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On page 23, it is stated that direct thrombin inhibitors do not require monitoring; however, they do. Argatroban, lepirudin, and hirudin all must be closely monitored by partial thromboplastin time (PTT) as often as every 2 hours to ensure appropriate dosing. With argatroban, PTT should be checked 2 hours after initiation of the infusion, and 2 hours after any change, then can be decreased to twice daily if at goal range. For lepirudin and hirudin, PTT should be checked 4 hours after initiation or change, then can be decreased to daily if at goal range. Also, because argatroban is cleared hepatically, the starting infusion rate should be lower than the 2.0 µg/kg/min noted if there is any hepatic impairment.
Lepirudin and hirudin are cleared renally and dose adjustments are also necessary. Bivalirudin (more commonly used during percutaneous interventions) should have associated activated clotting time monitoring, if there is any renal impairment.
The issue of thrombocytopenia resulting from use of some glycoprotein IIb-IIIa receptor inhibitors is reviewed; however, it is not noted that a baseline platelet count of under 100000 is a contraindication to using any of these agents. It is also stated (page 24) that eptifibitide "has not been associated with increased rates of thrombocytopenia vs placebo," with reference given to the PURSUIT trial experience in 1999.1 While realizing that the article was written in 2004, a review of more recent references since 1999 would have been helpful to show how more recent clinical experiences have added to the side effect profile of the drug. Although thrombocytopenia appears to be less common with eptifibatide, there have been several reports of severe thrombocytopenia associated with eptifibatide,2–5 and myself and my colleagues have experienced this clinically many times as well.
References
The comments about the need for monitoring of direct thrombin inhibitors and the contraindication to use of glycoprotein IIb-IIIa inhibitors in patients with a platelet count of less than 100000/mL are valid and accurate, and I thank Ms Chevoya for this clarification.
As for the lack of increase in thrombocytopenia with eptifibatide versus placebo, the prescribing information for INTEGRILIN (eptifibatide) states that the rates of thrombocytopenia in the PURSUIT trial with eptifibatide and placebo were similar. As reported by McClure and colleagues,1the rates of thrombocytopenia (defined as platelet count<100000/mL or <50% of baseline) in the PURSUIT trial were 7% (319/4603) in the placebo group and 6.9% (314/4614) in the eptifibatide group, demonstrating that eptifibatide is not associated with increased incidence of thrombocytopenia versus placebo. Randomized, placebo-controlled clinical trials, such as PURSUIT, provide the most reliable scientific evidence regarding the prevalence of relatively infrequent events, such as thrombocytopenia, while also allowing the comparison of individual event rates with the active drug versus placebo. Although individual cases of severe thrombocytopenia in patients receiving eptifibatide have been reported in the literature, as noted by Ms Chevoya, it is unclear whether thrombocytopenia is directly related to the use of this drug in these cases. Additionally, these case reports do not have a control group, in contrast to randomized, placebo-controlled trials. Finally, treatment with eptifibatide, including readministration within 28 days, has not been associated with development of antibodies to eptifibatide (as described in the INTEGRILIN prescribing information), a finding that is consistent with the absence of increased thrombocytopenia with eptifibatide versus placebo in the PURSUIT trial. Therefore, in my opinion, the statement "eptifibatide has not been associated with increased rates of thrombocytopenia vs placebo" is still accurate and valid.
Reference
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