Defibrination During Warfarin Therapy in a Man with Protein C Deficiency

Summary

A 57 year old man presented with apparently spontaneous lower extremity deep vein thrombosis and pulmonary embolism. He was treated in conventional fashion with intravenous heparin and oral warfarin. After 4 daily doses of warfarin the prothrombin and proconvertin (P+P) time was within therapeutic range, and heparin was stopped. Over the next six hours complete defibrination occurred, associated with severe bleeding complications. Functional protein C measured after normalization of routine coagulation tests averaged 40% of normal, and was only 3.5% of normal immediately prior to the episode of defibrination. We conclude that the very low functional protein C levels seen immediately prior to defibrination were caused by a combination of pre-existent protein C deficiency and warfarin therapy, and directly predisposed to defibrination once heparin was stopped, despite “therapeutic” warfarin anticoagulation. Exacerbation of intravascular coagulation should be considered a potential prothrombotic effect of warfarin therapy in protein C deficient individuals.

Keywords

Protein C deficiency - Warfarin therapy - Disseminated intravascular coagulatione

• References

• 1 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 70: 1370-1376
• 2 Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families N Engl J Med 1983; 309: 340-344
• 3 Bertina RM, Broekmans AW, Krommenhoek-van ES C, van Wijngaarden A. The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemostas 1984; 51: 1-5
• 4 Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin A, Rapaport SI. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med 1984; 51: 559-562
• 5 Sills RH, Humbert JR, Montgomery RR, Marlar RA. Clinical course and therapy of an infant with severe “homozygous” protein C deficiency. Blood 1983; 62: 310 a (Abstr)
• 6 Griffin JH, Mosher DF, Zimmerman TS, Kleiss AJ. Protein C, an antithrombotic protein, is reduced in hospitalized patients with intravascular coagulation. Blood 1982; 60: 261-264
• 7 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; 2: 463-467
• 8 McGehee WG, Klotz TA, Epstein DJ, Rapaport SI. Coumarin necrosis associated with hereditary protein C deficiency. Ann Int Med 1984; 101: 59-60
• 9 Broekmans AW, Bertina MR, Loeliger EA, Hofmann V, Klingemann HG. Protein C and the development of skin necrosis during anticoagulant therapy. Thromb Haemostas 1983; 49: 251
• 10 Feinstein DI, Rapaport SI, McGehee WG, Patch MJ. Factor V anticoagulants: clinical, biochemical, and immunological observations. J Clin Invest 1970; 49: 1578-1589
• 11 Kidder WR, Logan LJ, Rapaport SI, Patch MJ. The plasma protamine paracoagulation test: clinical and laboratory evaluation. Am J Clin Pathol 1972; 58: 675-686
• 12 Owren PA, Aas K. Hie control of dicumarol therapy and the quantitative determination of prothrombin and convertin. Scand J Clin Lab Invest 1951; 3: 201-208
• 13 Francis Jr RB, Patch MJ. A functional assay for protein C in human plasma. Thromb Res 1983; 32: 605-613
• 14 Branson HE, Marble R, Katz J, Griffin JH. Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; 2: 1165-1168
• 15 Sack GH, Levin J, Bell WR. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine 1977; 56: 1-34
• 16 Wajima T. Thrombophlebitis in cancer patients. Ann NY Acad Sci 1981; 370: 139-144
• 17 Sack Jr GH, Levin J, Bell WR. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine 1977; 56: 1-44