Heparin ablates force development during platelet mediated clot retraction.
Although snake venom enzymes such as reptilase do not cause viscous metamorphosis, platelet secretion or clot retraction; when batroxobin and calcium are added to citrated blood significant platelet force development occurs. When this batroxobin-calcium system was applied to the study of platelet function during cardiopulmonary bypass (CPB), force development was found to be completely inhibited. After heparin reversal by protamine sulfate, significant recovery of force occurred. The present investigation was performed to evaluate the role of heparin in reducing force development during CPB. At concentrations above 0.10 U/ml, heparin totally suppressed force development in normal plasma. Addition of protamine sulfate to heparinized plasma caused complete recovery of force development. These concentrations of heparin had little effect on platelet aggregation by ADP or collagen. Possible direct effects of heparin on fibrin assembly and structure were studied by adding varying amounts of heparin to plasma and then inducing clot formation with batroxobin. At 1 U/ml, heparin reduced the size of fibrin fibers by 33%. Higher heparin concentrations had no additional effect. These results indicate that heparin may be responsible for a significant component of the decreased platelet force noted during cardiopulmonary bypass. To test whether heparin's effect could be due to suppression of thrombin activity, the effects of the antithrombin hirudin on force development were measured. Hirudin also inhibited force development in a concentration dependent manner. Thus, heparin's reduction of platelet force development may be due, at least in part, to suppression of thrombin activity.
Carr
M E
ME
Department of Medicine, Medical College of Virginia, Richmond 23298-0230, USA.
Carr
S L
SL
Greilich
P E
PE
D012103:Batroxobin; D001696:Biomechanical Phenomena; D001792:Blood Platelets / Q000502:physiology*; D002315:Cardiopulmonary Bypass; D003018:Clot Retraction; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D011479:Protamines / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011479:Protamines; D006493:Heparin; D012103:Batroxobin