The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform
David J Perry - One of the best experts on this subject based on the ideXlab platform.
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Factor X deficiency
Blood Reviews, 2002Co-Authors: James Uprichard, David J PerryAbstract:Abstract Factor X is one of the vitamin K-dependent serine proteases. It plays a crucial role in the coagulation cascade, as the first enzyme in the common pathway of thrombus formation. The gene for Factor X maps to the long arm of chromosome 13, approXimately 2.8 kb downstream of the Factor VII gene. The gene consists of eight eXons, each of which encodes a specific functional domain within the protein. Both the gene structure and the amino acid sequence show homology to other vitamin K-dependent clotting Factors, suggesting their origin in a common ancestral protein. Factor X deficiency is one of the rarest of the inherited coagulation disorders. Inheritance is in an autosomal recessive manner. The clinical phenotype is of a variable bleeding tendency. Homozygous Factor X deficiency has an incidence of 1:1, 000, 000 in the general population. Heterozygotes are often clinically asymptomatic. Acquired Factor X deficiency is rare, but when it occurs it is usually in association with amyloidosis. Treatment of Factor X deficiency involves replacement of the protein with either fresh frozen plasma or prothrombin compleX concentrates, although the latter should be used with caution as infusion may be associated with an increased risk of thrombosis.
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congenital Factor X deficiency spectrum of bleeding symptoms in 32 iranian patients
British Journal of Haematology, 1998Co-Authors: Flora Peyvandi, Pier Mannuccio Mannucci, M Abdoullahi, Sirous Zeinali, R Sharifian, David J PerryAbstract:The spectrum of the clinical manifestations of congenital Factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaXis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable Factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an uneXpected finding in nine patients. This study demonstrated that the bleeding tendency of Factor X deficiency is severe and correlates with Factor levels.
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Factor X and its deficiency states
Haemophilia, 1997Co-Authors: David J PerryAbstract:Summary. Factor X is one of the vitamin-K-dependent serine proteases. As a result of its position at the convergence of the intrinsic and eXtrinsic pathways of the clotting cascade, it plays a crucial role in blood coagulation. Factor X interacts with components of both pathways of coagulation, leading to its activation and the formation of the prothrombinase compleX. The gene for Factor X has been cloned and sequenced and maps to the long arm of chromosome 13, approXimately 2.8 kb downstream of the Factor VII gene. Each of the eXons of Factor X encodes a specific functional domain within the protein. In terms of its gene structure and amino acid sequence, Factor X shows significant homology with other vitamin-K-dependent clotting Factors, suggesting an origin in some common ancestral protein. Factor X deficiency is one of the rarest of the inherited coagulation disorders. Such deficiencies are inherited in an autosomal recessive manner and are characterized by a variable bleeding tendency. In its homozygous form, Factor X deficiency has an estimated prevalence of 1:500 000 but in its heterozygous form it has an estimated frequency of ∼1:500 although affected individuals are often clinically asymptomatic. Acquired deficiencies of Factor X are uncommon and in isolation are seen most frequently in patients with amyloidosis and in association with upper respiratory tract infections. Treatment of the deficiency state involves Factor X replacement with either fresh frozen plasma or prothrombin compleX concentrates. However, the latter may be associated with an increased risk of thrombosis.
Flora Peyvandi - One of the best experts on this subject based on the ideXlab platform.
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Factor X deficiency
Seminars in Thrombosis and Hemostasis, 2009Co-Authors: Marzia Menegatti, Flora PeyvandiAbstract:Factor X (FX) deficiency is a rare, recessively inherited bleeding disorder representing 10% of all rare bleeding diseases and affecting 1 in every 1,000,000 people. Its clinical presentation places FX deficiency among the most severe of the rare coagulation defects, typically including hemarthroses, hematomas, and umbilical cord, gastrointestinal, and central nervous system bleeding. Phenotype diagnosis is based on the concomitant prolongation of the prothrombin time and activated partial thromboplastin time. Through the measurement of plasma level of FX antigen and its coagulant activity, two main types of deficiency can be distinguished: type I (concomitantly low levels of activity and antigen) and type II (low coagulant activity, but normal or borderline antigen levels). FX protein is mainly synthesized by the liver and is encoded by a gene ( F10) of 27 kb located on chromosome 13, containing 8 eXons. One hundred five mutations on F10 have been identified to date, 78% being missense mutations, with no hot-spot regions. There is no specific FX concentrate available, and current treatment includes the administration of fresh-frozen plasma or prothrombin compleX concentrates (PCCs) containing FX in addition to other vitamin K-dependent Factors. Administration of PCCs is associated with the risk of thromboembolic complication due to the unknown concentrations of other coagulant Factors; however, to overcome this problem, a concentrate containing well-defined amounts of FX (and FIX) has recently been developed.
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congenital Factor X deficiency spectrum of bleeding symptoms in 32 iranian patients
British Journal of Haematology, 1998Co-Authors: Flora Peyvandi, Pier Mannuccio Mannucci, M Abdoullahi, Sirous Zeinali, R Sharifian, David J PerryAbstract:The spectrum of the clinical manifestations of congenital Factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaXis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable Factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an uneXpected finding in nine patients. This study demonstrated that the bleeding tendency of Factor X deficiency is severe and correlates with Factor levels.
Howard A Liebman - One of the best experts on this subject based on the ideXlab platform.
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a fatal bleeding disorder due to antibody mediated acquired Factor X and prothrombin deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Donald I Feinstein, Gregory J Del Zoppo, Howard A LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and prothrombin deficiency. The patient’s plasma contained a non-inhibitory IgG antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 miX of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an eXtensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 miX. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-prothrombin antibodies directed were isolated by affinity chromatography on prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated antibody with prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-prothrombin antibody failed to demonstrate any prothrombin contamination of these proteins. A competition ELISA using prothrombin, Factor X and Factor IX showed that the antibody had a 3-fold greater affinity to Factor X then prothrombin. A Western blot using purified prothrombin fragment F1.2 confirmed that the antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and eXpired. We previosuly reported a lymphoma patient who developed acquired prothrombin deficiency associated with a non-inhibitory antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin deficiency due to a cross-reactive non-inhibitory IgG antibody.
R Sharifian - One of the best experts on this subject based on the ideXlab platform.
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congenital Factor X deficiency spectrum of bleeding symptoms in 32 iranian patients
British Journal of Haematology, 1998Co-Authors: Flora Peyvandi, Pier Mannuccio Mannucci, M Abdoullahi, Sirous Zeinali, R Sharifian, David J PerryAbstract:The spectrum of the clinical manifestations of congenital Factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaXis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable Factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an uneXpected finding in nine patients. This study demonstrated that the bleeding tendency of Factor X deficiency is severe and correlates with Factor levels.
Sirous Zeinali - One of the best experts on this subject based on the ideXlab platform.
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congenital Factor X deficiency spectrum of bleeding symptoms in 32 iranian patients
British Journal of Haematology, 1998Co-Authors: Flora Peyvandi, Pier Mannuccio Mannucci, M Abdoullahi, Sirous Zeinali, R Sharifian, David J PerryAbstract:The spectrum of the clinical manifestations of congenital Factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaXis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable Factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an uneXpected finding in nine patients. This study demonstrated that the bleeding tendency of Factor X deficiency is severe and correlates with Factor levels.
