Platelet aggregation and chlorpromazine therapy.

The reliability of 5‐hydroxytryptamine induced platelet aggregation responses in schizophrenic patients treated with neuroleptic drugs.

“…Of the various possibilities tested, only dilution of platelet rich plasma proved to be a significant factor in that a relatively minor dilution led to enhanced responses becoming non-enhanced. We validated this finding in our re-examination of a group of chronic schizophrenic patients receiving chlorpromazine, in whom enhanced responses could be elicited more readily if blood samples were centrifuged at a slower speed during the preparation of PRP, and we believe that over-centrifugation may account, at least in part, for the low incidence of enhanced aggregation responses in this group of patients reported by Boullin et al (1978). There is no obvious reason why dilution of PRP should have these effects, as it has been shown by Boullin, Grahame-Smith & Grimes (1975b) that enhanced aggregation is due to a change in the properties of platelets themselves rather than to any factor in the plasma, and one would therefore have expected abnormal or enhanced responses irrespective of the number of platelets in the sample.…”

“…We have recently reported (Orr, Knox, Allen, Gelder & Grahame-Smith, 1981) a series of clinical studies in which we have shown that enhanced platelet aggregation responses in psychiatric patients receiving a variety of neuroleptic drugs do not occur as consistently or as often as expected from previous work (Boullin, Woods, Grimes, Grahame-Smith, Wiles, Gelder & Kolakowska, 1975;Boullin, Knox, Peters, Orr, Gelder & Grahame-Smith, 1978). We have shown that our previous findings with chlorpromazine do not generalise readily to other neuroleptic drugs, and that some patients show considerable variability in platelet aggregation responses.…”

“…The effects of dilution are presumably due to a decrease in the number of platelets in the sample of PRP, and this can also be achieved by over-centrifugation of blood samples during preparation of PRP. Boullin et al (1978) reported platelet aggregation enhancement in only two of thirteen chronic schizophrenic patients receiving chlorpromazine; on examination of the techniques followed we found that blood samples were centrifuged at 180-200 g during preparation of PRP, and this could have led to a decrease in the number ofplatelets in PRP. We therefore re-tested twelve of the thirteen patients on a separate occasion and showed that, if blood samples were centrifuged at 100 g, the frequency with which enhanced responses could be observed increased so that half the patients now showed enhanced aggregation.…”

Increased platelet membrane [3H]‐LSD binding in patients on chronic neuroleptic treatment.

“…Several attempts to replicate these findings were only partially successful. In one study only two of 13 patients showed enhanced aggregation (Boullin et al, 1978b). In other groups individual aggregation responses varied considerably from week to week, and often showed poor correlations with clinical state .…”

Drug-Induced Thrombosis—Experimental, Clinical, and Mechanistic Considerations

“…Due to this immediate effect, the risk of thrombosis may be increased in SSRItreated patients (Kurne et al, 2004). Enhanced platelet aggregation induced by serotonin has also been demonstrated in patients with schizophrenia treated with chlorpromazine (Boullin et al, 1975a(Boullin et al, , 1975bOrr and Boullin, 1976;Boullin et al, 1978;Orr et al, 1981), fluphenazine (Orr and Boullin, 1976;Orr et al, 1981), flupenthixole (Orr et al, 1981), trifluoperazine (Orr et al, 1981), and haloperidol (Orr et al, 1981). However, the suggested increase of platelet aggregation induced by antipsychotics has never been associated with clinical cases of venous thromboembolism (Hagg and Spigset, 2002).…”