Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hemoglobinuria”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2002

Relationship between aplastic anemia and paroxysmal nocturnal hemoglobinuria.

Since aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome was reported in 1967, the overlap of idiopathic aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) has been well known. The link between the 2 diseases became even more evident when immunosuppressive therapy improved survival of patients with severe AA. More than 10% of patients with AA develop clinically evident PNH. Moreover, flow cytometric analysis demonstrates that the majority of patients with AA have a subclinical percentage of granulocytes with PNH phenotype. Some of them have clearly recognizable PNH clones. Granulocytes with a PNH phenotype are also often found in normal individuals, though at much smaller percentages of cells. This finding suggests that a PNH clone is expanded in AA. consistent with a hypothesis that blood cells from patients with PNH are more resistant to an autoimmune environment. Survival of PNH clones in pathologic bone marrow may account for limited expansion of PNH clones; however, additional genetic change(s) that confers cells with growth phenotype may be required for the full development of PNH.

Anemia, Aplastic↗
PubMed2005

Cerebral ischemic infarction in paroxysmal nocturnal hemoglobinuria report of 2 cases and updated review of 7 previously published patients.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder, leading to a deficient biosynthesis of surface proteins in hematopoetic cells. Clinical symptoms consist of various combinations of intravascular hemolysis, bone marrow failure and mainly venous thrombotic events. Arterial thrombosis has been described only in a few cases. METHODS: We report two patients with fatal ischemic strokes in PNH caused by arterial occlusion. In addition we also reviewed 7 previously reported cases in the literature and obtained follow-up information on 4 of the 5 survivors. RESULTS: Both patients from our clinic had experienced hemoglobinuria and cytopenia prior to the vascular events but in one case diagnosis of PNH was only established after stroke onset. The causal role of PNH was supported by the absence of other vascular risk factors and by simultaneous symptoms of hemolysis and cytopenia. The diagnosis of PNH was confirmed by a positive result in flow cytometry. Despite extended therapeutic interventions, including antithrombotic treatment (with heparin or tirofiban) and decompressive hemicraniectomy both patients developed further thrombotic complications. The two patients died during their hospital stay from vascular or infectious complications. A review of all 9 published cases revealed that four patients died within a few weeks after the initial thrombotic event. No difference in treatment between patients with good or bad outcome was seen. CONCLUSIONS: PNH is a rare cause of arterial stroke but it should be considered in young stroke patients with abnormal blood findings. As yet, there is no effective antithrombotic treatment.

Adolescent↗
PubMed2004

Off-pump coronary artery bypass grafting in a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria has not been described in patients undergoing off-pump coronary artery bypass grafting. A 65-year-old man who underwent percutaneous coronary stenting to the proximal left anterior descending artery for unstable angina was readmitted to our hospital complaining of recurrent chest pains. A coronary angiography revealed in-stent restenosis and new lesions of the distal left anterior descending artery as well as the left circumflex artery branch. He was found to have paroxysmal nocturnal hemoglobinuria which contributes to serious surgical complications including infection, bleeding, hemolysis and acute renal failure. After pancytopenia was treated with administration of granulocyte colony stimulating factor and transfusion of the washed red blood cells preoperatively, off-pump coronary artery bypass grafting was performed. Cardiopulmonary bypass was avoided in order to reduce activation of complements. His postoperative course was uneventful. Combination of appropriate perioperative management and off-pump cardiac surgery yielded an effective result in treating this patient without major complications.

Aged↗
PubMed1975

Platelet hypersensitivity and intravascular coagulation in paroxysmal nocturnal hemoglobinuria.

The patient described had paroxysmal nocturnal hemoglobinuria associated with recurrent arterial as well as venous thrombosis. Study of platelet function revealed hypersensitivity to epinephrine, adenosine 5'phosphate (ADP) and collagen as judged by their ability to aggregate platelets as well as to release 14C serotonin. The release of total nucleotides was also markedly increased over normal with all aggregating agents. The abnormality was localized to the platelet since aggregation occurred when the patient's platelets were resuspended in normal plasma but not when normal platelets were incubated in the patient's plasma. Presumptive evidence for ongoing intravascular coagulation was an increase in fibrinogen derivatives of heavier molecular weight than the native protein presumably a result of thrombin action. However, factor XII was not activated and fibrinolysis was not increased. Complement component levels and antithrombin concentrations were also normal. The findings in this case suggest that hypersensitive platelets may contribute to the intravascular coagulation that is manifested by the increased incidence of thrombosis in patients with paroxysmal nocturnal hemoglobinuria.

Adenosine Diphosphate↗
PubMed1977

Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria.

A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate.

Acidosis, Renal Tubular↗
PubMed1980

Venous thrombosis and splenic rupture in paroxysmal nocturnal hemoglobinuria.

A patient with an 11 year history of paroxysmal nocturnal hemoglobinuria presented with severe abdominal pain. On admission, the hematocrit value was 30 per cent and unchanged from repeated measurements during the previous three years. Abdominal angiography identified extensive thromboses of the splenic and portal venous systems. After initial improvement on heparin therapy, the patient experienced additional abdominal crises. A ruptured and multifragmented spleen was removed at the time of exploratory laparotomy. Postoperatively, after a several days' interval of improvement, the patient experienced additional thrombotic episodes of the abdomen, upper extremities and cerebral cortex. The latter was associated with disabling nerve paralysis. With continuous intravenous heparin plus steroid therapy, the patient's condition improved progressively. Despite the numerous thrombotic episodes during the prolonged hospital course, no hemolytic episodes were observed. This is the first report of documented splenic rupture in a patient with paroxysmal nocturnal hemoglobinuria.

Adult↗
PubMed1993

Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized.

B-Lymphocytes↗
PubMed1987

Chromosomal subclonal evolution in paroxysmal nocturnal hemoglobinuria evolving into acute megakaryoblastic leukemia.

Four cytogenetic studies were performed in the course of a paroxysmal nocturnal hemoglobinuria evolving into acute megakaryoblastic leukemia. The clonal evolution was characterized by a unique structural change (9p) at the time of diagnosis, heralding an accelerated and complex karyotypic alteration including 5q-, 12p-, +21, -5, -7. At the terminal phase, the initial population was replaced within 1 week by a new overgrowing clone with -5, +8, +17. This suggests that the paroxysmal nocturnal hemoglobinuria-associated preleukemia and leukemic states share with acute nonlymphocytic leukemia the same nonrandom chromosomal changes.

Adult↗
PubMedDate not supplied

Paroxysmal nocturnal hemoglobinuria presenting as moyamoya syndrome.

We report an 11-year-old girl who has paroxysmal nocturnal hemoglobinuria (PNH) and was admitted because of recurrent cerebrovascular accidents (CVA) and intermittent hemoglobinuria. Internal carotid angiography revealed bilateral typical moyamoya patterns. Although CVA due to arterial thrombosis may occur in PNH, the basal moyamoya vessels were never mentioned in case reports yet. The moyamoya syndrome has been reported in a variety of diseases and represents the nonspecific response to an impairment of arterial flow at specific sites in the brain. Our case discloses that PNH may present as moyamoya syndrome.

Cerebral Angiography↗
PubMed1996

Bilateral papilledema with retinal hemorrhages in association with cerebral venous sinus thrombosis and paroxysmal nocturnal hemoglobinuria.

PURPOSE: To report a patient with paroxysmal nocturnal hemoglobinuria who complained of transient obscurations of vision and exhibited bilateral papilledema with retinal hemorrhages. METHODS: Case report. Computed tomography did not demonstrate any abnormality but magnetic resonance imaging disclosed signs of cerebral venous sinus thrombosis. RESULTS: The patient was treated with subcutaneous low molecular weight heparin and intravenous corticosteroids. Symptoms improved within one week and ophthalmoscopic signs resolved within four months. CONCLUSION: Bilateral papilledema with extensive retinal hemorrhages may be a sign of cerebral venous sinus thrombosis, a reported devastating complication of paroxysmal nocturnal hemoglobinuria. Thus, any patient with suspected cerebral venous sinus thrombosis should undergo magnetic resonance imaging, even when results of computed tomography are normal.

Anticoagulants↗
PubMed2003

Paroxysmal nocturnal hemoglobinuria in pregnancy.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which a defect of glycophosphatidylinositol (GPI)-anchored proteins in the cell membrane of bone marrow stem cells leads to increased sensitivity of the red cells to complement, causing intravascular hemolysis and hemoglobinuria. Other clinical features of this disease are cytopenia and an increased frequency of thrombotic events. We report a case of a pregnant woman with PNH on high-dosage anticoagulation therapy, the follow-up during the pregnancy, the delivery and the postpartum period. The obstetric literature on women with PNH is reviewed, the maternal and fetal risks are evaluated and the management of pregnancies and deliveries in such patients are discussed. During the pregnancy our patient was hypertransfused and used anticoagulation treatment. A healthy child was delivered in week 37 by cesarean section because of premature rupture of the membranes, unsuccessful induction and intrauterine infection. Because of bleeding problems a hysterectomy also had to be performed. In the postpartum period the patient developed her second episode of a liver vein thrombosis. She recovered gradually and 18 months after the delivery her disease is now in a stable phase. The literature shows a high maternal morbidity and mortality among pregnant PNH patients. Fetal wastage and prematurity rate are also high. Pregnancy in patients with PNH represents a high-risk situation for both the mother and the child and should not be recommended. A pregnant PNH woman should be followed closely by both obstetricians and hematologists.

Adult↗
PubMed2001

Paroxysmal nocturnal hemoglobinuria: insights from recent advances in molecular biology.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hemolytic anemia characterized by the increased sensitivity of red cells to complement, leading to intravascular hemolysis and hemoglobinuria. Other clinical features are cytopenias caused by bone marrow failure and an increased risk of thrombosis. If unrecognized and not treated appropriately, PNH is often associated with a substantial morbidity and mortality. PNH is caused by the expansion of a hematopoietic progenitor cell that caries a somatic mutation in the X-linked phosphatidylinositol glycan complementation group A (PIGA) gene. The PIGA gene encodes a protein essential in the biosynthesis of glycosylphosphatidylinositol (GPI)-anchor molecules. A proportion of blood cells from patients with PNH is therefore deficient in all GPI-linked surface proteins. Considerable progress in the field of PNH research in the last 7 years has resulted from the cloning of the PIGA gene. The purpose of the current article is to describe the structure and function of the PIGA gene, to summarize the lessons learned from the analysis of PIGA gene mutations, to review the impact of mouse models on our current understanding of the human disease, and to discuss the possible pathogenesis of PNH. In addition, we will outline novel approaches to PNH diagnosis, research, and therapy that became available thanks to the cloning of the PIGA gene.

Animals↗
PubMed1996

A knock-out model of paroxysmal nocturnal hemoglobinuria: Pig-a(-) hematopoiesis is reconstituted following intercellular transfer of GPI-anchored proteins.

We created a "knockout" embryonic stem cell via targeted disruption of the phosphatidylinositol glycan class A (Pig-a) gene, resulting in loss of expression of cell surface glycosyl phosphatidylinositol-anchored proteins and reproducing the mutant phenotype of the human disease paroxysmal nocturnal hemoglobinuria. Morphogenesis of Pig-a- embryoid bodies (EB) in vitro was grossly aberrant and, unlike EB derived from normal embryonic stem cells, Pig-A EB produced no secondary hematopoietic colonies. Chimeric EB composed of control plus Pig-A- cells, however, appeared normal, and hematopoiesis from knock-out cells was reconstituted. Transfer in situ of glycosyl phosphatidylinositol-anchored proteins from normal to knock-out cells was demonstrated by two-color fluorescent analysis, suggesting a possible mechanism for these functional effects. Hematopoietic cells with mutated PIG-A genes in humans with paroxysmal nocturnal hemoglobinuria may be subject to comparable pathophysiologic processes and amenable to similar therapeutic protein transfer.

Animals↗
PubMed2003

Hemoglobinuria with ribavirin treatment.

Chronic hepatitis C virus is a major worldwide cause of hepatitis, cirrhosis, end-stage liver disease, and hepatocellular carcinomas. Combination therapy of ribavirin with short- or long-acting interferon-alpha is now the standard treatment of chronic hepatitis C. This therapy is associated with a wide range of side effects. Although hemolysis is almost an invariable result of ribavirin, black urine due to hemoglobinuria has never been previously reported. We recently encountered two cases of black urine (hemoglobinuria) in patients treated with combination therapy. Based on reports of dark urine in many of our patients, we suggest that this phenomenon may be more common than is currently appreciated. It indicates a marked degree of hemolysis, which prompts immediate measurement of hemoglobin level.

Adult↗
PubMed2001

New insights into paroxysmal nocturnal hemoglobinuria.

The characteristic, defining defect in paroxysmal nocturnal hemoglobinuria is the somatic mutation of the PIG-A gene (essential to the biosynthesis of the glycosylphosphatidylinositol moiety that affixes a number of proteins to the cellular surface) in hematopoietic cells. These cells thus lack the proteins usually held in place by this anchor. The absence of these proteins is the most reliable diagnostic criterion of the disease and is responsible for many of the clinical manifestations of PNH. The current hypothesis explaining the disorder suggests that there are two components: (1) hematopoietic stem cells with the characteristic defect are present in the marrow of many if not all normal individuals in very small numbers; (2) some aplastogenic influence suppresses the normal stem cells but does not suppress the defective stem cells, thus allowing the proportion of these cells to increase. Current research attempts to substantiate this hypothesis and design therapy consistent with the hypothesis. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by intravascular hemolysis, hypercoagulability, and relative bone marrow failure [1]. It is characterized by a somatic mutation in the gene encoding the alpha1-6-N-acetylglucosaminyltransferase necessary for the formation of the glycosylphosphatidylinositol (GPI) anchor that binds certain proteins to the membrane surface (Fig. 1) [2,3*]. Whereas many of the manifestations can be accounted for by the absence of these proteins on the cells of the hematopoietic system, it is not entirely clear whether this defect is sufficient to make the disease manifest. In this paper, the author reviews recent clinical observations and relates them to the underlying pathophysiology of the disease.

Animals↗
PubMed2004

Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan.

: To determine and directly compare the clinical course of white and Asian patients with paroxysmal nocturnal hemoglobinuria (PNH), data were collected for epidemiologic analysis on 176 patients from Duke University and 209 patients from Japan. White patients were younger with significantly more classical symptoms of PNH including thrombosis, hemoglobinuria, and infection, while Asian patients were older with more marrow aplasia. The mean fraction of CD59-negative polymorphonuclear cells (PMN) at initial analysis was higher among Duke patients than Japanese patients. In both cohorts, however, a larger PNH clone was associated with classical PNH symptoms, while a smaller PNH clone was associated with marrow aplasia. Thrombosis was significantly more prevalent in white patients than Asian patients, and was associated with a significantly higher proportion of CD59-negative PMN. For individual patients, CD59-negative populations varied considerably over time, but a decreasing PNH clone portended hematopoietic failure. Survival analysis revealed a similar death rate in each group, although causes of death were different and significantly more Duke patients died from thrombosis. Japanese patients had a longer mean survival time (32.1 yr vs. 19.4 yr), although Kaplan-Meier survival curves were not significantly different. Poor survival in both groups was associated with age over 50 years, severe leukopenia/neutropenia at diagnosis, and severe infection as a complication; additionally, thrombosis at diagnosis or follow-up for Duke patients and renal failure for Japanese patients were poor prognostic factors. These data identify important differences between white and Asian patients with PNH. Identification of prognostic factors will help the design of prospective clinical trials for PNH.

Adolescent↗
PubMed2006

Clinical management of paroxysmal nocturnal hemoglobinuria in pregnancy: a case report and updated review.

UNLABELLED: Because women with paroxysmal nocturnal hemoglobinuria (PNH) are especially vulnerable to thromboembolic phenomena, pregnancy is a time of increased risk for both mother and fetus. However, pregnancies in affected women are rare; only case reports and small studies have been reported so far. We present the case of a 20-year-old woman with PNH who, while undergoing medical tests in preparation for a bone marrow transplant, was discovered to be pregnant. We also review the obstetric literature on pregnancy complicated by PNH, which indicates that both maternal and fetal mortality is exceptionally high (11.6% and 7.2%) with the major cause of maternal mortality being thromboembolism. Major maternal complications are more frequent postpartum (30.2%) than antepartum or intrapartum (16.3%). TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that paroxysmal nocturnal hemoglobinuria (PNH) during pregnancy increases adverse events for both the mother and the fetus, state that maternal and fetal mortality are both high, and explain that the major complications occur in the postpartum period.

Adult↗