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40 HEREDITARY THROMBOPHILIAS MEDIATING ARTERIAL THROMBOTIC EVENTS.
  1. Q. Khalil,
  2. D. Aregawi,
  3. M. Winiarska,
  4. M. Agloria,
  5. J. Munjal,
  6. M. Haque,
  7. P. Wang,
  8. C. J. Glueck.
  1. Cholesterol Center, Jewish Hospital, Cincinnati, OH

Abstract

In 10 normolipidemic patients with 1 or more myocardial infarctions (MI) < age 45, 8 of whom had MI < age 35 years, we speculated that hereditary thrombophilias promoted arterial thrombosis. Thrombophilias studied by PCR included G1691A factor V Leiden, G20210A prothrombin, MTHFR C677T-A1298C, and platelet glycoprotein PL A1/A2 mutations, with serologic studies of ACLA IgG and IgM, the lupus anticoagulant, proteins C, S, and antithrombin III, homocysteine, and factors VIII and XI. Hypofibrinolysis studies included the 4G4G plasminogen activator inhibitor 1 mutation, plasminogen activator inhibitor activity (PAI-Fx), and Lp(a). Cases were compared to healthy normal controls (239 for PCR, 75 for serologic measures). At study entry, without diet-pharmacotherapy, 10 normolipidemic patients with one or more MI < 45 were selected by LDL cholesterol (LDLC) < 130 mg/dL, HDL cholesterol (HDLC) > 35 in men and > 40 mg/dL in women, and triglycerides (TG) < 200 mg/dL. In these 10 normolipidemic patients (7 men, 3 women, 9 white, 1 black, 1 smoker, 2 diabetic), mean ± SD age was 46 ± 13, BMI 26.0 ± 2.8, LDLC 90 ± 31, HDLC 49 ± 10, and TG 93 ± 35 mg/dL. Factor V Leiden heterozygosity was present in 2 of 10 (20%) cases vs 8 of 239 (3%) controls (p = .055). High factor VIII (> 150%) was present in 4 of 7 (57%) cases vs 0/36 controls (p = .0003). Of 14 hyperlipidemic patients having an arterial event < age 45 (6 MI, 1 coronary artery bypass graft, 1 angioplasty, 2 ischemic stroke, 4 TIA), 8 men, 6 women, 12 white, 2 other, 6 smokers, 3 diabetic, 1 smoker and diabetic, mean ± SD age was 40 ± 8, BMI 31.3 ± 6.5, LDLC 105 ± 42, HDLC 38 ± 9, and TG 243 ± 203 mg/dL. Four of these 14 cases (29%) had high factor VIII (> 150%) vs 0/36 controls (p = .004), 2 of 11 (18%) had high factor XI (> 150%) vs 0/61 controls (p = .022), and 5 of 13 (38%) had hypofibrinolytic high PAI-Fx (> 21.1 U/mL) vs 4/61 (7%) controls (p = .007). In both normo- and hyperlipidemic patients sustaining an arterial thrombotic event before age 45, and especially before age 35, we speculate that heritable thrombophilias (factors VIII, XI, factor V Leiden) or hypofibrinolysis (PAI-Fx) may contribute to endothelial damage or altered hemostatic equilibrium and thus promote arterial thrombotic events. In patients with thrombophilia and/or hypofibrinolysis-mediated arterial thrombotic events before age 45, we speculate that thromboprophylaxis might have value in secondary prevention of subsequent arterial thrombotic events.

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