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  • Title: Heparin cofactor II activity in plasma during pregnancy and oral contraceptive use.
    Author: Massouh M, Jatoi A, Gordon EM, Ratnoff OD.
    Journal: J Lab Clin Med; 1989 Dec; 114(6):697-9. PubMed ID: 2592856.
    Abstract:
    Inhibition of thrombin by heparin is mediated by at least two plasma proteins, antithrombin III, and heparin cofactor II. The plasma titer of heparin cofactor II was significantly elevated in both pregnant women and users of oral contraceptives. During pregnancy, changes in hemostatic mechanisms occur: the plasma concentration of fibrinogen and the titers of Hageman factor (factor XII), antihemophilic factor (factor VIII), and von Willebrand factor (vWf) increase dramatically. Freshly prepared plasmas from 15 women aged 22-35 who were not using oral contraceptives (OCs), from 10 women of the same age who were using OCs, and from 15 pregnant women (6 in the 2nd trimester and 9 in the 3rd trimester) were tested. In addition, the plasmas of 15 women (stored at minus 70 degrees Celsius for as long as 2 years) were tested from blood drain before and from 3 weeks to 1 year after commencing the use of OCs (20-40 mcg of ethinyl estradiol and 1-1.5 mg of norethindrone). 24 plasmas from men aged 21-40 years was also prepared. This pool was arbitrarily said to contain 1 U/ml of heparin cofactor II. An increase in the titer of hearing cofactor II was observed in fresh plasma samples of pregnant women compared with age-matched nonpregnant women. The effect of OC use on the plasma titer of heparin cofactor II was assessed in 2 groups of women. Measured in fresh plasma, the titer of heparin cofactor II was elevated by an average of 40% in OC users compared with age-matched controls. In another study, OC usage increased the titer of hearing cofactor II by an average of 38% when plasma was obtained before and from 3 weeks to 1 year after starting OC use so that each women served as her own control. The absolute titers of these plasmas appeared to be about 1/5 lower than those of freshly tested plasmas. Estrogens, but not progestogens, increase the titer of Hageman factor in rats. A similar effect was noted upon administration of prolactin to hypophysectomized, ovariectomized rats. Whether the increased titer of heparin cofactor II is mediated by estrogens or prolactin is yet to be determined. The biological significance of the increased titer of heparin cofactor II in pregnant women and women using OCs is not clear.
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