of the urine due to physical exercise, such as march hemoglobinuria and exercise myoglobinuria. In the latter 2 abnormalities there is excretion of hemoglobin and myoglobin molecules in the urine and not whole blood or intact red blood cells. Sports hematuria usually has a benign self-limited course. However, coexisting urinary tract pathological conditions should be excluded carefully.