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Bleeding Phenotype (bleeding + phenotype)
Selected AbstractsVariability in bleeding phenotype in Amish carriers of haemophilia B with the 31008 C,T mutationHAEMOPHILIA, Issue 1 2009A. SHARATHKUMAR Summary., The aim of this study was to characterize the variability of bleeding phenotype and its association with plasma factor IX coagulant activity (FIX:C) in haemophilia B carriers in a large Amish pedigree with a unifying genetic mutation, C-to-T transition at base 31008 of the factor IX gene (Xq27.1,27.2). A cross-sectional survey of haemophilia B carriers included a multiple choice questionnaire evaluating symptoms of mucocutaneous bleeding, joint bleeding and bleeding after haemostatic stress [menstruation, postpartum haemorrhage (PPH), dental extractions and invasive surgeries]. Severity of bleeding was graded as 0 to 4, 0 being no bleeding whereas 4 being severe bleeding. Association between total bleeding scores and the FIX:C was evaluated. Sixty-four haemophilia B carriers participated in this study. Median age: 18 years (range 1,70 years); median bleeding score: 1 (range 0,8). Besides PPH, isolated symptoms of bruising, epistaxis, menorrhagia and postsurgical bleeding including dental extraction were not associated with lower FIX:C. Bleeding score ,3 was associated with involvement of at least two bleeding sites and a lower mean FIX:C of 42 ± 10.3% (95% CI 36.4,47.7) while a score >3 had involvement of ,2 sites and higher mean FIX:C of 54.9 ± 21.5% (95% CI 49,61), P = 0.005. Subcutaneous haematoma formation and bleeding after haemostatic stress requiring treatment were associated with bleeding scores ,3. Phenotypic variability existed among the carriers of haemophilia B who belonged to a single pedigree carrying a single unifying mutation. The utility of bleeding scores to define bleeding phenotype precisely in haemophilia B carriers needs further evaluation. [source] Health-related quality of life among adult patients with moderate and severe von Willebrand diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2010E. M. DE WEE Summary.,Background:,von Willebrand Disease (VWD) is the most frequent inherited bleeding disorder. It is unknown how this disorder affects quality of life. Objectives:,This nationwide multicenter cross-sectional study determined health-related quality of life (HR-QoL) in adult patients with moderate or severe VWD, and assessed whether bleeding severity and type of VWD are associated with HR-QoL. Methods:,HR-QoL was assessed using the Short Form (SF)-36, and bleeding severity was measured using the Bleeding Score (BS). Results:,Five hundred and nine patients participated; 192 males and 317 females, median age and range 45 (16,87) and 47 (16,84) years, respectively. Compared with the general population, HR-QoL in VWD patients was lower in the vitality domain (61 vs. 66 P < 0.001 for females, 67 vs. 72 P < 0.001 for males). Patients with the most severe bleeding phenotype (highest quartile BS, BS > 17) had a lower HR-QoL in eight domains than patients with a less severe bleeding type (lowest quartile BS, BS < 7) in the univariate analysis. After adjustment for age, gender, co-morbidity and employment/educational status, a more severe bleeding phenotype was associated with lower scores on the domains of physical functioning, role limitations due to physical functioning, bodily pain, general health, social functioning and physical component summary. Conclusions:,HR-QoL is lower in VWD patients compared with the general population. HR-QoL is strongly associated with bleeding phenotype. [source] Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profileJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2010E. SANTAGOSTINO Summary.,Background: Patients with severe hemophilia may show very varied bleeding tendencies, and the reasons for this heterogeneous clinical expression are unclear. The factor VIII/FIX genotype is the main determinant of the residual factor activity; however, different bleeding phenotypes have also been reported in patients sharing the same mutation. Such global coagulation tests as thrombin generation assays are tools with which to investigate different coagulation profiles among severe hemophiliacs. Objectives, patients and methods: This case,control study was aimed at comprehensively evaluating the role of genotype and endogenous thrombin potential (ETP) as predictors of the clinical phenotype in severe hemophiliacs with an extremely mild bleeding tendency (cases, n = 22), in comparison with those showing a typical bleeding tendency (controls, n = 50). Results: Cases were more frequently affected by hemophilia B than by hemophilia A, and showed a lower incidence of severe FVIII/FIX gene defects (referred to as null mutations), higher FVIII and FIX antigen levels and higher ETP values in platelet-rich plasma than controls (P < 0.05). By multivariate logistic regression, only non-null mutations were confirmed as an independent predictor of a mild clinical phenotype. Conclusions: These results indicate that non-null mutations represent the main determinant of the bleeding tendency, and that ETP measurement in platelet-rich plasma is able to identify severe hemophiliacs with a mild clinical phenotype. [source] Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpuraJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2008E. E. GARDINER Summary.,Background:,Receptors on platelets that contain immunoreceptor tyrosine-based activation motifs (ITAMs) include collagen receptor glycoprotein (GP) VI, and Fc,RIIa, a low affinity receptor for immunoglobulin (Ig) G. Objectives:,We examined the function of GPVI and Fc,RIIa in a patient diagnosed with immune thrombocytopenic purpura (ITP) who had unexplained pathological bruising despite normalization of the platelet count with treatment. Methods and Results:,Patient platelets aggregated normally in response to ADP, arachadonic acid and epinephrine, but not to GPVI agonists, collagen or collagen-related peptide, or to Fc,RII-activating monoclonal antibody (mAb) 8.26, suggesting ITAM receptor dysfunction. Plasma contained an anti-GPVI antibody by MAIPA and aggregated normal platelets. Aggregating activity was partially (,60%) blocked by Fc,RIIa-blocking antibody, IV.3, and completely blocked by soluble GPVI ectodomain. Full-length GPVI on the patient platelet surface was reduced to ,10% of normal levels, and a ,10-kDa GPVI cytoplasmic tail remnant and cleaved Fc,RIIa were detectable by western blot, indicating platelet receptor proteolysis. Plasma from the patient contained ,150 ng mL,1 soluble GPVI by ELISA (normal plasma, ,15 ng mL,1) and IgG purified from patient plasma caused Fc,RIIa-mediated, EDTA-sensitive cleavage of both GPVI and Fc,RIIa on normal platelets. Conclusions:,In ITP patients, platelet autoantibodies can curtail platelet receptor function. Platelet ITAM receptor dysfunction may contribute to the increased bleeding phenotype observed in some patients with ITP. [source] Haemophilia and thrombophilia: an unexpected association!HAEMOPHILIA, Issue 4 2004Y. Dargaud Summary., In patients with haemophilia, a close correlation is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX clotting activity. However, some patients experience milder bleeding phenotypes than others, although they exhibit a similar biological profile. The high prevalence of some inherited thrombophilia risk factors offers the possibility of a co-inheritance in haemophilic patients which could influence the phenotypic expression of the disease. Rare thrombotic complications occurring in haemophiliacs could also be facilitated by the co-inheritance of modifier genes. The majority of thrombotic events occurring in haemophiliacs are in relation to clotting factor infusions or central venous catheters. Concerning surgical situations, in the absence of therapeutic recommendations, postoperative thromboprophylaxis is not systematically performed in haemophiliacs. However, substitutive treatment more or less completely corrects the coagulation defect and makes the venous thrombosis risk closer to the control population. It should be emphasized that haemophilia does not fully protect against venous thromboembolic disease. Patients with haemophilia very infrequently experience thrombotic events. Thus, the management of thrombotic complications occurring in haemophilic patients should be discussed in each case according to the precipitating risk factors, the clinical context and the thrombo-haemorrhagic balance of the patient with respect to a particular clinical situation. [source] Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profileJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2010E. SANTAGOSTINO Summary.,Background: Patients with severe hemophilia may show very varied bleeding tendencies, and the reasons for this heterogeneous clinical expression are unclear. The factor VIII/FIX genotype is the main determinant of the residual factor activity; however, different bleeding phenotypes have also been reported in patients sharing the same mutation. Such global coagulation tests as thrombin generation assays are tools with which to investigate different coagulation profiles among severe hemophiliacs. Objectives, patients and methods: This case,control study was aimed at comprehensively evaluating the role of genotype and endogenous thrombin potential (ETP) as predictors of the clinical phenotype in severe hemophiliacs with an extremely mild bleeding tendency (cases, n = 22), in comparison with those showing a typical bleeding tendency (controls, n = 50). Results: Cases were more frequently affected by hemophilia B than by hemophilia A, and showed a lower incidence of severe FVIII/FIX gene defects (referred to as null mutations), higher FVIII and FIX antigen levels and higher ETP values in platelet-rich plasma than controls (P < 0.05). By multivariate logistic regression, only non-null mutations were confirmed as an independent predictor of a mild clinical phenotype. Conclusions: These results indicate that non-null mutations represent the main determinant of the bleeding tendency, and that ETP measurement in platelet-rich plasma is able to identify severe hemophiliacs with a mild clinical phenotype. [source] | ||||||||||