Heparin-neutralizing activity in the plasma of women with gynecologic malignancy: the effect of tumor stage on heparin concentration and fibrin generation after low-dose heparin.
The relationship between tumor stage and the concentration of circulating heparin achieved after subcutaneous administration and its effect on fibrin generation were studied in 24 women with gynecologic malignancy. A single subcutaneous injection of 5000, 7500, and 10,000/U of sodium heparin was given in random order on different days. Plasma specimens for antithrombin III, fibrinopeptide A, and heparin were obtained serially over an 11-hour interval. Women with a Stage III or IV malignancy had significantly lower circulating heparin after the 5000 and 10,000/U doses. There was a significant decline in fibrinopeptide A as the concentration of circulating heparin increased. Thirty-three percent of women with a Stage III or IV malignancy had no detectable circulating heparin at any point examined over the 11 hours after 5000/U of heparin. Likewise, 16.7% and 8.4% had no detectable circulating heparin after 7500 and 10,000/U, respectively. A similar percentage was noted in a smaller group of women with Stage II malignancy. Next, a known quantity of heparin was added to the plasma from these patients and the concentration of heparin was determined. A significant amount of heparin-neutralizing activity was documented. We conclude that a large percentage of women with an advanced gynecologic malignancy are able to neutralize heparin administered for the prevention of thromboembolic disease. This heparin-neutralizing activity may account for the failure of low-dose heparin to prevent thromboembolic complications in this patient population.
D000990:Antithrombin III / Q000032:analysis; D005260:Female; D005337:Fibrin / Q000032:analysis*; D005344:Fibrinopeptide A / Q000032:analysis; D005833:Genital Neoplasms, Female / Q000097:blood* / Q000150:complications; D006493:Heparin / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D013923:Thromboembolism / Q000517:prevention & control
D005344:Fibrinopeptide A; D000990:Antithrombin III; D005337:Fibrin; D006493:Heparin