Occurrence of a paroxysmal nocturnal hemoglobinuria clone in an essential thrombocythemia: a link between PIGV and MPL (original) (raw)
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The Hematology Journal, 2000
The association of paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) raises the yet unresolved questions as t o whether these two disorders are different forms of the same disease. We compared two groups of patients with respect t o cytogenetic features, glycosylphosphatidylinositol (GPII-linked protein expression, protein C/ protein Slthrombomodulinlantithrombin 111 activity, and PIG-A gene expression. The first group consisted of eight patients with PNH (defined as positive Ham and sucrose tests at diagnosis), and the second, 37 patients with AA. Twelve patients with AA later developed a PNH clone. Monoclonal antibodies used t o study GPI-linked protein expression (CD14 [on monocytesl, CD16 [on neutrophils], CD48 [on lymphocytes and monocytes], CD67 [on neutrophils and eosinophils], and, more recently, CD55, 0 5 8 , and CD59 [on erythrocytesl) were also tested on a cohort of 20 normal subjects and five patients with constitutional AA. Ham and sucrose tests were performed on the same day as flow-cytometric analysis. Six of 12 patients with A A , who secondarily developed a PNH clone, had clinical symptoms, while all eight patients with PNH had pancytopenia and/or thrombosis andlor hemolytic anemia. Cytogenetic features were normal in all but t w o patients. Proteins C and S, thrombomodulin, and antithrombin 111 levels were within the normal range in patients with PNH and in those with AA (with or without a PNH clone). In patients with PNH, CD16 and CD67 expression were deficient in 78% t o 98% of the cells and CD14 in 7696 t o 100Y0. By comparison, a GPI-linked defect was detected in 13 patients with AA, affecting a mean of 32% and 33% of CD16/CD67 and CD14 cell populations, re-CQUIRED APLASTIC ANEMIA (AA) is a heterogeneous disease, in which several pathophysiologic factors are involved.' In contrast to patients who undergo bone marrow transplantation (BMT), those who are successfully treated with immunosuppressive therapy (IST) are at risk for subsequently developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndromes, and acute myeloid l e~k e m i a .~.~ D e novo PNHh-' is an acquired clonal disorderY"" characterized by complement-mediated hemolysis and the expansion of affected cells of various hematopoietic lineages. The most typical manifestation of PNH is intravascular hemolysis due to abnormal sensitivity of red blood cells
[Hematology Reports 2012; 4:e17] [page 53]
2016
A case of pure red cell aplasia in a simultane-ous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unrespon-sive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of par-vovirus pure red cell aplasia, which was con-firmed with serology and polymerase chain reac-tion positive for parvovirus B19 DNA in periph-eral blood. After the administration of intra-venous immunoglobulin the anemia improved with a rising number of the reticulocytes.
Journal of Medical Case Reports, 2015
Introduction: Thrombotic microangiopathies are a group of diseases presenting as microangiopathic hemolytic anemia, thrombocytopenia and end-organ dysfunction. As the role of the complement system was elucidated in atypical hemolytic uremic syndrome pathogenesis, eculizumab was successfully introduced into clinical practice. We present a large pedigree with multiple individuals carrying a functionally significant novel factor H mutation. We describe the proband's presentation following a presumed infectious trigger requiring plasma exchange and hemodialysis. Case presentation: A 32-year-old Caucasian woman presented with pyrexia and headache lasting one week to our Emergency Department. She gave no history of diarrhea or other symptoms to account for her high temperature. She was not taking any medication. She was pyrexial (38°C), tachycardic (110bpm) and hypertensive (160/110mmHg). Her fundoscopy revealed grade IV hypertensive retinopathy. She had mild pretibial and periorbital edema, with oliguria (450mL/day). She had a pregnancy one year previously, during which she had hypertension, proteinuria and edema, with successful delivery at term. Her mother had died in her early 30s with a clinical picture consistent with thrombotic microangiopathy. Her laboratory evaluation showed microangiopathic hemolytic anemia. After 22 sessions of plasma exchange, her lactate dehydrogenase levels started to climb. As a result, she was classified as plasma resistant and eculizumab therapy was instituted. Her lactate dehydrogenase level and platelet count normalized, and her renal function recovered after three months of dialysis. Conclusions: We demonstrate that, even in patients with atypical hemolytic uremic syndrome and prolonged dialysis dependence, recovery of renal function can be seen with eculizumab treatment. We suggest a treatment regime of at least three months prior to evaluation of efficacy.
A complicated case of atypical hemolytic uremic syndrome with frequent relapses under eculizumab
Pediatric nephrology (Berlin, Germany), 2015
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9). We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses. Not every patient with aHUS...
Therapeutics and Clinical Risk Management, 2016
Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder resulting from somatic mutation in the PIG-A gene leading to a deficiency of the membraneanchoring molecule glycosylphosphatidylinositol. The lack of expression of two glycosylphosphatidylinositol-anchored proteins involved in the regulation of the complement system renders PNH erythrocytes susceptible to complement-mediated lysis. Clinical manifestations include thromboembolic disease, chronic kidney injury, pulmonary hypertension, smooth muscle dysfunction, and chronic hemolysis. Until recently, treatment was mainly supportive with most patients suffering from significant morbidity and shortened survival compared to age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has resulted in dramatic improvements of survival and reduction in complications. In this paper, we review some special considerations pertaining to the use of eculizumab for PNH.