1/37. The impact of Glu102Lys on the factor X function in a patient with a doubly homozygous factor x deficiency (Gla14Lys and Glu102Lys).Two homozygous point mutations were found in a patient with factor X (FX) deficiency; One results in substitution of Lys for Gla 14 and the second causes a Lys substitution for Glu102. The proposita has a severely reduced FX coagulant activity in the extrinsic (<1% of normal) and in the intrinsic (30% of normal) system of coagulation and after activation with Russel's viper venom (18% of normal). The FX antigen is reduced in this patient to 20% of normal. The substitution of Lys for Glu102 in FX deficiency has been reported previously in a heterozygous state in conjunction with a Lys for Gla 14 substitution and with a Pro for Ser334 substitution. The contribution of the Lys for Glu102 substitution in the observed combined FX defect in these patients was unclear. The mutation causing the Glu102Lys substitution was introduced by site directed mutagenesis into a wild-type FX cDNA, and recombinant protein was expressed in HEK 293 cells. Compared to the wild-type FX cDNA, the mutant construct had a 67% activity upon activation in the extrinsic system, 93% activity upon activation in the intrinsic system and 72% after activation with RVV. The data presented show that the substitution of Lys for Glu102 results in a minor functional defect of the FX molecule.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
2/37. Combined deficiency of factors II, VII, IX, and X (Borgschulte-Grigsby deficiency) in pregnancy.BACKGROUND: Combined deficiency of vitamin k-dependent coagulation factors (II, VII, IX, X) is an uncommon challenge for the expectant gravida. CASE: A 34-year-old primigravida had congenital combined deficiency of factors II, VII, IX, and X that were incompletely sensitive to vitamin k. She had an altered form of vitamin k-dependent factors that retained immunologic activity but lacked coagulant activity and the normal complement of gamma-carboxyglutamic acid residues. She required vitamin k supplementation throughout her life. After an uneventful pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh frozen plasma was administered to achieve hemostasis. The remainder of her postpartum course was normal. CONCLUSION: Combined congenital deficiency of factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin k and fresh frozen plasma.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
3/37. danazol therapy in factor x deficiency.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.- - - - - - - - - - ranking = 25.747959134891keywords = coagulation disorder, coagulation (Clic here for more details about this article) |
4/37. A rare cause of intracranial hemorrhage: factor x deficiency.Congenital factor x deficiency is a rare inherited coagulation disorder, characterized by prolonged prothrombin time and partial thromboplastin time. For the definite diagnosis, specific factor X level should be investigated. We describe a patient with factor x deficiency who had intracranial hemorrhage. hematologic tests showed prolonged prothrombin time, partial thromboplastin time, and a factor X level of 5%. The patient's hemorrhage resolved with fresh frozen plasma replacement. In this article, we discuss the clinical features and management of factor x deficiency.- - - - - - - - - - ranking = 1265.8548182213keywords = inherited coagulation disorder, inherited coagulation, coagulation disorder, coagulation (Clic here for more details about this article) |
5/37. Reduced activation of the Gla19Ala FX variant via the extrinsic coagulation pathway results in symptomatic CRMred FX deficiency.We characterized a symptomatic CRMred factor X (FX) deficiency produced by the Glu19Ala mutation in the gamma-carboxyglutamic-rich domain. FX activity levels in plasma were markedly reduced in prothrombin time assays (< 1-5%), whereas in activated partial thromboplastin assays (16%) and in RVV assays (17%) the reduction in activity mirrored that in antigen levels (17%). Activation of recombinant 19Ala-FX by factor ixa/factor viiia or RVV, and the activity in thrombin generation assays, were comparable to those of wild-type FX. Differently, complete activation of recombinant 19Ala-FX required a factor viia/TF concentration 30-fold higher than that of wild-type FX. The recombinant FVIIa significantly reduced PT values in 19Ala-FX reconstituted plasma, thus suggesting an alternative approach for treatment of FX deficiencies characterized by defective FX activation. The study of this FX deficiency provides an "in vivo" and "in vitro" model for the investigation of Gla domain interactions.- - - - - - - - - - ranking = 4keywords = coagulation (Clic here for more details about this article) |
6/37. The role of primary prophylactic factor replacement therapy in children with severe factor x deficiency.Severe factor X (FX) deficiency is one of the severest inherited coagulation disorders. Clinical manifestations include umbilical cord, mucosal, joint and central nervous system bleeding. Four Irish children with severe FX deficiency presented with umbilical cord bleeding. One developed an intraperitoneal haemorrhage and another an intracranial bleed. Prophylaxis, using intermediate purity Factor IX concentrate, was commenced within the first month of life, necessitating the insertion of central venous access devices in two of the children. All children have normal joint function, suggesting that prophylaxis commenced early in life reduces the incidence of arthropathy and improves quality of life.- - - - - - - - - - ranking = 1265.8548182213keywords = inherited coagulation disorder, inherited coagulation, coagulation disorder, coagulation (Clic here for more details about this article) |
7/37. A novel type I factor X variant (factor X Cys350Phe) due to loss of a disulfide bond in the catalytic domain.We report a novel mutation within the coagulation factor X (FX) that we have designated FX Padua 4. The phenotype and genotype of the proband and family members were studied. The proband was a child affected by a complex neurological syndrome who, after birth, experienced severe bleeding. The proband showed a laboratory pattern characterized by a severe reduction of FX activity and FX antigen, suggesting a true deficiency. Molecular analysis disclosed a new FX mutation localized in the catalytic domain responsible for a Cys350Phe substitution. The proband was homozygous for this mutation. The proband's mother and father showed a heterozygous pattern and had approximately one-half the normal FX activity and FX antigen. Residual purified FX Cys350Phe had an identical behavior to normal FX as showed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Molecular modeling confirms that the mutation leads to the disruption of a disulfide bridge in the catalytic region of FX. Comparison with other topologically equivalent mutations in other vitamin k-dependent proteins suggests that this disruption could adversely affect protein folding/stability, accounting for the cross-reactive material negative phenotype.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
8/37. Spontaneous rupture of the spleen in AL amyloidosis.The frequency of splenic involvement in AL amyloidosis is not precisely known. However, splenomegaly has been reported in 4-13% of patients. We report four cases of spontaneous splenic rupture in patients with AL amyloidosis. splenic rupture was the initial manifestation of the disease in one of these patients. The other three experienced splenic rupture during or after high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT): one during stem cell mobilization with G-CSF prior to HDM/SCT and two after hematopoietic recovery following treatment. Two of the four patients had factor x deficiency, the most common coagulation abnormality associated with AL amyloidosis. All four patients underwent splenectomy without significant postoperative complications. splenic rupture in AL amyloidosis as a complication of aggressive treatment with HDM/SCT has not been reported previously.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
9/37. A unique circulating inhibitor with specificity for coagulation factor X.An 84-year-old woman presented with extensive cutaneous and gastrointestinal bleeding. Initial laboratory studies revealed a prolonged prothrombin time and activated partial thromboplastin time. Further investigations revealed a circulating anticoagulant with specificity for factor X. The patient's hemorrhage resolved with supportive measures only. Approximately 11 months after presentation, the inhibitor disappeared.- - - - - - - - - - ranking = 4keywords = coagulation (Clic here for more details about this article) |
10/37. A rare inherited coagulation disorder: combined homozygous factor VII and factor X deficiency.The combined presence in the homozygous state of more than one recessively transmitted coagulation defect may rarely occur in countries with a high rate of consanguinity. In an Iranian family consisting of two parents (second cousins) and two affected siblings, initial phenotypic analysis led to a diagnosis of mild FX deficiency (10-19% FX activity, 42-54% FX:Ag), and genotyping revealed a new homozygous missense mutation in the corresponding gene (Ser3Cys). As both of the sibs had a severe bleeding history that was not compatible with mild deficiency of FX, further phenotypic analysis revealed the additional presence of severe FVII deficiency (<1% FVII activity; 63-111% FVII:Ag) associated with the homozygous missense gene mutation Cys310Phe. In this kindred, lack of identification of the double coagulation defect might have led not only to incomplete understanding of the clinical phenotype but also to an incorrect prenatal diagnosis.- - - - - - - - - - ranking = 5065.4192728851keywords = inherited coagulation disorder, inherited coagulation, coagulation disorder, coagulation (Clic here for more details about this article) |
| | Next -> |