Activation of Intrinsic Coagulation Pathway in Pre-Eclampsia NOSRATOLA D. VAZIRI, M.D. JULIANNE TOOHEY DAVID POWERS, M.D. KIRK KEEGAN, M.D. ABHA GUPTA, M.D. SHARIAR ALIKHANI MAHIN MASHOOD, M.D. ANTOINE BARBARI, M.D. Irvine, California From the Division of Nephrology and the Uepart- ment of Obstetrics and Gynecology, University of California, Irvine, California. Requests for re- prints should be addressed to Dr. Nosratola D. Vaziri, Department of Medicine, Med Sci I-C351, University of California, Irvine, Califar- nia 92717. Manuscript accepted September 20, 1984. Disseminated intravascular coagulation, thrombocytopenia, consump- tion of factors VIII and II, and antithrombin deficiency have been previously demonstrated in pre-eclampsia. However, the precise mechanism responsible for initiation of dibeminated intravascular coagulation has not been elucidated. The present study documents activation of the Intrinsic coagulation pathway in a patient with severe pre-eclampsia. The studies revealed marked reductions of plasma coagulant activities of all intrinsic pathway factors, i.e., XII, Xl, IX, and VIII. In addition, the ratio of plasma factor XII activity to antigen concentration was markedly abnormal, and plasma high-molecular- weight kininogen concentration was diminished. It is suggested that activation of the intrinsic coagulation pathway may be operatlve in the genesis of disseminated intravascular coagulation in pre-eclampsia. Pre-eclampsia is associated with a variety of coagulation abnormalities. Disseminated intravascular coagulation [l-5], thrombocytopenia [6- 1 I], increased urinary and plasma fibrinogen degradation products [ l-5,12], presence of circulating fibrinopeptide A and beta-thromboglobulin [ 131, increased plasma activities of factors Xl [ 14,151, X, V [ 14,151, and II, and increased plasma fibrinogen concentration [ 16- 181 have been demon- strated in pre-eclampsia. In addition, increased, normal, and reduced levels of factor XII [ 14,191, altered plasma factor XII activity-to-concen- tration ratio, factor VIII consumption [20-251, and antithrombin deficien- cy [26,27] have been reported. The cause-and-effect relationship be- tween pre-eclampsia and the associated coagulation abnormalities and the pathogenesis of the observed coagulopathies have not been elucidat- ed. Although activation of intrinsic coagulation pathway has been pro- posed by some authors [28] as the possible mechanism of disseminated intravascular coagulation in pre-eclampsia, its occurrence has not been previously demonstrated. The present study provides strong evidence for activation of the intrinsic coagulation pathway in a patient with severe pre-eclampsia. CASE REPORT The patient studied was a 30-year-old 31-week pregnant (gravida VII, para V, abortus I) woman who was transferred to the University of California Irvine Medical Center with symptoms of irritability, visual scotomas, and facial and pedal edema. She was found to have severe hypertension (blood pressure = 250/140 mm Hg), facial and lower extremity edema, retinal vasospasm, hyperactive deep tendon reflexes, thick closed cervix with ballotable vertex presentation, and uterine size consistent with the stated length of gestation. No significant uterine contractions were present, and the amniotic sac was intact. She had no history of hypertension prior to or during the first and second trimesters of the current pregnancy or any of the January 1988 The American Journal of Medicine Volume 80 103