Summary
Hemorrhagic skin necrosis of the toes was observed in a patient with heterozygous protein C deficiency (protein C:Ag 32% and protein C activity 30%) on the 4th day of coumarin treatment overlapping with effective intravenous anticoagulation with heparin. Family studies revealed protein C deficiency in two sisters of the proposita without a history of thromboembolic disease. Immunologic studies in the proposita at the time of coumarin necrosis revealed slight depression of complement factor C4 and the presence of immune complexes. The present case and review of the literature show that the pathogenetic mechanism leading to coumarin necrosis in patients with protein C deficiency seems not yet to be fully understood.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amstel van WJ, Boekhout-Mussert MJ, Loeliger EA (1978) Successful prevention of coumarin induced hemorrhagic necrosis by timely administration of vitamin K. Blut 36: 89–93
Bahadir I, Forks G, James EC, Fedde CW (1977) Soft tissue necrosis and gangrene complicating treatment with the coumarin derivatives. Surg Gynecol Obstet 145: 497–500
Bertina RM, Broekmans AW, Van der Linden IK, Mertens K (1982) Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 48: 1–5
Branson HE, Katz J, Marble R, Griffin JM (1983) Inherited protein C deficiency and coumarin responsive chronic relapsing purpury fulminans in a newborn infant. Lancet 2: 1165–1168
Broekmans AW, Bertina RM, Loeliger EA, Hofman V, Klingemann HG (1983) Protein C and the development of skin necrosis during anticoagulant therapy. Thromb Haemost 49: 244
Deutsch E, Frischauf H, Grünberger V (1950) Zwischenfälle der Dicumarolbehandlung und ihre Therapie. Z Klin Med 147: 324–333
DiCato MA, Ellman L (1975) Coumarin induced necrosis of breast, disseminated intravascular coagulation and hemolytic anemia. Ann Intern Med 83: 233–234
Estelles A, Garcia-Plaza I, Dasi A, Aznar J, Duart M, Sanz G, Perez-Requejo JL, Espana F, Jimenez C, Abeledo G (1984) Severe inherited “homozygous” protein C deficiency in a newborn infant. Thromb Haemost 52: 53–56
Everett ME, Overholt CE (1969) Hemorrhagic skin infarction secondary to oral anticoagulants. Arch Dermatol 100: 588–591
Faraci PA, Deterling RA, Stein AM, Rheinlander HF, Cleveland RJ (1978) Warfarin induced necrosis of the skin. Surg Gynecol Obstet 146: 695–700
Flood EP, Redish MH, Bociek SJ, Shapiro S (1943) Thrombophlebitis migrans disseminata: Report of a case in which gangrene of a breast occurred. N J State J Med 43: 1121–1124
Francis RB, Patch MJ (1983) A functional assay for protein C in human plasma. Thromb Res 32: 605–613
Hofmann V, Frick PG (1982) Repeated occurrence of skin nekrosis twice following coumarin intake and subsequently during decrease of vitamin K dependent coagulation factors associated with cholestasis. Thromb Haemost 48: 245–246
Klingemann HG, Egbring R (1982) Die Kumarinnekrose. Med Welt 33: 676–677
Kudr J (1956) Akute thrombophlebitische Nekrose der Bauchhaut. Zentralbl Chir 81: 137
Lechner K (1982) Laboratoriumsdiagnostik hämatologischer Erkrankungen. 2. Blutgerin-nungsstörungen. Springer, Berlin Heidelberg New York
Lieb L (1964) Über die “Kumarinnekrose” und ihre Beziehung zum Schwartzman-Sanarelli-Phänomen. Zentralbl Chir 3: 81–89
Loeliger EA, Broekmans AW (1984) Drugs affecting blood clotting and fibrinolysis. In: Dukes MNG, Elis G, Griffin GT, Heignét R, Mahon GH, Nix G, Tester-Dalderup CBM, van Eichstedt K-W, Westerholm B (eds) Meyler's side effect of drugs. 10th edition, pp 659–661. Amsterdam, Oxford, Princeton: Excerpta Medica
Marciniak E, Wilson HD, Marlar RA (1985) Neonatal purpura fulminans: A genetic disorder related to the absence of protein C in blood. Blood 65: 15–20
McGehee WG, Klotz TA, Epstein DJ, Rapaport SI (1984) Coumarin necrosis associated with hereditary protein C deficiency. Ann Intern Med 100: 59–60
Nalbandian RM, Mader IJ, Barrett JL, Pearce JF, Rupp EC (1965) Petechiae, ecchymoses and necrosis of skin induced by coumarin congeners. JAMA 17: 603–608
Pabinger-Fasching I, Bertina RM, Lechner K, Niessner H, Korninger C (1983) Protein C deficiency in two Austrian families. Thromb Haemost 50: 810–813
Pabinger I (1985) Protein C Mangel. Hämostaseologie 5: 134–138
Pabinger I, Deutsch E (1985) Protein C deficiency in Austria. Semin Thromb Hemost 11: 347–351
Rose VL, Fareed J, Kwaan HC (1985) Protein C:Ag deficiency and coumarin necrosis. Thromb Haemost 54: 144
Samama M, Horellou MH, Soria J, Conard J, Nicolas G (1984) Successful progressive anti-coagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemost 51: 132–133
Schleicher SM, Fricker MP (1980) Coumarin necrosis. Arch Dermatol 116: 444–445
Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin A, Rapaport SI (1984) Homozygous protein C deficiency manifested by massive venous thrombosis in a newborn. N Engl J Med 310: 559–562
Verhagen H (1954) Local haemorrhage and necrosis of the skin and underlying tissues, during anticoagulant therapy with dicoumarol or dicoumaryl. Acta Med Scand 148: 453–461
Vigano S, Mannucci PM, Solinas S, Bottasso B, Mariani G (1984) Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 57: 213–220
Weinberg AC, Lieskovsky G, McGehee WG, Skinner DG (1983) Warfarin necrosis of the skin and subcoutanous tissue of the male external genitalia. J Urol 130: 352–354
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pabinger, I., Karnik, R., Lechner, K. et al. Coumarin induced acral skin necrosis associated with hereditary protein C deficiency. Blut 52, 365–370 (1986). https://doi.org/10.1007/BF00320783
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00320783