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Bleeding Manifestations (bleeding + manifestation)
Selected AbstractsRecurrent idiopathic thrombocytopenic purpura in childhoodPEDIATRIC BLOOD & CANCER, Issue 2 2008Maria Vranou MD Abstract Background Idiopathic thrombocytopenic purpura (ITP) is a common haematological disease during childhood, that usually has a benign course; however, literature on the recurrent form of the disease (rITP) is limited. Procedure rITP was characterized by intermittent episodes of thrombocytopenia (TP) followed by periods of recovery, unrelated to therapeutic intervention. We retrospectively reviewed features of patients with rITP, diagnosed and systematically followed up at our center, during the period 1975,2004. Results Forty-eight of 795 children with ITP (6.0 %) presented with rITP. The majority of patients (68.8%) had only one recurrence, whereas only one patient had four. A time interval between two episodes longer than 3 months (up to 96) was identified in 2/3 of episodes and <3 months in 1/3. The initial episode and the first recurrence mostly shared features of acute ITP; however, 22.9% of the episodes appeared with a chronic self-limited course. Bleeding manifestations were rare (18.6% of episodes) and mild, and they tended to occur in severely thrombocytopenic patients, mainly at the onset of the initial episode; intracranial hemorrhage (ICH) occurred in a toddler with short duration thrombocytopenia. Intravenous , globulin (IVIG) or corticosteroids were administered in 24.5% of episodes. None of the patients needed splenectomy. Conclusion: rITP is a rare, mild, self-limited type of ITP, although ICH may occur in a profoundly TP child. Recurrence may occur close or far apart to a previous isolated TP episode. The duration of episodes varies considerably from patient to patient and from episode to episode in the same patient. The pathogenesis of rITP still remains unclear. Pediatr Blood Cancer 2008;51:261,264. © 2008 Wiley-Liss, Inc. [source] Danazol therapy in factor X deficiencyHAEMOPHILIA, Issue 5 2001S. Mukhopadhyay Factor X (FX) deficiency is a rare coagulation disorder that usually presents with bleeding manifestations and is treated with fresh frozen plasma or prothrombin complex concentrates. We report a case of FX deficiency in which the patient presented with bleeding as well as thrombosis. The patient responded to Danazol and relapsed when the drug was stopped. The occurrence of thrombosis in FX deficiency and the role of Danazol in coagulopathies are reviewed. [source] Role of RFLP using TspRI for carrier detection in Glanzmann's thrombasthenia: a report on two familiesINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p1 2010M. KANNAN Summary Glanzmann's thrombasthenia (GT) was diagnosed in two patients who presented with bleeding manifestations accompanied by absent platelet aggregation, secondary to adenosine-5'-diphosphate, adrenaline, arachidonic acid and collagen. Flow cytometry analysis for GPIIb/IIIa expression was done using CD61 and CD41 markers in these patients and their family members including siblings. The patients were sub typed as Type I as he had absent glycoproteins (GP) IIb/IIIa. Family studies by flow cytometry showed reduced GPII/IIIa expression in both the parents and one sibling. However, western blot showed abnormal GPIIb protein in all the family members including siblings. It is possible that abnormal GPIIb protein by western blot in family members may reflect their carrier status. Patients' DNA was analyzed for mutation in both the GPIIb and GPIIIa genes by conformational sensitive gel electrophoresis (CSGE), followed by sequencing. CSGE showed defect in exon 12 and the promoter region of GPIIb. By sequence, it was confirmed that both the mutations were homozygous one was c.1028T>C and the other one was M33320.1:g.951G>A. For one of these mutations, restriction fragment length polymorphism (RFLP) was developed to look for the same mutation in all the family members. RFLP was developed using a restriction enzyme (TspRI) against the patient's mutation, c.1028T>C in exon 12 of GPIIb gene. RFLP followed by gel electrophoresis revealed that the mutation was heterozygous in all the family members. The findings by RFLP were double confirmed by direct DNA sequencing of the exon 12 in all the family members. Thus, TspRI marker may be used as a RFLP marker to predict the carriers in GT families, if the patients' mutation status is identified. [source] Establishing an oral anticoagulant monitoring service in a multiethnic developing countryINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2008T. CASIMIRE Summary We describe the establishment of an International Normalized Ratio (INR)-based system for monitoring oral anticoagulant therapy in a multiethnic developing country. There was significant variation in geometric mean normal prothrombin time among ethnic groups: 12.7 s for Indians, 13.4 s for Africans and 13.7 s for subjects of mixed ancestry. About 4129 INR measurements were performed in the first 2 years. The majority (55.2%) of achieved INRs were subtherapeutic. We found 31 (0.8%) instances of severe overanticoagulation (INR > 8.0). There were no bleeding manifestations in 24 (77%) of them. Only two experienced life-threatening haemorrhage. The management of bleeding and excessive anticoagulation was not always in accordance with international recommendations. The high incidence of underanticoagulation in Trinidad and Tobago may be due to genetically determined warfarin resistance or underdosing. Oral anticoagulant monitoring in Trinidad and Tobago could benefit from the centralization of such services to designated clinics with specialized staff and computer-assisted dosing which adopt internationally accepted guidelines for practice. [source] Evaluation of low PAI-1 activity as a risk factor for hemorrhagic diathesisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2006A. ÅGREN Summary.,Background: Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking. Objective: To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population. Methods: In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA,PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age- and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls. Results: The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL,1, was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11,3.77 and 2.75; 1.39,5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22,8.56, P = 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA,PAI-1 was not associated with the increased bleeding tendency. Conclusion: Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations. [source] A novel Phe171Cys mutation in integrin ,IIb causes Glanzmann thrombasthenia by abrogating ,IIb,3 complex formationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2004N. Rosenberg Summary.,Background: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by lack of platelet aggregation induced by most agonists. The disease is caused by mutations in either ,IIb[glycoprotein (GP) IIb] or ,3 (GPIIIa) genes that lead to a lack or dysfunction of the integrin ,IIb,3 which serves as a fibrinogen receptor. Patients Mucocutaneous bleeding manifestations and platelet dysfunction consistent with GT were observed in three members of a Cypriot family: a 3-year-old proband, her father and her paternal uncle. Objective: To determine the molecular basis of GT in this family and to characterize possible biochemical and structural defects. Results: Analysis of the patients' platelets by fluorescence-activated cell sorting demonstrated trace amounts of ,3, no ,IIb and no ,IIb,3 on the membrane. Sequence analysis revealed a novel T607G transversion in exon 5 of the ,IIb gene predicting a Phe171Cys alteration that created a PstI recognition site. All three patients were homozygous for the mutation, the mother and paternal grandparents of the proband were heterozygous, whereas 110 healthy subjects lacked this transversion. Chinese hamster ovary cells cotransfected with cDNAs of mutated ,IIb and wild-type ,3 failed to express ,IIb,3 as shown by immunoprecipitation and immunohistochemistry experiments. Structural analysis of the ,IIb,3 model, which was based on the crystal structure of ,v,3, indicated that Phe171 plays an essential role in the interface between the ,-propeller domain of ,IIb and the ,A domain of ,3. Conclusions: A novel Phe171Cys mutation in the ,IIb gene of patients with GT is associated with abrogation of ,IIb,3 complex formation. [source] Rituximab-associated acute thrombocytopenia: An under-diagnosed phenomenon,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Ron Ram Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines,TNF-,, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Type I Glanzmann thrombasthenia: Most common subtypes in North IndiansAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2003M. Kannan Abstract The expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians. Glanzmann thrombasthenia was diagnosed in patients with bleeding manifestations accompanied by absent/reduced platelet aggregation, secondary to ADP, ADR, arachidonic acid, and collagen. Flow cytometry revealed variable GPIIb/IIIa expression by CD61 and CD41 in patients with Glanzmann thrombasthenia on the basis of CD61 levels, six patients were subtyped as type I because they had absent GPIIb/IIIa, three patients were subtyped as type II because their GPIIb/IIIa levels varied from 7.72% to 20.40%, and one patient was diagnosed as type III, because his clot retraction was 60% and GPIIb/IIIa was 46.0% of normal. Four fathers, three mothers, and five siblings were found to have GPIIb/IIIa levels less than 35% of normal. It is possible that low GPIIb/IIIa levels in family members may reflect their carrier status. It is postulated that flow cytometric estimation of GPIIb/IIIa in parents/siblings may detect carrier status in Glanzmann thrombasthenia. Am. J. Hematol. 74:139,141, 2003. © 2003 Wiley-Liss Inc. [source] | ||||||||||