Factor VII, deficiency

Deficiency of Factor VII is relatively rare and inherited as an autosomal recessive disorder. Deficiency of Factor VII has been reported to be associated with bond abnormal bleeding and thrombotic tendencies. Deep vein thrombosis and pulmonary emboli have been reported in affected individuals. There is a very high frequency of Factor VII deficiency in people with the Dubin-Johnson syndrome, which is a congenital disorder of Hver function. 

VII Factor VII deficiency 30% 4-6 hours FFP Prothrombin complex concentrates (intermediate... 

The development of antibodies against recombinant factor Vila or hjrpersensitivity reactions to normal doses of recombinant factor Vila have not so far been reported (7). No antibodies against recombinant factor Vila were observed in a group of 222 hemophilia A and 16 hemophilia B patients with inhibitors treated with high doses of factor Vila (14). However, antibodies to factor VII have been observed in a patient with factor VII deficiency who received 40 times the recommended dose of recombinant activated factor Vila (3). Another case of low-titer and transient factor VII antibody formation has been reported in a patient with factor VII deficiency (10). 

Scharrer I. Recombinant factor Vila for patients with inhibitors to factor VIII or IX or factor VII deficiency. Haemophilia 1999 5(4) 253-9. 

Proconvertin, Plasma thromboplastin VII Factor VII deficiency, increased risk of thrombosis with elevated F-VII concentration Rare 2 per 1,000,000 0.5 0.01 Liver 4-5 IDAN FA7 HUMAN... 

In general, the Factor VII activity estimated by a substrate assay correlated well with Factor VII activity determined by a clot-endpoint assay (P4, S13). However, some differences have been seen. Activation of Factor VII by kaolin or by exposure to cold temperatures (2-8°C) increased the level of clotting Factor VII by 4-7 times but bad no effect on the amount detected by the substrate assay (S9, TIO). It has been postulated that the partially carbox-ylated molecules of Factor VII present in patients plasma during anticoagulant therapy are detected by a substrate assay but not in a clot-endpoint test (P4). These differences between the two assay systems have been used to screen for hereditary Factor VII deficients and to detect the presence of Factor Vila in thrombotic disorders and in components for transfusion therapy (S13). 

Factor IX complex, a blood derivative with hemostatic properties, is used in factor IX deficiency (hemophilia B or Christmas disease) in patients with factor VIII inhibition, in factor VII deficiency, and in overdosage with anticoagulant (see also Tables 17 and 18 and Figure 92). 

Factor IX is an antihemophilic agent that restores hemostasis in patients with factor IX deficiency. It is indicated in the control and prevention of hemorrhagic episodes in patients with hemophilia B (factor IX deficiency) (Proplex T only) bleeding episodes in patients with inhibitors to factor VIII, and prevention or control of bleeding episodes in patients with factor VII deficiency. 

Table 4 contains products available for Factor VII, Factor VIIFC (hemophilia A), Factor IX, and von Willebrand protein deficiency. Table 5 fists miscellaneous hemostatics and thein proposed mechanisms of action. 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Proplex T (Factor IX Complex)—used for factor VIII inhibitors, and factor VII or IX deficiency... 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

Freeze-dried concentrates of plasma containing prothrombin, factors IX and X, and varied amounts of factor VII (Proplex, etc) are commercially available for treating deficiencies of these factors (Table 34-3). Each unit of factor IX per kilogram of... 

The most obvious effect of a deficiency in vitamin K in animals is delayed blood clotting, which has been traced to a decrease in the activity of prothrombin and of clotting factors VII, IX, and X (Chapter 12, Fig. 12-17). Prothrombin formed by the liver in the absence of vitamin K lacks the ability to chelate calcium ions essential for the binding of prothrombin to phospholipids and to its activation to thrombin. The structural differences between this abnormal protein and the normal prothrombin have been pinpointed at the N terminus of the 560 residue glycoprotein.e f Tryptic peptides from the N termini differed in electrophoretic mobility. As detailed in Chapter 12, ten residues within the first 33, which were identified as glutamate residues by the sequence analysis on normal prothrombin, are actually y-carboxyglutamate (Gla). The same amino acid is present near the N termini of clotting factors VII, IX, and X. 

Morrissey JH, Mack BG, Neuenschwander PR Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation, Blood 1993 81 734-744. 

Fresh frozen plasma (FFP) 250 ml at six-hour intervals (10-20 ml/kg BW = 1,000-1,500 ml/day). Administration of 10 ml/kg BW (about 600-1,200 rnl) serves to elevate the concentrations of coagulation factors and inhibitors by 15—20%. The half-life of factor VII is only 6 hours, which is why dosage intervals of 6 to 12 hours must be maintained. IgA deficiency is a known contraindication. Adverse transfusion reactions may occur with a frequency of 1-5% of cases. Improvement in coagulopathy generally lasts 1 to 2 days. Caution is called for, since accentuated coagulation entails the danger of thrombosis (if necessary, AT III replacement of up to 60-80%), and an overload of the intra-... 

Transient protein C deficiency can be induced when initiating treatment with warfarin because factors VII and protein C have the shortest half-lives of the coagulation factors (Table VII-1-2). Consequently, the extrinsic pathway and protein C system are inactivated, whereas the intrinsic system remains active for a few days. Hypercoagulability occurs (Figure VII-1-2), which may result in dermal vascular thrombosis and skin necrosis. 

Phytonadione is a blood modifier/vitamin K. It promotes hepatic synthesis of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX) and Stuart factor (factor X). It is indicated in the management of coagulation disorders due to faulty formation of factors II, Vn, IX, and X due to vitamin K deficiency or interference with vitamin K activity. Oral/parenteral used for treatment of anticoagulant-induced prothrombin deficiency treatment of hypoprothrombinemia secondary to salicylates or antibacterial therapy, or secondary to obstructive jaundice and biliary fistulas, provided bile salts are also given. Parenteral used for treatment of hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K prophylaxis and therapy of hemorrhagic disease of the newborn. 

Transient protein C deficiency can be induced when initiating treatment with warfarin because factors VII and protein C have the shortest half-lives of the coagulation factors (Table VII-1-2). 

Flemophilia A and B coagulation defects, which are caused by deficiencies of Factor VIII and Factor IX, respectively, can be bypassed by administration of recombinant Factor Vila. Flowever, the short half-life of recombinant Factor Vila in vivo negates its routine clinical use. An in vivo method for the continnons generation of Factor Vila is reported which depends on tlie implantation of a porous chamber that contains Factor Xa or Xlla and continuously generates Factor Vila bypass activity from the subject s own Factor VII, which enters the chamber by diffusion. Once inside, the Factor VII is cleaved to Factor Vila by the immobilized Factor Xa or Xlla. Tlie newly created Factor Vila diffuses ont of the chamber and back into cuculation, where it can bypass the deficient Factors VIII or DC and enable coagulation to occur. In vitro, tliis method generates sufficient Factor Vila to sub-... 

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