Case Of Paroxysmal Nocturnal Hemoglobinuria Research Articles

Flow Cytometry Screening for Paroxysmal Nocturnal Hemoglobinuria Abnormal Clones in Saudi Arabia

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease with insidious process, chronic course and life-threatening condition. PNH is clinically defined by the deficiency of the endogenous glycosyl phosphatidylinositol (GPI)-anchored complement inhibitory protein. It has always aroused interest in the medical profession rendering screening and proper diagnosis by flow cytometry (FCM) technology a priorityWe reviewed all samples submitted for PNH/ FCM screening for the past 2 years (2012-2013) at hematology section, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center (General Organization). We collected the positive cases and reviewed them for age, gender, indication for screening, sample type, size of the PNH clone and cell type affected. Immunophenotypic analysis was performed using gating antibodies CD45, CD15, CD33, CD235a GPI-linked antibodies, CD59, CD14, and CD24 as well as fluorescent Aerolysin (FLAER).In a total of 366 peripheral blood samples submitted for PNH/ FCM screening fifteen samples (4%) were positive for PNH clones but only 12 patients were available for analysis. The median age for our patients was 34 years with approximately equal male to female distribution.12 cases showed type II and III clones within the RBCs with clone size ranging between 0.04% and 56%. Analysis of granulocytes and monocytes revealed type III clone in 8 cases, type II and III clone in 3 cases and non in one case. The percentage of the clone varies between the granulocytes and monocytes and ranges from 1% up to 100%.Of 12 positive PNH cases, 8 (66.7%) patients were diagnosed as having aplastic anemia (AA), 1 (8.3%) patient with Budd-Chiari syndrome, 1 (8.3%) patient has chronic immune thrombocytopenia (ITP), and 2 (16.7%) patients presented with pancytopenia.This study confirms the rarity of the disease since only 4% of the submitted samples for analysis turned to be positive for PNH. The detection limit for a PNH clone by FCM in the RBC or WBC is 0.01%. Identification of small PNH clone is greater FCM sensitivity relative to old test used for the same purpose (Ham test). The use of the FLAER allowed us to detect granulocytic PNH clone, however, granulocytes PNH clone detection alone without RBCs clone detection is not recommended. This review confirms the previous percentage of positive cases (5.9%) reported from this center on a smaller number of cases during the past few years. DisclosuresNo relevant conflicts of interest to declare.

Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-.

We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A- ( G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in the PIGA gene. PIGA encodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol ( GPI) anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been selected because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking co-trimoxazole, a drug that precipitates hemolysis in G6PD deficient individuals. Since both G6PD and PIGA are X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normal G6PD B allele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode.

Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-

We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A- ( G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in the PIGA gene. PIGA encodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol ( GPI) anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking Bactrim, a drug that precipitates hemolysis in G6PD deficient individuals. Since both G6PD and PIGA are X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normal G6PD B allele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode.

Paroxysmal Nocturnal Hemoglobinuria and Magnetic Resonance Imaging

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and complex disease characterized by a severe prothrombotic state caused by a complement system mediated hemolysis. The introduction of the anti-C5 antibody, Eculizumab, has been conducted in many Hematology units worldwide to adopt new diagnostic tools to evaluate new and old PNH patients in order to consider the adequacy of the adoption of this new drug in each case.Magnetic Resonance Imaging (MRI) allows a more adequate and profitable approach in PNH that other radiology techniques used for this purpose. In the last four years Hematology and Radiology units in our Hospital have collaborate in the clinical evaluation of PNH patients performing MRI (cranioencephalic, thoracic and/or abdominal) in acute complications of PNH patients (9 patients) or as a programmed protocoled evaluation previous to consider Eculizumab treatment (14 patients).The protocoled evaluation consists in thoracic and abdominal MRI evaluations in all cases, and cranioencephalic MRI (with independence of the presence of neurological symptoms) in 9 cases. The PNH patients were examined with 1.5 Teslas magnet for cranioencephalic,thoracic and abdominal MRI and with 3.0 Teslas magnet for some cranioencephalic MRI (Achieva Magnets; Philips Healthcare, Best, The Netherlands).Different protocols designed for the study of this pathology, using morphological sequences with different empowerment, functional sequences and angiographic studies after administration of intravenous contrast (gadobutrol) have been used. In the abdominal explorations had been performed calculations of T2 * for the quantification of deposit of iron in liver and kidney.The first group of patients (incidental studies in acute/chronic situations) included Classical and with other bone marrow failure syndrome (BMFS) Parker's types. The second group (protocoled studies previous consideration of Eculizumab therapy) consisted on 11 Classical Parker's type patients with active hemolysis (LDH increased 3-13 times over normal levels) and elevated PNH clone (73-99% negative GPI granulocytes by FLAER cytometry); and 3 with BMFS Parker's type patients (LDH increased 2-6 times over normal levels) with lower PNH clone (43-50% negative GPI granulocytes by FLAER cytometry). Thrombosis was found in four cases, one in the inferior cava and and three arterial (two cerebral and one in descendent aorta). In three patients this finding implied to initiate Eculizumab therapy. Minor ischemic brain changes were displayed by three patients. None of the eighteen patients explored with thoracic MRI, displayed pulmonary hypertension signs despite the elevation of pro-BNP in eight of them. Iron overload in the liver and/or kidneys were very frequent. The finding of a reversal of the normal cortical and medullary intensities on T1 and T2 weighted images of both kidneys was evident in the majority of patients with severe PNH types. Interestingly, one patient with a chronic PNH severe form displayed no renal iron cortical after two years on Eculizumab therapy. This finding was also evident in patients with active hemolysis in the past but with very low PNH clones and clinical remission of the disease.Many other incidental discoveries includes cholelithiasis, splenomegaly, kidney arterial vessel constriction, vascular anomalies, kidney and vesical stones, adrenal adenoma, atheromatosis at different levels, Tornwaldt cyst, hamartoma, hemangiomas and abnormal bone marrow signal.MRI is the best imaging technique to diagnose thrombosis in PNH patients and to control evolution. Moreover, in the cerebrovascular setting allows a more fine and precise diagnosis of the minor pathologic thrombotic changes. MRI is the only imaging technique that permits to evaluate the iron overload that in some PNH cases could be underestimated and needs quelation therapy. In our opinion all new patients with classical severe hemolytic PNH must be evaluated prospectively with MRI. The collaboration of the Radiology team with the Hematologist is fundamental to acquire expertise in this rare disease. Disclosures:Pastrana:Alexion Pharmaceuticals: Speakers Bureau. Ojeda:Alexion Pharmaceuticals: Consultancy, Speakers Bureau.

A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT

AbstractTo ascertain the genetic basis of a paroxysmal nocturnal hemoglobinuria (PNH) case without somatic mutations in PIGA, we performed deep next-generation sequencing on all exons of known genes of the glycosylphosphatidylinositol (GPI) anchor synthesis pathway. We identified a heterozygous germline splice site mutation in PIGT and a somatic 8-MB deletion in granulocytes affecting the other copy of PIGT. PIGA is essential for GPI anchor synthesis, whereas PIGT is essential for attachment of the preassembled GPI anchor to proteins. Although a single mutation event in the X-chromosomal gene PIGA is known to cause GPI-anchored protein deficiency, 2 such hits are required in the autosomal gene PIGT. Our data indicate that PNH can occur even in the presence of fully assembled GPI if its transfer to proteins is defective in hematopoietic stem cells.

Occupancy of whole blood cells by a single PIGA‐mutant clone with HMGA2 amplification in a paroxysmal nocturnal haemoglobinuria patient having blood cells with NKG2D ligands

Occupancy of whole blood cells by a single <i><scp>PIGA</scp></i>‐mutant clone with <i><scp>HMGA</scp>2</i> amplification in a paroxysmal nocturnal haemoglobinuria patient having blood cells with <scp>NKG</scp>2D ligands

Infarctus rénal veineux, une complication de l’hémoglobinurie paroxystique nocturne

Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease) is a rare acquired clonal disorder of the hematopoietic cell, to a somatic mutation in the phosphatidylinositol glycan (PIG-A). The most frequent clinical manifestations are hemolytic crisis and venous thrombosis of the mesenteric, hepatic, portal or cerebral territories. We report a case of paroxysmal nocturnal hemoglobinuria with renal vein thrombosis, a rare complication of this disease.

Clinical features and prognostic factors of Asian patients with paroxysmal nocturnal hemoglobinuria: results from a single center in China

Although all patients with paroxysmal nocturnal hemoglobinuria (PNH) have acquired mutations in the phosphatidylinositol glycan class-A(PIG-A)gene, their clinical courses are highly variable. We reviewed 280 PNH cases referred to our hospital from January 1990 through June 2010 to assess clinical presentations, prognostic factors influencing survival, difference among subcategories, and clinical significance of PNH clone size. The overall survival at 10years after diagnosis estimated by Kaplan-Meier was 77.6%. Both univariate and multivariate analyses identified risk factors affecting survival, including age >40years, absolute neutrophil count<0.5 × 10(9) cells/L, development of thrombotic events, evolution to myelodysplastic syndrome or acute myelogenous leukemia, and recurrent infections. The cohort of patients were divided into subcategories of classic PNH, PNH/AA, and PNH-sc/AA based on the recent proposed PNH working clinical classification, hemoglobinuria as the initial symptomatic manifestation was high up to 82.0% in classic PNH subcategory, whereas only as low as 1.4% in PNH-sc/AA subcategory; the frequencies of infectious (26.0%) and bleeding symptoms (14.0%) in classic PNH subcategory were significantly less than those in PNH/AA (25.3% and 51.7%, respectively) and PNH-sc/AA (48.3% and 83.2%, respectively) subcategories. Our results revealed that large PNH clone was associated with increased risks for hemoglobinuria and thrombosis, whereas small PNH clone was associated with bone marrow failure. Thus, this study may shed insights into Chinese PNH patients to set up individually therapeutic regimens.

Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report

IntroductionParoxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis.Case presentationA 29-year-old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV). She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria.ConclusionsTo the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases.

3′UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice

AbstractOverexpression of high mobility group AT-hook 2 (HMGA2) is found in a number of benign and malignant tumors, including the clonal PIGA− cells in 2 cases of paroxysmal nocturnal hemoglobinuria (PNH) and some myeloproliferative neoplasms (MPNs), and recently in hematopoietic cell clones resulting from gene therapy procedures. In nearly all these cases overexpression is because of deletions or translocations that remove the 3′ untranslated region (UTR) which contains binding sites for the regulatory micro RNA let-7. We were therefore interested in the effect of HMGA2 overexpression in hematopoietic tissues in transgenic mice (ΔHmga2 mice) carrying a 3′UTR-truncated Hmga2 cDNA. ΔHmga2 mice expressed increased levels of HMGA2 protein in various tissues including hematopoietic cells and showed proliferative hematopoiesis with increased numbers in all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis and erythropoietin-independent erythroid colony formation. ΔHmga2-derived BM cells had a growth advantage over wild-type cells in competitive repopulation and serial transplantation experiments. Thus overexpression of HMGA2 leads to proliferative hematopoiesis with clonal expansion at the stem cell and progenitor levels and may account for the clonal expansion in PNH and MPNs and in gene therapy patients after vector insertion disrupts the HMGA2 locus.

Erythrocyte membrane defects and asymmetry in paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome

Paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndromes (MDS) are clonal disorder of haematopoietic stem cells that may eventually lead to chronic anemia. The ultrastructural defects in erythrocyte membranes may have a role in early red cell destruction within circulation. The lifespan of the erythrocyte primarily correlates to externalization of phosphatidylserine (PS) and loss of glycophorins from the erythrocyte surface. The span of survival of mature erythrocytes in the circulation in case of MDS and PNH is yet unclear and has been studied by measuring simultaneous exposure of PS and loss of glycoconjugates, primarily glycophorins from membrane surface. The extent of the loss of PS asymmetry and cell surface glycophorins in density separated erythrocytes of six MDS and three PNH patients has been probed by fluorochrome conjugated annexin V and wheat germ agglutinin using flow cytometry. The cells with lighter density showed a higher amount of PS on the outer surface compared to those of heavier cells in all PNH and MDS cases, showing the opposite trend to that observed in normal erythrocytes. In addition, the lighter cells had more cell surface glycophorins compared to heaver cells in all the cases. Such lowering of glycophorin levels from the lighter to heavier cells was maximum in refractory anaemia (RA) and minimum in the normal cells studied. Greater loss of PS asymmetry and cell surface glycophorin in the lighter or younger erythrocytes together could be responsible for their faster destruction and removal (eryptosis) in PNH and MDS.

Primary/De Novo Paroxysmal Nocturnal Hemoglobinuria in a Child From North India

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder, characterized by intravascular hemolysis, thrombosis, or bone marrow failure. It is very rare in children. The clinical manifestations are due to deficiency of a family of membrane proteins that are anchored into the cell membrane through glycosylphosphatidylinositol (GPI). Currently, flow cytometric analysis of GPI-linked proteins has replaced the traditional Ham test (acidified-serum lysis test) and sucrose lysis test, it being a quantitative and more sensitive method. The only curative treatment of the disease is stem cell transplantation. We are reporting a case of de novo pediatric PNH, presenting with hemoglobinuria and a sizeable clone of GPI-anchor deficient blood cells, along with review of reported cases of PNH in pediatric patients. PNH can occur in children and has varied clinical and hematologic presentations; the presence of PNH should be considered in every child with an acquired bone marrow failure, unexplained hemoglobinuria and/or unexpected serious thrombosis. Pediatricians should keep this disorder in mind, when patients present with above features.

Screening for Paroxysmal Nocturnal Hemoglobinuria (PNH) in Patients with Cytopenia and Suspected Myelodysplasia Using the Fluorochrome-Conjugated Derivative of Aerolysin, FLAER

Evaluation of patients with peripheral blood cytopenias includes bone marrow assessment by cytomorphology and cytogenetics for findings suggestive of a myelodysplastic syndrome (MDS) or proving this diagnosis. While multiparameter flow cytometry (MFC) may increasingly add diagnostic information regarding MDS, MFC is the essential method for the assessment of an important differential diagnosis, paroxysmal nocturnal hemoglobinuria (PNH). Furthermore, it has been suggested by the International PNH Interest Group to screen patients with MDS once yearly for the presence of PNH clones irrespective of the occurrence of hemolysis. While the flow cytometric analysis for PNH has been based for decades on the detection of GPI-anchored surface antigens the methodological spectrum has been broadened recently by the introduction of FLAER (Protox Biotech, Victoria, BC) which is a fluorochrome-conjugated, mutated and inactivated derivative of the bacterial toxin, aerolysin. It directly binds to the GPI moiety of GPI-linked structures and has been shown to reproducibly detect even small amounts of cells from PNH clones at less than 1%. In order to assess the diagnostic value of FLAER in screening patients with cytopenia and suspected MDS for PNH we applied FLAER in parallel to the standard evaluation for PNH as well as for MDS. Of 29 patients analyzed 10 were diagnosed by cytomorpholgy as having MDS, 5 as possible MDS, 2 as chronic myelomonocytic leukemia, 4 as acute myeloid leukemia (AML), 5 as reactive conditions, 1 as aplastic anemia, 1 as toxic cytopenia following chemotherapy, and 1 was not evaluable. The evaluation for PNH included the assessment of CD55 and CD59 on erythrocytes, granulocytes and monocytes as well as of CD16 on granulocytes and of CD14 on monocytes. In addition, FLAER was used to analyze granulocytes and monocytes. In three PNH cases analyzed as controls both conventional markers as well as FLAER clearly demonstrated the affected populations. While the assessment of CD55, CD59, CD16, and CD14 did not reveal a sign suggestive of PNH in any of the 29 patients there were 7 patients in whom a reduced signal for FLAER was found in a portion of the granulocytes. This portion ranged from 10% to 29% of all granulocytes. Similar findings, although less striking, were obtained in monocytes. Interestingly, all of these 7 cases, with the exception of the case not evaluable by cytomorphology, had a diagnosis of either MDS or AML (aberrant karyotype in 4/7) and no aberrant signal for FLAER was found in patients with non-malignant diagnoses. These data suggest that by applying FLAER GPI-deficient cells and thereby PNH-clones may be detected in patients with MDS and AML. It remains to be proven, however, which diagnostic significance is carried by FLAER in the absence of findings by conventional markers suggestive of PNH. Further studies are warranted to assess the clinical utility of adding FLAER to the standard diagnostic panel for PNH, particularly in the setting of patients diagnosed with MDS.

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

A Case of Paroxysmal Nocturnal Hemoglobinuria with DIC after Laparoscopic Appendectomy

A Case of Paroxysmal Nocturnal Hemoglobinuria with DIC after Laparoscopic Appendectomy

Paroxysmal Nocturnal Hemoglobinuria in Children

Paroxysmal nocturnal hemoglobinuria (PNH), an acquired hematologic disorder characterized by intravascular hemolysis, nocturnal hemoglobinuria, thrombotic events, serious infections, and bone marrow failure, is very rare in children. PNH is caused by a somatic mutation of the phosphatidylinositol glycan (GPI) complementation class A (PIGA) gene, followed by a survival advantage of the PNH clone, which results in a deficiency of GPI-anchored proteins on hematopoietic cells. Currently, immunophenotypic GPI-linked anchor protein analysis has replaced the acid Ham and sucrose lysis test, as it provides a reliable diagnostic tool for this disease. The presence of PNH clones should be considered in every child with an acquired bone marrow failure syndrome, for example (hypoplastic) myelodysplastic syndrome and aplastic anemia, and/or unexpected serious thrombosis. Treatment of PNH in children is dependent on the clinical presentation. In cases of severe bone marrow failure, stem cell transplantation should be seriously considered as a therapeutic option even if no matched sibling donor is available. This article reviews the reported cases of PNH in children using the recently published guidelines for classification, diagnostics, and treatment.

The Incidence and Prevalence of Paroxysmal Nocturnal Hemoglobinuria (PNH) and Survival of Patients in Yorkshire.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder characterized by the expansion of a population of blood cells deficient in glycosylphosphatidylinositol (GPI) linked proteins. This results in the classical clinical features of intravascular hemolysis and thrombosis. PNH is known to be a rare disorder, but its incidence and prevalence have so far been poorly defined with very few studies. In order to better define the incidence and prevalence of PNH, survival data was collected on all patients diagnosed with PNH in the strategic health authorities of North and East Yorkshire, Northern Lincolnshire and West Yorkshire between January 1991 and July 2006. All patients were diagnosed by flow cytometry for GPI-linked antigens on red cells and neutrophils at a single reference laboratory (HMDS). The population of the study region is 3,742,835 (based on the 2001 census of Britain). 76 PNH patients were diagnosed during this time period giving an incidence of 0.13/100,000/year. Based on incidence and survival rates, the estimated 15 year prevalence of PNH is 1.59 per 100,000 resulting in a predicted prevalence of 59 patients in the study region. We have previously demonstrated that a neutrophil clone size >50% is a predictor of increased thrombotic risk; the current study predicts that 25% of patients will have >50% PNH neutrophil clone size, 43% with >10%, and 82% with >1%. Platelet count >100 x 109/L has been used as a criteria to consider primary prophylactic anticoagulation in PNH patients with substantial hemolysis if the neutrophil clone size is >50%. In the current study, the platelet count is >100 x 109/L in 32% of patients and <30 x 109/L in 27%. The primary clinical manifestation of PNH is intravascular hemolysis and although levels of hemolysis vary considerably between patients even those with relatively small PNH clones will have some degree of hemolysis. Levels of LDH (a sensitive marker of hemolysis) were elevated above the upper limit of the normal range in 82.5% of patients. Of the 59 patients in the study region, 33% reported hemoglobinuria. Overall survival was 78% with a median follow-up of 6.25 years (range 0 to 15 years). Survival was compared between patients with a) hemoglobinuria (89%) vs. those without (76%); b) neutrophil clone size ≥50% (81%) vs. <50% (80%) and c) Platelet counts <30 x 109/L (61%) vs. ≥30 x 109/L (86%) by univariate analysis. Hazard ratios and 95% confidence intervals were estimated using Cox's proportional hazards model adjusted for age and sex. Worse survival was only significantly predicted by a platelet count <30 x 109/L (log rank test, p=0.008). With a population of 57,105,375 (2001 census of Britain), Great Britain should have an estimated 75 new cases of PNH per year and a predicted prevalence of 908 patients. The U.S.A. will therefore have 4713 cases of PNH based on its July 1, 2005 census bureau population estimate of 296,410,404. This study is the first to accurately report the incidence and prevalence of PNH in a given population in a well-defined geographical area.

Neutropenia due to Parvovirus B19 Infections in Patients with Paroxysmal Nocturnal Hemoglobinuria

Two patients with paroxysmal nocturnal hemoglobinuria (PNH) and parvovirus B19 (PVB19) infection are reported. One was infected by PVB19-contaminated blood transfusion, whereas the other had become infected naturally. Both patients completely recovered after transient pancytopenia, but showed severe and intermediate neutropenia (0.216 and 0.768 × 10⁹/l, respectively) at the nadirs of aplastic crises. In the literature, PNH cases also showed neutropenia (0 and 0.54 × 10⁹/l) at aplastic crises. When patients with PNH are infected by PVB19, they may show severe neutropenia and mild thrombocytopenia in addition to severe reticulocytopenia. Therefore, these patients might have to be treated with granulocyte colony-stimulating factor to be able to recover from severe neutropenia.

Paroxysmal Nocturnal Hemoglobinuria Superimposed with Preeclampsia

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by complement-mediated intravascular hemolysis. As maternal complication of PNH is already severe, it becomes much more complex when preeclampsia is superimposed. We present a case of PNH superimposed with severe preeclampsia in the third trimester. A 30-year-old, gravida 1, para 0, woman had PNH, diagnosed at the age of 17. Her PNH was stable under medication. In 2004, she conceived and had prenatal care at our hospital. At 35 weeks of gestation, preeclampsia with elevated blood pressure and proteinuria were superimposed and managed with close surveillance. A live male baby was delivered vaginally at 38 weeks of gestation. During parturition, her blood pressure increased to 180/100 mmHg. Thrombocytopenia, hyponatremia, hyperkalemia, hypoalbuminemia, elevated liver enzymes and lactate dehydrogenase were also noted. Preeclampsia continued to postpartum and eventually disappeared. The most frequent causes of PNH-related fetomaternal morbidity and mortality are hemolysis and thrombosis. The situation becomes even more complicated when PNH is superimposed with preeclampsia. Appropriate clinical surveillance, awareness of the potential risks of hemolysis and thrombosis, as well as evaluation of fetal wellbeing are essential.

A case of paroxysmal nocturnal hemoglobinuria complicated with IgA nephropathy who developed acute renal failure induced by hemolytic crisis

A case of paroxysmal nocturnal hemoglobinuria complicated with IgA nephropathy who developed acute renal failure induced by hemolytic crisis