Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Arterial thrombosis as clinical manifestation of congenital protein C deficiency

  • 36 Accesses

  • 32 Citations


A 49-year-old man was hospitalized for slight paresis of the upper left limb. Thrombosis of the right internal carotid artery was documented by arteriography and digital angiography, which showed evidence of an anastomotic blood flow. He went on anticoagulation treatment. Five years later, after an uneventful period, he was referred to our center for the occurrence of a superficial thrombophlebitis: diagnosis of congenital protein C deficiency was possible in the patient as well as in two of his relatives. Two other subjects with congenital protein C deficiency belonging to two different kindreds, whose illness was diagnosed in our center, suffered from myocardial infarction and TIA, respectively, as the only clinical manifestation; a fourth case, previously described, with recurrent superficial thrombophlebitis, suffered from a TIA when on treatment with stanazolol. These cases indicate that arterial thrombosis or TIA is not an uncommon event in congenital protein C deficiency, even in patients without other risk factors for arterial thrombosis.

This is a preview of subscription content, log in to check access.


  1. 1.

    Barbui T, Finazzi G, Mussoni L, Riganti M, Donati MB, Colucci M, Collen D (1984) Hereditary dysfunctional protein C (protein C Bergamo). Lancet 2: 819

  2. 2.

    Bovill EG, Bauer KA, Dickerman JD, Callas P, West B (1989) The clinical spectrum of heterozygous protein C deficiency in a large New England kindred. Blood 73: 712–717

  3. 3.

    Broekmans AW (1985) Hereditary protein C deficiency. Haemostasis 15: 233–240

  4. 4.

    Broekmans AW, Conard J (1988) Hereditary protein C deficiency. In: Bertina RM (ed) Protein C and related proteins. Churchill Livingstone, Edinburgh, pp 160–181

  5. 5.

    Clouse LH, Comp PC (1986) The regulation of haemostasis: the protein C system. N Engl J Med 314: 1298–1304

  6. 6.

    D'Angelo A, Landi G, Viganò D'Angelo S, Nobile-Orazio E, Boccardi E, Candelise L, Mannucci PM (1988) Protein C in acute stroke. Stroke 19: 579–583

  7. 7.

    De Stefano V, Leone G, Teofili L, Ferrelli R, Pollari G, Antonini V, Bizzi B (1988) Transient ischemic attack in a patient with congenital protein C deficiency during treatment with stanazolol. Am J Haematol 29: 120–121

  8. 8.

    De Stefano V, Leone G, Ferrelli R, Hassan HJ, Macioce G, Bizzi B (1988) Factor X Roma: a congenital factor X variant defective at different degrees in the intrinsic and the extrinsic activation. Br J Haematol 69: 387–391

  9. 9.

    De Stefano V, Teofili L, Rocca B, Nicoletti G, Leone G, Bizzi B (1989) Association of congenital protein C deficiency and latent myeloproliferative disease as cause of splanchnic venous thrombosis in a 34-year-old woman. Br J Haematol 73: 565–566

  10. 10.

    De Stefano V, Leone G, Teofili L, Micalizzi P, Netri G, Bizzi B (1990) Mesenteric vein thrombosis in protein S congenital deficiency. Thromb Res 57: 935–944

  11. 11.

    Gandrille S, Priollet P, Capron L, Roncato M, Fiessinger JN, Aiach M (1988) Association of inherited dysfibrinogenaemia and protein C deficiency in two unrelated families. Br J Haematol 68: 329–337

  12. 12.

    Girolami A, Simioni P, Lazzaro AR, Cardiano I (1989) Severe arterial cerebral thrombosis in a patient with protein S deficiency (moderately reduced total and markedly reduced free protein S): a family study. Thromb Haemostas 61: 144–147

  13. 13.

    Gladson CL, Scharrer I, Hach V, Beck KH, Griffin JH (1988) The frequency of type-I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemostas 59: 18–22

  14. 14.

    Griffin JH, Evatt B, Zimmermann TS, Kleiss AJ, Wideman C (1981) Deficiency of protein C in congenital thrombotic state. J Clin Invest 68: 1370–1373

  15. 15.

    Horellou M-H, Conard J, Bertina RM, Samama M (1984) Congenital protein C deficiency and thrombotic disease in nine French families. Br Med J 289: 1285–1287

  16. 16.

    Kannel WB, Thom TJ (1986) Incidence, prevalence, and mortality of cardiovascular diseases. In: Hurst JW (ed) The heart, arteries and veins. McGraw-Hill, New York, pp 557–565

  17. 17.

    Kemkes-Matthes B (1989) Heterozygous protein C deficiency type I. Blut 58: 201–206

  18. 18.

    Leone G, De Stefano V, Di Donfrancesco A, Ferrelli R, Traisci G, Bizzi B (1987) Antithrombin III Pescara: a defective AT III variant with no alterations of plasma-crossed immunoelectrophoresis but with an abnormal crossed immunoelectrofocusing pattern. Br J Haematol 69: 387–391

  19. 19.

    Lugassy G, Klepfish A, Berrebi A (1989) Recurrent thrombophlebitis due to protein C deficiency after splenectomy for immune thrombocytopenic purpura. Acta Haematol 82: 154–155

  20. 20.

    Miletich J, Sherman L, Broze G Jr (1987) Absence of thrombosis in subjects with heterozygous hereditary protein C deficiency. N Engl J Med 317: 991–996

  21. 21.

    Millaire A, Jude B, Petetin N, Marquand A, Watel A, Ducloux G (1988) Maladie thromboembolique veineuse et artérielle familiale par déficit en protéine C J Maladies Vasc 13: 292–293

  22. 22.

    Nelson ME, Talbot JF, Preston FE (1989) Recurrent multiplebranch retinal arteriolar occlusions in a patient with protein C deficiency. Graefe's Arch Clin Exp Ophthalmol 227: 443–447

  23. 23.

    Ødegard OR, Try K, Andersson TR (1987) Protein C: an automated activity assay. Haemostasis 17: 109–113

  24. 24.

    Pabinger I (1986) Clinical relevance of protein C. Blut 53: 63–75

  25. 25.

    Pabinger-Fasching I, Bertina RM, Lechner K, Niessner H, Korninger C (1983) Protein C deficiency in two Austrian families. Thromb Haemostas 50: 810–813

  26. 26.

    Sharon C, Tirindelli MC, Mannucci PM, Tripodi A, Mariani G (1986) Homozygous protein C deficiency with moderately severe clinical symptoms. Thromb Res 41: 483–488

  27. 27.

    Sié P, Boneu B, Biermé R, Wiesel ML, Grunebaum L, Cazenave JP (1989) Arterial thrombosis and protein S deficiency. Thromb Haemostas 62: 1040

  28. 28.

    Smith DB, Ens GE (1987) Protein C deficiency: a cause of amaurosis fugax? J Neurol Neurosurg Psychiatry 50: 361–362

  29. 29.

    Tuddenham EGD, Takase T, Thomas AE, Awidi AS, Madanat FF, Abu Hajir MM, Kernoff PBA, Hoffbrand AV (1989) Homozygous protein C deficiency with delayed onset of symptoms at 7 to 10 months. Thromb Res 53: 475–484

  30. 30.

    Valla D, Denninger MH, Delvigne JM, Rueff B, Benhamou J-P (1988) Portal vein thrombosis with ruptured oesophageal varices as presenting manifestation of hereditary protein C deficiency. Gut 29: 856–859

  31. 31.

    Velasco F, Andres P, Canadillas F, Fornes G, Torres A (1985) Transient ischemic attack (TIA) in a patient with non-thrombogenic hereditary protein C deficiency under oral contraceptives. Thromb Haemostas 54: 904

Download references

Author information

Correspondence to Dr. V. De Stefano.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

De Stefano, V., Leone, G., Micalizzi, P. et al. Arterial thrombosis as clinical manifestation of congenital protein C deficiency. Ann Hematol 62, 180–183 (1991). https://doi.org/10.1007/BF01703145

Download citation

Key words

  • Arterial thrombosis
  • TIA
  • Myocardial infarction
  • Congenital protein C deficiency