Endothelial dysfunction in patients with hereditary spherocytosis and b-thalassemia

Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.

Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature

Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.

Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria

Background Plasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinoline drugs that can provoke threatening acute hemolytic anemia in patients having an X-linked G6PD-deficiency. Heterozygous females may screen as G6PD-normal prior to radical cure and go on to experience hemolytic crisis. Methods & findings This study examined G6PD phenotypes in 1928 female subjects living in malarious Sumba Island in eastern Indonesia to ascertain the prevalence of females vulnerable to diagnostic misclassification as G6PD-normal. All 367 (19%) females having <80% G6PD normal activity were genotyped. Among those, 103 (28%) were G6PD wild type, 251 (68·4%) were heterozygous, three (0·8%) were compound heterozygotes, and ten (2·7%) were homozygous deficient. The variants Vanua Lava, Viangchan, Coimbra, Chatham, and Kaiping occurred among them. Below the 70% of normal G6PD activity threshold, just 18 (8%) were G6PD-normal and 214 (92%) were G6PD-deficient. Among the 31 females with <30% G6PD normal activity were all ten homozygotes, all three compound heterozygotes, and just 18 were heterozygotes (7% of those). Conclusions In this population, most G6PD heterozygosity in females occurred between 30% and 70% of normal (69·3%; 183/264). The prevalence of females at risk of G6PD misclassification as normal by qualitative screening was 9·5% (183/1928). Qualitative G6PD screening prior to 8-aminoquinoline therapies against P. vivax may leave one in ten females at risk of hemolytic crisis, which may be remedied by point-of-care quantitative tests.

MO218ALTERNATING EPISODES OF TRUE HYPERKALEMIA AND PSEUDOHYPERKALEMIA IN ADULT SICKLE CELL DISEASE - A NEPHROLOGIST'S DILEMA

Background and Aims To illustrate the phenomenon of alternating true hyperkalemia and pseudohyperkalemia in adult sickle cell disease. Method Case Report Results Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease and renal manifestations include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Furthermore, acute hemolytic crisis can be complicated by sepsis. Hemolysis, specifically, intravascular hemolysis, can produce hyperkalemia. Additionally, reduced glomerular filtration rate from SCN predisposes to hyperkalemia. Pseudo-hyperkalemia was first reported by Hartmann and Mellinkoff in 1955 as a marked elevation of serum potassium levels in the absence of clinical evidence of electrolyte imbalance. In pseudohyperkalmia, simultaneously estimated serum potassium exceeds plasma potassium by &gt;0.4 mmol/L. This is often associated with moderate to severe thrombocytosis or leukocytosis. Clearly, hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate treatment of pseudo-hyperkalemia leading to hypokalemia is also equally potentially lethal. We describe a 40-yo African American male patient with sickle cell anemia who exhibited alternating episodes of hyperkalemia and pseudo-hyperkalemia, during consecutive hospital admissions. Pseudohyperkalemia was associated with severe thrombocytosis complicating sepsis. EKG was normal despite measured serum potassium of 6.7 mmol/L (Figure). Conclusion We believe that this is the first report of adult SCD demonstrating alternating cycles of true hyperkalemia and pseudo-hyperkalemia at different times. We must draw attention to the new availability of the new potassium binders, Patiromer and sodium zirconium cyclosilicate. We would advocate for caution in the use of these potent potassium binders and to always give consideration to the presence of pseudo-hyperkalemia under appropriate clinical scenarios. We posit that providers managing adult patients with sickle cell disease must be aware of such a phenomenon to avoid the dangers of overtreatment of episodes of pseudo-hyperkalemia in such patients.

Alternating and Concurrent True Hyperkalemia and Pseudohyperkalemia in Adult Sickle Cell Disease

Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.

Chronic copper poisoning in beef cattle in the state of Mato Grosso, Brazil

ABSTRACT: Copper is an essential micromineral in animal feed; however, when consumed in excess, it can cause liver necrosis, hemolytic crisis, hemoglobinuric nephrosis and death in cattle. Although uncommon in this species, copper poisoning occurs as a result of exacerbated supplementation, deficiency of antagonist microminerals, or previous liver lesions. An outbreak of chronic copper poisoning is reported in semi-confined cattle after supplementation with 50 mg/Kg of dry matter copper. The cattle showed clinical signs characterized by anorexia, motor incoordination, loss of balance, jaundice, brownish or black urine, diarrhea and death, or were found dead, 10 to 302 days after consumption. Of the 35 cattle that died, 20 underwent necropsy, whose frequent findings were jaundice, enlarged liver with evident lobular pattern, black kidneys, and urinary bladder with brownish to blackish content. Microscopically, the liver showed vacuolar degeneration and/or zonal hepatocellular centrilobular or paracentral coagulative necrosis, in addition to cholestasis, mild periacinal fibrosis, apoptotic bodies, and mild to moderate mononuclear inflammation. Degeneration and necrosis of the tubular epithelium and intratubular hemoglobin cylinders were observed in the kidneys. Copper levels in the liver and kidneys ranged from 5,901.24 to 28,373.14 μmol/kg and from 303.72 to 14,021 μmol/kg, respectively. In conclusion, copper poisoning due to excessive nutritional supplementation is an important cause of jaundice, hemoglobinuria, and death in semi-confined cattle.

Acute kidney injury with dark urine: the case of paroxysmal nocturnal hemoglobinuria

In this case report; we describe a patient with severe attack of paroxysmal nocturnal hemoglobinuria (PNH) following Ciprofloxacin therapy. He presented with recurrent abdominal pain, repeated vomiting and dark urine. Physical examination revealed severe pallor and jaundice. Laboratory investigations showed severe intravascular hemolysis with negative Coomb’s test, progressive acute kidney injury (AKI), sterile blood cultures and negative serology for autoimmune diseases. Subsequently, he developed pancytopenia. Ham test was positive and flow cytometry, later on, confirmed PNH. He was supported with multiple transfusions of packed blood cells and hemodialysis. Ciprofloxacin was discontinued and his PNH was treated with Solumedrol 1 g daily for 3 days followed by Prednisone 60 mg/day for 2 months. Two weeks later; his hemolysis abated and his AKI improved. Up to 5 years later, he still has minor PNH clone yet without disease activity. In conclusion; our patient had acute drug-induced hemolytic crisis associated with minor PNH clone. With drug-vigilance; no further relapses were reported and his PNH clone remained stable for 5 years. The case expands the spectrum of PNH phenotypes and its triggering factors. Keywords: AKI, anemia, autoimmune, flow cytometry, hemolysis, PNH.