The Relative Frequency of Hereditary Thrombotic Disorders Among 107 Patients with Thrombophilia in Israel

Summary

Since most patients with thrombophilia in Israel are referred for diagnosis to our center, it was possible to estimate the relative frequency of the hereditary disorders leading to thrombophilia. 107 unrelated patients were evaluated over 4 years. Diagnoses were established in 23 patients (21.5%) while in 84 (78.5%) no abnormality was detected. Antithrombin III deficiency was found in 8 patients (7.5%), dominant protein C deficiency in 6 (5.6%), recessive homozygous protein C deficiency in 1, protein S deficiency in 3 (2.8%) and dysfibrinogenemia in 1. Four additional patients (3.7%) had a lupus anticoagulant. The frequency of deep vein thrombosis and pulmonary embolism was similar in patients with and without a definite diagnosis. Thrombosis of visceral or cerebral vessels and a positive family history were more frequent among patients in whom a definite diagnosis was made. In both groups there was a substantial lag between the time of presentation of the first thrombotic episode and the time of evaluation. Since the number of referred patients with thrombophilia has gradually increased over the period of the study, it is at present impossible to establish the prevalence of the various hereditary disorders leading to thrombophilia in the population.

Key words

Thrombophilia - Antithrombin III - Protein C - Protein S - Lupus anticoagulant

• References

• 1 Mannucci PM, Tripodi A. Laboratory screening of inherited thrombotic syndromesl. TTiromb Haemostas 1987; 57: 247-251
• 2 Seligsohn U, Rapaport SI, Zivelin A, Kueffler PR. Extra-adrenal effect of ACTH on fibrinogen synthesis. Am J Physiol 1973; 224: 1172-1179
• 3 Rapaport SI, Zivelin A, Dunelly K. A plasma protein C activity assay suitable for a clinical laboratory. Am J Clin Pathol 1987; 87: 491-497
• 4 Hougie C. Circulating anticoagulants. In: Recent Advances in Blood Coagulation. Poller L. (ed) Churchill Livingstone; Edinburgh: 1985. 4 63-90
• 5 Bishop YM, Frieberg SE, Holland PW. In: Discrete multivariate analysis. MIT Press; Cambridge, MA: 1984. pp 357-364
• 6 Seligsohn U, Berger A, Abend M. et al Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med 1984; 310: 559-562
• 7 Scharrer I, Hach-Wunderle V, Hey land H, Kü hn C. Incidence of defective t-PA release in 158 unrelated young patients with venous thromboembolism in comparison to PC, PS and AT III, fibronogen and plasminogen deficiency. Thromb Haemostas 1987; 58: 72 Abstr
• 8 Briët E, Engesser L, Brommer EJ P, Broekmans AW, Bertina RM. Thrombophilia: Its causes and a rough estimate of its prevalence. Thromb Haemostas 1987; 58: 39 (Abstr)
• 9 Felez J, Rodriguez-Pinto R, Olivier A. et al Multicentric Spanish study of biological causes of deep vein thrombosis. Thromb Haemostas 1987; 58: 72 Abstr
• 10 Mannucci PM, Tripodi A. Diagnostic screening of congenital thrombotic syndromes. Thromb Haemostas 1987; 58: 250 (Abstr)
• 11 Malm J, Laurell M, Nilsson IM, Dahlbäck B. ProteinS and the fibrinolytic system in patients with a history of thrombosis. Thromb Haemostas 1987; 58: 229 (Abstr)
• 12 Grossman B, Duncan A. Prevalence of primary coagulation deficiencies in patients with deep vein thrombosis. Thromb Haemostas 1987; 58: 72 (Abstr)
• 13 Thaler E, Lechner K. Antithrombin III deficiency. Clin Hematol 1981; 10: 369-390
• 14 Michiels JJ, van Vliet HH D M. Hereditary AT III deficiency and venous thrombosis. Neth J Med 1984; 27: 226-231
• 15 Bauer KA, Ashenhurst TB, Chediak J, Rosenberg RD. Antithrombin “Chicago”, a functionally abnormal molecule with increased affinity, causing familial thrombophilia. Blood 1983; 62: 1242-1249
• 16 Epstein DJ, Bergum PW, Bajaj P, Rapaport SI. Radioimmunoassays for protein C and factor X. Am J Clin Pathol 1984; 82: 573-581
• 17 Vigano d’Angelo S, Comp PC, Esmon CT, D’Angelo A. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest 1986; 77: 416-425
• 18 Weiss P, Soff GA, Halkin H, Seligsohn U. Decline of protein C and factors II, VII, IX and during the initiation of warfarin therapy. Thromb Res 1987; 45: 783-790
• 19 Schofield KP, Thomson JM, Poller L. Protein C response to induction and withdrawal of oral anticoagulant therapy. Thromb Haemostas 1987; 58: 131 (Abstr)
• 20 Broekmans AW, Bertina RM, Protein C. In: Recent Advances in Blood Coagulation. Poller L. (ed) Churchill Livingstone; Edinburgh: 1985. 4 117-137
• 21 Pabinger I. Clinical relevance of protein C. Review article. Blut 1986; 53: 63-75
• 22 Comp PC. Hereditary disorders predisposing to thrombosis. In Progress in Hemostasis and Thrombosis. Coller BS. (ed) Grune &Stratton; 1986. 8 71-102
• 23 Wintzen AR, Broekmans AW, Bertina RM. et al Cerebral hemorrhagic infarction in young patients with hereditary protein C deficiency. Evidence for a “spontaneous” cerebral venous thrombosis Br Med J 1985; 290: 350-352
• 24 Broekmans AW, van der Linden IK, Veltkamp JJ, Bertina RM. Prevalence of isolated protein C deficiency in patients with venous thrombotic disease and in the population. Thromb Haemostas 1983; 50: 350 (Abstr)
• 25 Branson HE, Katz I, Marble R, Griffin JH. Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; 2: 1165-1168
• 26 Sills RH, Marlar RA, Montgomery RR. et al Severe homozygous protein C deficiency. J Pediatr 1984; 105: 409-413
• 27 Estellés A, Garcia-Plaza I, Dasi A. et al Severe inherited “homozygous” protein C deficiency in a newborn infant. Thromb Haemostas 1984; 52: 53-56
• 28 Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: A genetic disorder related to the absence of protein C in the blood. Blood 1985; 65: 15-20
• 29 Yuen P, Cheung A, Lin HJ. Purpura fulminans in a Chinese boy with congenital protein C deficiency. Pediatrics 1986; 77: 670-676
• 30 Miletich J, Sherman L, Broze G. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991-996
• 31 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 1525-1528
• 32 Schwartz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297-1300
• 33 Engesser L, Broekmans AW, Briet E, Brommer EJ P, Bertina RM. Hereditary protein S deficiency: Clinical Manifestations. Ann Intern Med 1987; 106: 677-682
• 34 Vermylen J, Blackmans D, Spitz B, Deckmyn H. Thrombosis and immune disorders. Clin Hematol 1986; 15: 393-412
• 35 Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980; 92: 156-159
• 36 Lechner K, Pabinger-Fasching I. Lupus anticoagulant and thrombosis: A study of 25 cases and review of the literature. Haemostasis 1985; 15: 254-262
• 37 Shapiro SS, Thiagarajan P. Lupus anticoagulants. In: Progress in Hemostasis and Thrombosis. Spaet TH. (ed) Grune & Stratton; 1982. 6 263-85
• 38 Exner T, Barber S, Kronenberg H, Rickard KA. Familial association of the lupus anticoagulant. Br J Haematol 1980; 45: 89-96
• 39 Samama M, Horellou MH, Soria J. et al Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemostas 1984; 51: 132-133
• 40 McGehee WG, Klotz TA, Epstein DJ, Rapaport SI. Coumarin necrosis associated with hereditary protein C deficiency. Ann Intern Med 1984; 100: 59-60
• 41 Friedmann KD, Marlar RA, Houston JG, Montgomery RR. Warfarin induced skin necrosis in patients with protein S deficiency. Blood 1986; 68 Suppl (Suppl. 01) 333 (Abstr)
• 42 Friedman KD, Marlar RA, Gill JC, Endres-Brooks J, Montgomery RR. Protein S deficiency in patients with the lupus anticoagulant. Blood 1986; 68 Suppl (Suppl. 01) 333 (Abstr)
• 43 Comp PC, de Bault LE, Esmon NL, Esmon CT. Human thrombomodulin inhibited by IgG from 2 patients with non-specific anticoagulants. Blood 1983; 62 Suppl (Suppl. 01) 299 (Abstr)
• 44 Freyssinet JM, Cazenave JP. Lupus-like anticoagulants, modulation of the protein C pathway and thrombosis. Thromb Haemostas 1987; 58: 679-681
• 45 Bertina RM, van den Linden IK, Engesser L, Muller HP, Brommer EJ P. Hereditary heparin cofactor II deficiency and the risk of development of thrombosis. Thromb Haemostas 1987; 57: 196-200
• 46 Jorgensen M, Bonnevie-Nielsen V. Increased concentration of the fast-acting plasminogen activator inhibitor in plasma associated with familial venous thrombosis. Br J Haematol 1987; 65: 175-180