Platelet dysfunction and inhibition of multiple electrode platelet aggregometry caused by penicillin

Inhibition of platelet function in the presence of beta-lactam antibiotics was first described decades ago. In the first documented report in 1973, Cazenave et al. found that beta-lactam antibiotics (BLA), e.g. penicillin, inhibit all major types of platelet functions in vitro, such as secretion, adhesion and also aggregation [1]. Postulated mechanisms are inhibition of agonist-stimulated platelet calcium influx [2], and impairment of agonist binding to their specific receptors on the platelet surface [3]. Importantly, penicillin binds irreversibly to platelets [4]. This results in a dose- and time-dependent effect of BLA on platelet function in animals and humans, which occurs within 24 to 72 hours after therapy induction [4-6].A 46-year old female patient presented to our clinic with a perimandibular abscess following surgical removal of a third molar. The patient had no medical therapy upon admission. Despite elevated inflammation parameters other blood tests were normal. The patient was treated with surgical drainage and intravenous penicillin (12 million IU/day) because of local infection with penicillin-sensitive streptococcus species. Due to swelling of the neck and jaw the patient required mechanical ventilation for three days. In addition to antibiotic therapy, the patient received fentanyl and midazolam intravenously for analgo-sedation, and enteral feeding by tube.On postoperative day 3 bleeding tendency during invasive procedure (routine placement of arterial catheter) was noticed. Platelet counts (174000 [150000-450000]/μl), partial thromboplastin time (PTT 31 [25-39] sec) and international normalized ratio (INR 1.0) were normal. However, multiple electrode platelet aggregometry (MEA)[7] revealed significant inhibition in platelet function in both adenosine diphosphate (ADP) and arachidonic acid (AA) tests (fig. 1). In detail, on day 3 MEA area under the curve (AUC) in response to ADP was 250, and 109 in response to AA respectively. In a recent study, M