Effect of low-molecular weight dextran sulfate on coagulation and platelet function tests.
Low-molecular weight dextran sulfate (DXS 5000, M(r) 5 kDa) was found to control selectively complement activation without affecting contact activation. However, DXS 5000 being a glycosaminoglycan (GAG) may inhibit coagulation, which might bear the risk of bleeding complications and limit its clinical use. We investigated the influence of DXS 5000 on the prothrombin time (PT), the activated partial thromboplastin time (aPTT), the thrombin time (TT), the inhibitory capacity of human plasma against activated factor X (FXa), and on platelet function as assessed by the platelet function analyzer (PFA-100) and by platelet aggregation studies. The PT steadily increased with increasing DXS 5000 concentration, whereas the aPTT was already prolonged (>300 s) at low DXS 5000 concentrations (100 microg/ml). The TT was >120 s at DXS 5000 concentrations of 1000 microg/ml. The inhibitory capacity of human plasma against FXa was dose-dependently increased by DXS 5000. With increasing DXS 5000 concentrations, a prolonged PFA-100 closure time (CT) was observed. Detailed aggregation studies revealed a dose-dependent inhibition of platelet aggregation with ristocetin by DXS 5000, whereas aggregation with ADP, collagen, and arachidonate was unaffected. DXS 5000 induces a disturbance of primary and secondary hemostasis.
Zeerleder
Sacha
S
Central Hematology Laboratory, University of Bern, Inselspital, CH-3010, Bern, Switzerland.
Mauron
Thomas
T
Lämmle
Bernhard
B
Wuillemin
Walter A
WA
D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016264:Dextran Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D016264:Dextran Sulfate