HEPARIN-INDUCED PLATELET-AGGREGATION .2. DOSE-RESPONSE RELATIONSHIPS FOR 2 LOW-MOLECULAR-WEIGHT HEPARIN FRACTIONS (CY-216 AND CY-222)

We have previously shown that unmodified heparin (bovine lung or porcine mucosal) and a low molecular weight heparin fraction, PK 10169, cause platelet aggregation in a dose and molecular weight-dependent manner. In this report, we show that two other low molecular weight heparin fractions, CY 216 and CY 222, also cause platelet aggregation in a dose and molecular weight-dependent manner. Utilizing heparin and defined fractions of CY 216 and CY 222 separated on the basis of molecular weight, we determined dose/response (D/R) relationships for each of these agents and their individual fractions. In comparison to an unmodified porcine mucosal heparin, CY 216 yielded a D/R curve that was shifted down and to the right, indicating that this agent is less potent in causing platelet aggregation. The D/R curve for CY 222, which has a lower molecular weight that CY 216, was shifted further down and to the right, indicating that it was less potent than CY 216. The D/R curves obtained with the fractions of CY 216 and CY 222 demonstrate that as the molecular weight of the fractions decrease, they become progressively less potent in causing platelet aggregation. Fractions with molecular weights of less than approximately 3,000 daltons are essentially without activity in causing platelet aggregation. Platelet aggregation studies with CY 216 and CY 222 fractions separated on the basis of affinity for antithrombin III (AT III) indicate that the platelet aggregating activity of these agents may not be related to their affinity for AT III. However, these latter results are not conclusive and need to be expanded. © 1990.