Protein C Deficiency in Two Austrian Families

Summary

Protein C antigen was determined by Laurell rocket immunelectrophoresis in 225 patients with a history of venous thrombosis. Among these patients two females with protein C deficiency were detected. Additional studies in the families of the protein C deficient patients revealed further 7 family members with protein C deficiency. In 8 not anticoagulated patients with protein C deficiency the protein C ranged from 36 to 62% (median: 45%). In one patient on oral anticoagulant treatment protein C antigen concentration was < 10%, FII and F X were 65 and 50%, respectively. The pattern of inheritance was consistent with autosomal dominant inheritance. 5 of the 9 protein C deficient patients had severe thrombotic tendency characterized by recurrent deep venous thrombosis (n = 4), pulmonary embolism (n = 1), probable mesenteric vein thrombosis (n = 1) and superficial thrombophlebitis (n = 2). All protein C deficient patients without thrombosis were less than 17 years old.

Keywords

Protein C deficiency - Thrombotic disease

• References

• 1 Stenflo J. A new vitamin-K dependent protein. Purification from bovine plasma and preliminary characterisation J Biol Chem 1976; 251: 355-363
• 2 Kisiel W, Canfield WM, Ericsson LH, Davie EW. Anticoagulant properties of bovine plasma protein C following activation by throm-bin. Biochemistry 1977; 16: 5824-5831
• 3 Kisiel W. Human protein C. Isolation, characterisation and mechan-ism of activation by α-thrombin. J Clin Invest 1979; 64: 761-769
• 4 Kisiel W, Ericsson LH, Davie EW. Proteolytic activation of protein C from bovine plasma. Biochemistry 1976; 15: 4893-4900
• 5 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalized activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2245-2252
• 6 Marlar RA, Kleiss AJ, Griffin JH. Human protein C: inactivation of factor V and VIII in plasma by the activated molecule. Ann NY Acad Sci 1981; 370: 307-310
• 7 Canfield W, Nesheim M, Kisiel W, Mann GK. Proteolytic inactivation of bovine factor Va by bovine activated protein C. Circulation 1978; 58 (Supp II) (Suppl. 02) 210
• 8 Comp PhC, Esmon ChT. Activated protein C inhibits platelet prothrombin converting activity. Blood 1979; 54: 1272-1281
• 9 Dahlbäck B, Stenflo J. Inhibitory effect of activated protein C on activation of prothrombin by platelet-bound factor Xa. Eur J Biochem 1980; 107: 331-335
• 10 Comp PhC, Esmon ChT. Initiation of clot lysis in plasma by activated protein C. Circulation 1978; 58 (Supp II) (Suppl. 02) 210
• 11 Comp PhC, Esmon ChT. Generation of in vivo fibrinolytic activity by infusion of activated protein C into dogs. Circulation 1980; 62 (Supp) 334
• 12 Griffin JH, Evatt B, Zimmermann TS, Kleiss AJ, Widemann C. Deficiency of protein C in congenital thrombotic desease. J Clin Invest 1981; 68: 1370-1373
• 13 Bettina RM, Broekmans AW, van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemostas 1982; 48: 1-5
• 14 Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 (Supp) (Suppl. 124) 21-34
• 15 Bertina RM, Veltkamp JJ. A genetic variant of factor IX with decreased capacity for Ca²⁺binding. Br J Haematol 1979; 42: 623-635
• 16 Bertina RM, Marel van Nieuwkopp van der W, Loeliger EA. Spectrophotometric assays of prothrombin in plasma of patients using oral anticoagulants. Thromb Haemostas 1979; 42: 1296-1305
• 17 Bertina RM, Westhoek-Kuipers ME, Alderkamp GH. The inhibitor of prothrombin conversion in plasma of patients on oral anticoagulant treatment. Thromb Haemostas 1981; 45: 237-241
• 18 Ödegard OR, Lie M, Abildgaard U. Heparin cofactor activity measured with an amidolytic method. Thromb Res 1975; 6: 287-294
• 19 Lechner K. Laboratoriumsdiagnose hämatologischer Erkrankungen 2, Blutgerinnungsstörungen. Springer Verlag; Berlin-Heidelberg-New York: 1982
• 20 Korninger Ch, Niessner H, Lechner K. Impaired fibrinolytic response to DDAVP and venous occlusion in a subgroup of patients with von Willebrand’s disease. Thromb Res 1981; 23: 365-374
• 21 Broekmans AW, Bertina RM, Van der Linden IK. Protein C deficiency in three Dutch families with thrombotic disease. Haemo-stasis 1982; 12: 162
• 22 Thaler E, Lechner K. Antithrombin III deficiency and thrombo-embolism. Clin Haematol 1981; 369-390