Heparin therapy leads to platelet activation and prolongation of PFA-100 closure time.
BACKGROUND
Heparin is used in the treatment of venous and arterial thromboembolic events, including unstable angina. Once unfractionated heparin is discontinued during the acute phase of unstable angina, it has been demonstrated that the disease process may be reactivated within hours. It is hypothesized that this reactivation may be a result of direct platelet activation by heparin that can linger even after the drug itself has been stopped. Prior studies have shown that heparin can either increase or decrease platelet activation. More recent studies have also shown conflicting effects of unfractionated heparin on PFA-100 testing.


METHODS
We studied the in-vitro effects of unfractionated heparin on platelet function and PFA-100 testing. Unfractionated heparin was incubated with whole blood taken from 18 healthy volunteers. Platelet activation and aggregation was assessed with and without the presence of heparin.


RESULTS
Platelet aggregation and activation were increased in the presence of heparin. Unfractionated heparin also significantly prolonged collagen/adenosine diphosphate closure time but did not affect collagen/epinephrine closure time.


CONCLUSIONS
Unfractionated heparin leads to direct platelet activation and increases platelet aggregation in vitro. Unfractionated heparin causes prolongation of the collagen/adenosine diphosphate closure time in PFA-100 testing, possibly as a result of direct binding to von Willebrand factor in solution and interference with von Willebrand factor-glycoprotein Ib binding.
Williams
Marlene S
MS
Department of Medicine, Johns Hopkins Medical Institute, Baltimore, MD, USA mswillia@jhmi.edu
Ng'alla
Ladina S
LS
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010974:Platelet Aggregation; D010976:Platelet Count; D010979:Platelet Function Tests; D013997:Time Factors
D000925:Anticoagulants; D006493:Heparin