Chantal Lecrubier

In vitro aspirin resistance detected by PFA‐100TM closure time: pivotal role of plasma von Willebrand factor

The in vitro closure time (CT), determined by the Platelet Function Analyzer (PFA‐100TM), is used to monitor patients treated with aspirin. A relatively high percentage of in vitro aspirin resistance was reported despite an adequate inhibition of platelet response to arachidonic acid and we investigated whether high plasma levels of von Willebrand factor ristocetin cofactor activity (vWF:RCo) may contribute to this profile. Platelet aggregation test, CT [collagen adrenaline (CEPI‐CT) and collagen adenosine 5′‐diphosphate (ADP) (CADP‐CT)], and vWF:RCo levels were evaluated in 55 consecutive patients receiving aspirin (75–250 mg/d) versus 32 untreated control subjects. All the aspirin‐treated patients showed platelet aggregation responses that reflected the aspirin intake. However, CT data analysis enabled aspirin good‐responder (GR) and aspirin bad‐responder (BR) patients to be identified. All GR group subjects (n = 27), had a CEPI‐CT and a CADP‐CT longer than 300 s and 96 s respectively. The BR group (n = 28) had CEPI‐CT values below 200 s and all CADP‐CT were in the normal range (77 ± 19 s). Interestingly, the BR plasma vWF:RCo levels were significantly higher (159 ± 43%) than those of the GR group (121 ± 34%) (P < 0·01), which were similar to control values (114 ± 31%). A negative correlation between vWF:RCo and CT values was established. We demonstrate that in vitro aspirin‐resistance, revealed by PFA‐100TM CT prolongation failure, is correlated to increased plasmatic vWF:RCo levels, reinforcing its particular importance in PFA‐100TM cartridges performance.

Reticulated platelets: a reliable measure to reduce prophylactic platelet transfusions after intensive chemotherapy

BACKGROUND: Reticulated platelets (RPs) are the youngest circulating platelets (PLTs). The aim of our study was to predict PLT recovery with RP percentage (RP%) and therefore to identify PLT transfusions that could be avoided after autologous peripheral blood progenitor cell (PBPC) transplantation.

Antiplatelet Effects of the Addition of Acetylsalicylic Acid 40 Mg Daily to Ticlopidine in Human Healthy Volunteers

Clinical studies have shown that acetylsalicylic acid (ASA) or ticlopidine (T) bring a partial clinical benefit in a subset of patients threatened by thrombosis on atherosclerotic plaques. Acetylsalicylic acid and T have different impacts on platelet function and the combination of the drugs seems logical to achieve a greater antiplatelet effect. Healthy volunteers were randomly allocated to any of the three treatment groups: T 250-placebo; T 250-T 250; placebo-placebo (treatment was administered in a double blind manner). Acetylsalicylic acid 40 mg was openly administered once a day to the subjects of the three groups after the first week of treatment. Simplate I bleeding time and platelet aggregation testing were performed before treatment and at the end of the two treatment periods. We confirmed that T alone prolongs bleeding time and impairs, in a dose-dependent manner, ADP-induced aggregation; platelet responses that depend on released ADP were also affected. Inhibition of thromboxane-dependent aggregation, associated with a doubling of the bleeding time, was observed after one week of low-dose ASA inhibition of thromboxane synthesis. An additive effect of ASA 40 mg to T 250 mg on the bleeding time was evidenced. There was also a wider alteration of platelet aggregation, with a trend towards an inhibition of the response to a high concentration of collagen as compared to ASA or T used alone. Such a powerful, logical drug combination is in good agreement with preliminary encouraging results obtained after coronary stent implantation and deserves further studies in patients at high risk for arterial thrombosis to define its benefit-risk profile. Key Words: Aspirin—Ticlopidine— Drug combination—Bleeding time—Platelet aggregation.

INCREASED SENSITIVITY OF PLATELETS TO ADRENALINE IN HUMAN MYOTONIC DYSTROPHY

Platelets from patients with myotonic dystrophy showed a normal pattern of aggregation in response to adenosine diphosphate (A.D.P.) and collagen but were unusually sensitive to adrenaline, aggregation being detectable with adrenaline concentrations as low as 0.041 mumol per litre. In other diseases in which such sensitivity has been reported this has been accompanied by a similarly altered response to A.D.P. The increased platelet aggregation could be due to increased uptake of Ca++ by platelets or to a decrease in phosphorylation of the platelet membrane.

ABNORMAL FACTOR-VIII-RELATED ANTIGEN, VON WILLEBRAND DISEASE, AND PREGNANCY

S!R,&mdash;Professor Caen and Dr Sultan’ suggest that von Willebrand disease is primarily a vascular defect, located mainly in the endothelial cells. This hypothesis has brought to our mind a patient we have been studying for several years. This woman has: a bleeding-time (Duke’s method) permanently longer than 15 min; factor-vin activity 25%; factor-v III-related antigen <10%; no platelet aggregation by ristocetin (1-3 5 mg/ml final concentration); and von Willebrand factor (Weiss) 10%. Her three children, from three different fathers, all have the