Blood coagulation Deficiencies

The main goal of recessively inherited coagulation disorder (RICD) treatment is to prevent and control spontaneous and surgery-related bleeding episodes. Specifically, therapeutic options improve hemostasis via replacement of deficient blood coagulation factors while minimizing the development of immune tolerance.20... 

Several substances that contribute to the blood coagulation process are formed in the liver. These include fibrinogen, prothrombin, and several of the blood clotting factors (II, VII, IX, and X). Deficiency in any of these substances leads to impaired blood coagulation. 

Vitamin K (phylloquinone) and similar substances with modified side chains are involved in carboxylating glutamate residues of coagulation factors in the liver (see p. 290). The form that acts as a cofactor for carboxylase is derived from the vitamin by enzymatic reduction. Vitamin K antagonists (e. g., coumarin derivatives) inhibit this reduction and consequently carboxylation as well. This fact is used to inhibit blood coagulation in prophylactic treatment against thrombosis. Vitamin K deficiency occurs only rarely, as the vitamin is formed by bacteria of the intestinal flora. 

Mechanism of Action An electrolyte that is essential for the function and integrity of the nervous, muscular, and skeletal systems. Calcium plays an important role in normal cardiac and renal function, respiration, blood coagulation, and cell membrane and capillary permeability. It helps regulate the release and storage of neurotransmitters and hormones, and it neutralizes or reduces gastric acid (increase pH). Calcium acetate combines with dietary phosphate to form insoluble calcium phosphate. Therapeutic Effect Replaces calcium in deficiency states controls hyperphosphatemia in end-stage renal disease. 

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... 

Gailani D, Lasky NM, Broze GJ (1997) A murine model of factor XI deficiency. Blood Coagul Fibrinolysis 8 134-144... 

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... 

Gailani D, Lasky NM, Broze GJ (1997) A murine model of factor XI deficiency. Blood Coagul Fibrinolysis 8 134-144 Healy AM, Rayburn HB, Rosenberg RD, Weiler H (1995) Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc Natl Acad Sci USA 92 850-854... 

Cystic fibrosis patients are usually advised to take more than the recommended daily amounts of these vitamins in order to prevent deficiency. A common problem associated with poor absorption of fat-soluble vitamins is deficiency of vitamin K. Vitamin K is required by the liver to produce many blood coagulation factors. Part of the problem for cystic fibrosis patients is their chronic antibiotic therapy, which decreases the bacterial population of the colon colonic bacteria synthesize vitamin K. Vitamin K deficiency leads to prolonged blood-clotting time. Vitamin D deficiency could cause rickets in a child or osteomalacia in adults. Vitamin A deficiency leads to night blindness, skin and other ocular defects. 

Other at-risk groups are hospitalized patients with poor nutrient intakes or those receiving TPN, when fat-soluble vitamin supplements may not fuUy meet requirements. Conversely, ingestion of supraphysiological doses of vitamins A and E has also been reported to induce vitamin K deficiency, probably by competitive mechanisms. Defective blood coagulation and demonstration of abnormal noncar-boxylated prothrombin are at present the only well-established signs of vitamin K deficiency. 

The answer is e. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 121—144. Wilson, pp 23—98.) Hemophilia A is caused by deficiency of factor VIII and hemophilia B by deficiency of factor IX. Both factors are involved in the intrinsic blood coagulation pathway that results in activation of factor X. Alternatively, factor X can be activated by tissue factors through the extrinsic blood coagulation pathway Activated factors X and V produce thromin from prothrombin, which in turn cleaves fibrinogen to produce fi-... 

Phytonadione is used to treat vitamin K deficiency. The dose, frequency, and duration of vitamin K depend on the severity of the deficiency and the patient s response. Vitamin K may be administered orally, intramuscularly, subcutaneously, or intravenously. After an oral dose of vitamin Kj, the blood coagulation factors increase within 6 to 12 hours. When administered parenterally, the PT may take 12 to 24 hours to normalize, although improvement usually occurs within 1 to 2 hours. Failure to correct the PT after 48 hours should raise suspicion aboutthe etiology of the coagulation abnormality (e.g., liver disease). 

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