Aspirin resistance, platelet turnover, and diabetic angiopathy: a 2011 update.

In 2004 an editorial article on the so-called "aspirin resistance" and diabetic angiopathy as related to platelet turnover was published by one of us. An update of this issue is now presented. The evidence of an incomplete inhibition of platelet function by aspirin, despite doses of the drug proved to be clinically effective are employed, was first reported in the '80s, in studies devoted to platelet turnover. Based on this concept, the possibility of monitoring the entry of newly formed platelets into the circulation after aspirin ingestion was documented by measuring the return of thromboxane biosynthesis by platelets challenged in vitro by pairs of aggregating agents. The data obtained showed that platelets with intact cyclooxygenase activity could be detected into the circulation of control individuals as early as 4-6hrs after aspirin ingestion, but at shorter time intervals in diabetic angiopathy. In the latter setting, it was concluded that "schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation". As many as 25years after its original publication, the clinical relevance of an accelerated platelet turnover as to "aspirin resistance" has been confirmed and extended to other clinical settings at high risk of ischemic events. Newer aspirin dosing and scheduling, tailored at reducing the individual patient risk related to an incomplete inhibition of platelet function by a standard aspirin dose should now be defined.

Recombinant activated factor VII for hemostatic cover of orthopedic interventions in a girl with thrombocytopenia with absent radii syndrome.

Over the past 10 years recombinant activated factor VIIa (rFVIIa) has been successfully used for treatment and prophylaxis of bleeding in patients with platelet defects, including thrombocytopenia and congenital and acquired platelet function abnormalities. Most reported data concern patients with Glanzmann's thrombasthenia and the information available is still limited, especially for surgery. We report on a 15-year-old girl with thrombocytopenia ( approximately 60,000/microl) and platelet dysfunction (bleeding time 30 min, absent platelet aggregation and ATP secretion in response to collagen), related to thrombocytopenia with absent radii syndrome, undergoing two surgical interventions on the upper limbs due to forearm deformities, with prolonged postoperative revisions. In both surgeries rFVIIa was successfully employed as a bolus administration (80 microg/kg every 4 h during the first day, then every 6 h over the following 5 and 3 days, respectively; tranexamic acid was associated from the second day, administered for 2 weeks), avoiding the need for blood products. This report highlights rFVIIa as an attractive, alternative approach to secure hemostasis in patients with platelet defects; on the other hand, the heterogeneity of reported rFVIIa treatment regimens and, in particular, the lack of definite and easily available parameters (or assays) for monitoring rFVIIa efficacy and safety are the main open issues in this setting.