Factor V, deficiency

Cui J, O Shea KS, Purkayastha A et al. (1996) Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature 384 66-68 Yang TL, Cui J, Taylor JM et al. (2000) Rescue of fatal neonatal hemorrhage in factor V deficient mice by low level transgene expression. Thromb Haemost 83 70-77... 

Factor V deficiency is cansed by prodnction of a labile protein. 

The prothrombin time was prolonged to 36 seconds, with isolated factor V deficiency (5%), 2 weeks after a 46-year-old patient with a liver transplant was given tacrolimus and oxaciUm (61). Factor V antigen was lower than 5%. In vitro investigations of the patient s plasma showed dose-dependent factor V inhibitory activity in the presence of tacrolimus. Factor V activity and the coagulation profile returned to normal after withdrawal. 

Proaccelerin Accelerator Globulin (Ac-G) V Factor V deficiency, (parahemophilia) Increased risk for thrombosis (Factor V Leiden) Extremely rare 7-10 0.025 Liver, megakaryocytes, endothelial cells 11-15 FA5 HUMAN... 

Oral anticoagulants, unless a dilution is made into Factor V-deficient plasma and a variation on a factor V specific assay is needed... 

A woman with factor V deficiency had several anaphylactic reactions to FFP despite premedication with antihistamines and glucocorticoids. Administration of leukodepleted FFP from the patient s brother was possible and did not cause adverse reactions [29 ]. 

Coppola A, Maruotti GM, Feola G, Catalano A, Quaglia F, Tomaiuolo M, Di Minno MN, Cerbone AM, Margaglione M, Martinelli P. Management of patients with factor V deficiency open issues from the challenging history of a woman with anaphylactic transfusion reactions. Haemophilia 2010 16(3) 560-3. 

A 25-year-old man with factor V deficiency developed TRALI after receiving 5 units of plasma he recovered completely [40 ]. However, recurrent TRALI developed after he was given 2 units of plasma 5 months later. 

Laga A, Kurtis J, Sweeney J. Recurrent transfusion-related acute lung injury after fresh frozen plasma in a patient with hereditary factor V deficiency. Am J Hematol 2008 83(8) 680. 

Interesting findings were recently reported by S0rbye and associates in a study of the factors concerned in the normal clotting mechanism. They isolated from the plasma of vitamin K-deficient chicks a protein factor, designated the kappa factor which reduced plasma prothrombin time in animals treated with bishydroxycoumarin (dicumarol) but which had no effect upon prothrombin time in vitamin K deficiency. A second factor, the delta factor, was isolated from plasma of chicks treated with dicumarol which reduced prothrombin time of plasma of vitamin K-deficient chicks but not that of plasma from chicks receiving dicumarol. They postulated that at least four factors are necessary in the clotting mechanism prothrombin proper, the kappa and delta factors, and the labile factor of fresh plasma (factor V). Deficiency of vitamin K apparently produced a defect in the delta factor, while administration of dicumarol produced a deficiency of the kappa factor. 

Hereditary deficiency of Factor V is a rare autosomal recessive disorder. Combined deficiencies of Factors V and VIII have been identified in several families. 

Combined deficiency of factors V and VIII, 227300 ERGIC-53, a mannosebinding lectin... 

Individuals with heterozygous protein C deficiency are seven times more likely to be afflicted with venous thrombosis than normal individuals. A combination of protein C deficiency with a mutation in the factor V gene (factor V Leiden) carries a much greater risk for venous thrombosis than the presence of only one of these conditions (89). 

Thrombogenic mutations (e.g., factor V Leiden, protein C or S deficiency, antithrombin III... 

Parahemophilia is an autosomal recessive bleeding disorder characterized by a reduced plasma concentration of the Factor V blood copulation protein. Deficiency arises from a 12 base-pair deletion in the Factor V gene that impairs the secretion of Factor V by hep-atocytes and results in an abnormal accumulation of immunoreactive Factor V antigen in the cytoplasm. In which region of the Factor V gene would this mutation most likely be located ... 

Proper duration of therapy is unclear in first event with homozygous Factor V Leiden, homocystinemia, deficiency of protein C or S, or multiple thrombophilias and in recurrent events with reversible risk factors. 

Data from the Leiden Thrombophilia Study have been used to construct a case-control study, based on contraceptive users who had experienced a first episode of objectively proven deep vein thrombosis (100). Patients and controls were considered thrombophilic when they had protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden mutation, or a prothrombin 20210 A mutation. Among healthy women, the risk of developing deep vein thrombosis was trebled in the first 6 months and doubled in the first year of contraceptive use. Among women with thrombophilia, the risk of deep vein thrombosis was increased 19-fold during the first 6 months and 11-fold (95% Cl = 2.1, 57) in the first year of use. Venous thrombosis during the first period of oral contraceptive use might actually point to the presence of an inherited clotting defect. 

The inherited disorders characterized by an tendency to form thrombi (thrombophilia) derive from either quantitative or qualitative abnormalities of the natural anticoagulant system. Deficiencies in the natural anticoagulants antithrombin, protein C, and protein S account for approximately 15% of selected patients with juvenile or recurrent thrombosis and 5-10% of unselected cases of acute venous thrombosis. Additional causes of thrombophilia include the factor V Leiden mutation, hyperhomocystinemia, and the prothrombin 20210 mutation that together account for the greater number of hypercoagulable patients. 

Bi, L., Sarkar, R., Naas, T., Lawler, A. M., Pain, J., Shumaker, S. L., Bedian, V. and Kazazian, H. H., Jr. (1996). Further characterization of factor VIII-deficient mice created by gene targeting RNA and protein studies. Blood 88, 3446-3450. 

Vandendriessche, T., Vanslembrouck, V., Goovaerts, I., Zwinnen, H., Vanderhaeghen, M. L., Collen, D. and Chuah, M. K. (1999). Long-term expression of human coagulation factor VIII and correction of hemophilia A after in vivo retroviral gene transfer in factor VUI-deficient mice. Proc. Natl. Acad. Sci. USA 96, 10379-10384. 

As low levels of protein C activation peptide are found in healthy individuals, it is suggested that protein C is constantly activated to a small degree (124). Protein C administration has been shown to inhibit both arterial and venous thrombosis in animal models (125). Heterozygous protein C deficiency or activated protein C resistance due to factor V mutation is thought to explain 60% to 70% of the cases of familial thrombophilia (I 16). 

Factor deficiencies include disorders of fibrinogen such as afibrinogenemia and dysfibrinogenemias, prothrombin deficiency, factor V VII, X, XI, XII, and XIII deficiency, prekallikrein and high-molecular-weight kininogen deficiency, combined factor deficiencies, a2 anti-plasmin deficiency, a] antitrypsin Pittsburgh, and protein Z deficiency. 

The inherited (primary) hypercoagulable states include activated protein C resistance due to the factor V Leiden mutation, prothrombin gene mutation, antithrombin deficiency, protein C or protein S deficiency, and dysfibrino-genemia. The most important cause of activated Protein C resistance is the defect in factor V involving the mutation of Arg506 to Gln506 (191). 

Lawler J, Sunday M, Thibert V et al. (1998) Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest 101 982-992 Bi L, Sarkar R, Naas T et al. (1996) Further characterization of Factor VUI-deficient mice created by gene targeting RNA and protein studies. Blood 88 3446-3450 Bugge TH, Suh TT, Flick MJ et al. (1995) The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility. J Bio Chem 270 16886-16894... 

Connolly AJ, Ishihara H, Kahn ML et al. (1996) Role of the thrombin receptor in development and evidence for a second receptor. Nature 381 516-519 Cui J, O Shea KS, Purkayastha A et al. (1996) Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature 384 66-68 Denis C, Methia N, Frenette PS et al. (1998) A mouse model of severe von Willebrand disease defects in hemostasis and thrombosis. Proc Nad Acad Sci USA 95 9524-9529 Dewerchin M, Liang Z, Moons L et al. (2000) Blood coagulation factor X deficiency causes partial embryonic lethality and fatal neonatal bleeding in mice. Thromb Haemost 83 185-190... 

Thrombophilia e.g. antithrombin III deficiency, protein C deficiency, factor V Leiden mutation, protein S deficiency, plasminogen abnormality or deficiency Leukemia/lymphoma Polycythemia... 

Thrombophilias and other causes of hypercoagulability are rare causes of stroke (Matijevic and Wu 2006). Antithrombin III deficiency, protein C deficiency, activated protein C resistance owing to factor V Leiden mutation, protein S deficiency and plasminogen abnormality or deficiency can all cause peripheral and intracranial venous thrombosis. Thrombosis is usually recurrent and there is often a family history. Thrombophilia may cause arterial thrombosis, although the alternative diagnosis of paradoxical embolism should always be considered in patients with these disorders. It should be noted that deficiencies in any one of the factors associated with thrombophilia may be an incidental finding and cannot necessarily be assumed to be the cause of stroke. 

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