Severe Hemolytic Anemia and Metabolic Acidosis at Birth with Glutathione Synthetase Deficiency and Progressive Neurological Symptoms on Follow-Up.

BACKGROUND Glutathione synthetase deficiency (GSD) is a rare autosomal recessive disorder caused by glutathione synthetase (GSS) gene variants that occur in 1 in 1 million individuals. The severe form of GSD is characterized by hemolytic anemia, metabolic acidosis with 5-oxoprolinuria, progressive neurological symptoms, and recurrent bacterial infections. This case report presents a male Japanese infant with severe hemolytic anemia and metabolic acidosis at birth caused by GSD, who developed progressive neurological symptoms on follow-up. CASE REPORT A Japanese male term infant developed severe hemolytic anemia and metabolic acidosis in the early neonatal period. We suspected GSD based on his symptoms and a high 5-oxoproline urine concentration. We began correcting his metabolic acidosis and administering vitamins C and E supplements. The patient required blood transfusion twice during the acute phase for hemolytic anemia. After age 1 month, he maintained good control of metabolic acidosis and hemolytic anemia. A definitive diagnosis of GSD was made based on high concentrations of 5-oxoproline in urine, low concentrations of glutathione and GSS activity in erythrocytes, and genetic testing. Several episodes of febrile convulsions were started at age 11 months, but none occurred after 2 years. At the last follow-up at age 25 months, metabolic acidosis and hemolytic anemia were well controlled, but he had mild neurodevelopmental delay. CONCLUSIONS This case report shows that GSD can present with severe hemolytic anemia and metabolic acidosis at birth, and manifest with subsequent neurological impairment despite early diagnosis and treatment. Therefore, a careful long-term follow-up that includes neurological evaluation is essential for patients with GSD.

Intractable mechanical hemolytic anemia complicating mitral valve surgery: a case series study.

BACKGROUND: Intractable, mechanical hemolytic anemia (IMHA) is a rare catastrophic complication following mitral valve surgery. We analyzed patient characteristics and IMHA management by reoperations after mitral valve surgery. METHODS: We collected medical records from mitral valve patients requiring reoperation due to IMHA. INCLUSION CRITERIA: hemoglobin < 100 g/L; positive hemolysis tests and echocardiography results; and exclusion of other hemolysis causes. RESULTS: Data from 25 IMHA cases included 10 (40%) early onset (1.3 (0.3,3.0) months) and 15 (60%) late onset (120 (24,204) months) cases. Early IMHA etiologies included surgical defects (6, 60%), uncontrolled infection (3, 30%) and Bechet's disease (1, 10%). Late IMHA etiologies included degeneration (13, 87%), new infection (1, 7%) and trauma (1, 7%). There were more mechanical valves (15, 88%) than bio-valves (2, 12%); the main valvular dysfunction was paravalvular leak (16, 64%). IMHA manifestations included jaundice (18, 72%), dark urine (21, 84%), heart failure (16, 64%), acute kidney injury (11, 44%), hepatomegaly (15, 60%), splenomegaly (15, 60%) and pancreatitis (1, 4%). Laboratory results showed decreased hemoglobin (70 ± 14 g/L) and increased bilirubin (72 ± 57 µmol/L), lactate dehydrogenase (2607 ± 2142 IU/L) and creatinine (136 ± 101 µmol/L) levels. Creatinine level negatively correlated with hemoglobin level (B = -3.33, S.E. B = 1.31, Exp(B) = 368.15, P = 0.018). Preoperative medications included iron supplements (20, 80%), erythropoietin (16, 64%) and beta-blocker (22, 88%). Two patients died of cardiac causes before reoperation. The other 23 underwent reoperation with long surgical times (aortic cross clamp 124 ± 50 min, cardiopulmonary bypass 182 ± 69 min) and blood transfusions (red blood cells 6 (6, 8) units, plasma 600 (400,800) ml, platelet 1(0,2) units). Postoperative complications included cardiac dysfunction (5, 22%), arrhythmia (10, 43%), sepsis (6, 26%), pulmonary infection (5, 22%), gastrointestinal bleeding (3, 13%), cerebral hemorrhage (2, 9%), chronic renal dysfunction (1, 4%) and surgical hemorrhage (1, 4%). Five (33%) patients died after reoperation from cardiac dysfunction (3, 60%), septic shock (1, 20%) and self-discharge (1, 20%). CONCLUSIONS: IMHA induces severe multi-organ dysfunction, contributing to high mortality. Perioperative management should focus on etiological treatment, organ protection, and blood management.

Successful management of Heinz body hemolytic anemia associated with leek (Allium ampeloprasum) ingestion in a South American coati (Nasua nasua).

OBJECTIVE: To describe the diagnosis, management, and outcome of Heinz body hemolytic anemia in a South American coati (Nasua nasua) secondary to suspected leek (Allium ampeloprasum) toxicosis. CASE SUMMARY: A South American coati presented with Heinz body hemolytic anemia following addition of leeks to its diet for 2-5 days prior to initial presentation. Administration of a whole blood transfusion from an animal of the same species (conspecific) and supportive care resulted in immediate improvement in clinical signs. Normal behavior fully returned within 6 days of transfusion. Hematological evidence of anemia resolved by 4 weeks and there were no significant features of oxidative injury present by 8 weeks following initial presentation. NEW INFORMATION PROVIDED: This is the first reported case of Heinz body hemolytic anemia, suspected leek toxicosis, and administration of a blood transfusion in this species.

Serum Folate Levels in Patients with Chronic Hemolytic Anemia on Regular Folic Acid Supplementation Before and After Dose Modification.

OBJECTIVE: In light of the recommendation of folic acid supplementation in chronic hemolytic anemia, with possible supratherapeutic dosing and associated side effects, we performed this study to investigate serum folate levels in children with chronic hemolytic anemia. METHODS: Phase 1 was a cross-sectional study of 134 patients in the Pediatric Hematology service, documenting daily dosage and performing serum folate levels. In phase 2, we reduced the dose to 1 mg for 148 patients and repeated the testing after six months. RESULTS: We found very high serum folate levels with Phase 1, with 93.2% above the upper level of normal. In Phase 2, values remained high with 42.5% above the acceptable upper limit. CONCLUSION: Doses of folic acid given to sickle cell and thalassemia patients exceed their actual needs. This should be re-evaluated to strike a balance between benefit and harm, with close monitoring of serum folate levels.

Hemolytic anemia caused by non-D minor blood incompatibilities in a newborn.

Hyperbilirubinemia is one of the most widely seen cause of neonatal morbidity. Besides ABO and Rh isoimmunization, minor blood incompatibilities have been also been identified as the other causes of severe newborn jaundice. We report a newborn with indirect hyperbilirubinemia caused by minor blood group incompatibilities (P1, M, N, s and Duffy) whose hemolysis was successfully managed with intravenous immunoglobulin therapy. A thirty-two gestational weeks of preterm male baby became severely icteric on postnatal day 11, with a total bilirubin level of 14.66 mg/dl. Antibody screening tests revealed incompatibility on different minor groups (P1, M, N, s and Duffy (Fya ve Fyb)). On postnatal day thirteen, the level of bilirubin increased to 20.66 mg/dl although baby was under intensive phototherapy. After the administration of intravenous immunoglobulin and red blood cell transfusion, hemoglobin and total bilirubin levels became stabilised. Minor blood incompatibilities should be kept in mind during differential diagnosis of hemolytic anemia of the newborn. They share the same treatment algorithm with the other types hemolytic anemia. New studies revealed that intravenous immunoglobulin treatment in hemolytic anemia have some attractive and glamorous results. It should be seriously taken into consideration for treatment of minor blood incompatibilities.

Efficacy of L-carnitine on ribavirin-induced hemolytic anemia in patients with hepatitis C virus infection.

BACKGROUND/AIMS: L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease. METHODS: A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires. RESULTS: A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment. CONCLUSION: L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.

Vitamin C deficiency: rare cause of severe anemia with hemolysis.

Historically known to be a disease of sailors and soldiers in the seventeenth and eighteenth century, scurvy is a rare nutritional deficiency in the developed world, but it can still be seen among the alcoholics and the malnourished. We present a case of a 39-year-old alcoholic male who presented with progressive fatigue and diffuse purpuric rash with scattered ecchymosis for 2 months. Blood work was remarkable for hemoglobin of 9.1 g/dl, which further dropped to 7 g/dl over the next few days. He was then found to have hemolysis on lab work. After an extensive workup, the common causes of hemolytic anemia were ruled out, vitamin C level was checked, which interestingly resulted as 0 mg/dl. Supplementation with oral vitamin C resulted in the gradual resolution of hemolytic anemia and rash. Hemoglobin improved to 15 g/dl in 4 weeks, with normalization of vitamin C level. The clinical features of scurvy can easily be confused with conditions such as vasculitis, deep venous thrombosis, and systemic bleeding disorders. Therefore, comprehensive workup up is required prior to the diagnosis. Although rare, being a reversible condition, early diagnosis and treatment of scurvy in high-risk populations cannot be stressed enough.

Microangiopathic haemolytic anaemia with thrombocytopenia induced by vitamin B12 deficiency long term after gastrectomy.

Microangiopathic haemolytic anaemia with thrombocytopenia, called pseudo-thrombotic microangiopathy (TMA), is a clinically important complication in patients with vitamin B12 deficiency. We herein present a case of an 80-year-old woman with pseudo-TMA after gastrectomy. She was initially suspected with thrombotic thrombocytopenic purpura based on rapid progression of anaemia with schistocytes and thrombocytopenia; however, her anaemia and thrombocytopenia were improved by vitamin B12 supplementation alone, with a single session of plasma exchange. Vitamin B12 deficiency was finally confirmed by low vitamin B12 levels from the patient's initial blood sample. In addition, normal ADAMTS13 activity was proven, lowering the likelihood of thrombotic thrombocytopenic purpura. Therefore, this patient was diagnosed with pseudo-TMA caused by vitamin B12 deficiency. Pseudo-TMA can occur in patients with vitamin B12 deficiency post-gastrectomy.

[How I do in front of an hemolytic anemia of unknown etiology?] / Que faire devant une anémie hémolytique sans étiologie retrouvée ?

The most frequent causes of hemolytic anemias are immune or infectious diseases, drug induced hemolysis, thrombotic microangiopathies, hereditary spherocytosis, glucose-6-phosphate dehydrogenase or pyruvate kinase deficiencies, thalassemia's and sickle cell disease. Sometimes no cause is found because a rarer etiology is involved. The goal of this review is to remember some unfrequent constitutional or acquired causes and to point out difficulties to avoid wrong interpretations of analysis results.

Neonatal management and outcome in alloimmune hemolytic disease.

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management. Areas covered: This review focusses on the current neonatal management and outcome of hemolytic disease and discusses postnatal treatment options as well as literature on long-term neurodevelopmental outcome. Expert commentary: Despite major advances in neonatal management, multiple issues have to be addressed to optimize postnatal management and completely eradicate kernicterus. Except for strict adherence to guidelines, improvement could be achieved by clarifying the epidemiology and pathophysiology of HDFN. Several pharmacotherapeutic agents should be further researched as alternative treatment options in hyperbilirubinemia, including immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in neonates. Long-term follow-up studies are needed in HDFN, especially on thrombocytopenia, iron overload and cholestasis.

Modelling primaquine-induced haemolysis in G6PD deficiency.

Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent.

Variable Clinical Presentations of ABO Incompatibility in Dizygotic Twins.

Newborns with ABO blood group incompatibility can have a spectrum of clinical presentations from remaining asymptomatic to severe hemolytic anemia with jaundice. This case presentation discusses dizygotic twins who demonstrated both ends of the clinical spectrum. Similar cases in which there is such extreme variation between twins were not attainable in the current literature, which prompted the authors to present it as a rare occurrence and one that was unexpected based on their past experience with ABO incompatibility both in singletons and in twins.

Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

Oxidant-induced damage to equine erythrocytes from exposure to Pistacia atlantica, Pistacia terebinthus, and Pistacia chinensis.

Two horses were referred for methemoglobinemia and hemolytic anemia following 5 acute deaths in their herd from an unidentified toxin source. Horses have a greater risk than other mammalian species of developing methemoglobinemia and hemolytic anemia following ingestion of oxidizing toxins, due to deficiencies in the mechanisms that protect against oxidative damage in erythrocytes. Their susceptibility to oxidative erythrocyte damage is evident in the numerous cases of red maple (Acer rubrum) toxicosis. The suspected toxins causing A. rubrum toxicosis are tannic acid, gallic acid, and a metabolite of gallic acid, pyrogallol. These compounds can be found in a variety of plants, posing a risk to equine health. In order to quickly identify toxin sources, 2 rapid in vitro assays were developed to screen plant extracts for the ability to induce methemoglobin formation or cause hemolysis in healthy equine donor erythrocytes. The plant extract screening focused on 3 species of the genus Pistacia: P. atlantica, P. terebinthus, and P. chinensis, which were located in the horse pasture. Extracts of the seeds and leaves of each species induced methemoglobin formation and resulted in hemolysis, with seed extracts having greater potency. The in vitro assays used in the current study provide a useful diagnostic method for the rapid identification of oxidizing agents from unidentified sources. There is no effective treatment for oxidative erythrocyte damage in horses, making rapid identification and removal of the source essential for the prevention of poisoning.

Neonatal hemolytic anemia due to pyknocytosis.

UNLABELLED: A newborn boy was referred to our hospital because of hemolytic anemia and severe hyperbilirubinemia. Extensive investigations aimed at determining the cause of hemolysis was initiated at the time of admission and 3 months after blood transfusion. Notably, no intrinsic erythrocyte abnormalities could be detected. The only possible cause explaining the progressive anemia and unconjugated hyperbilirubinemia was the finding of pyknocytes, severely distorted erythrocytes, on the blood film at hospital admission. We propose a role for an increased free fraction of plasma unconjugated bilirubin in the formation of pyknocytes through bilirubin membrane toxicity with subsequent anemia and progressive hyperbilirubinemia. CONCLUSION: Pyknocytosis is a transitory erythrocyte-related condition which can result in severe anemia and hyperbilirubinemia. Recognition of pyknocytes by microscopic analysis of a blood film is essential for a correct diagnosis. Treatment consists of correction of the anemia by top-up blood transfusion and light therapy to prevent toxic bilirubin buildup. High levels of free unconjugated bilirubin could be the underlying cause for the formation of pyknocytes.

Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity.

Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.

Haemolytic anaemia after ingestion of Neem (Azadirachta indica) tea.

The authors report a clinically relevant and possible cause of haemolytic anaemia from ingestion of a Mexican tea from the Neem tree, also known as Azadirachta indica, in a 35-year-old Hispanic man who was found to have glucose-6-phosphate dehydrogenase deficiency.

What caused hemolytic anemia and colicky abdominal pain? Lead!

No abstract available.