164 CHLORPROMAZINE AND PLATELET FUNCTION
SiR,—There is considerable evidence that a high proportion of thrombi in arteries are formed from aggregated platelets’I through the activation of circulating platelets by adenosine diphosphate (A.D.P).2 One possible source of A.D.P. is the platelets themselves after their initial adherence to collagen or to other subendothelial structures.3,4 Another, possibly much more important, source is the red cells which outnumber and surround the platelets in the bldod and which contain A.D.P. in
high concentrations. Born et al.5 suggested that A.D.P. leaks from intact, metabolically normal erythrocytes during reversible deformations imposed on the cells by hxmodynamic stresses in diseased and narrowed arteries. This was based on the observation that such as chlorpromazine, which stabilise erythrocyte membranes against haemolysis,6 in concentrations below those which affect platelets directly,’ prolong bleeding-time from an artificial vessel by decelerating the formation of platelet plugs. We have found that small doses of chlorpromazine cause significant prolongation of the bleeding-time in apparently healthy individuals, but no change in in-vitro platelet-function
drugs
This effect was not due to inhibition of platelet release because the chlorpromazine concentration required for such an inhibition in vitro (8 umol/1) is a hundred times greater than the maximum plasma concentration achieved after injection of the biggest dose (20 mg)." Probably most of the drug is rapidly removed into the tissues.’2 These plasma concentrations are also much lower than those which affect platelet aggregation directly.’ The most likely explanation of the increase in bleeding-time is, as suggested by Born et al,5 a decrease in the haemostatic efficacy of the platelets through an action of chlorpromazine on the red blood-cells, possibly by diminishing the leakage of A.D.P. from them. The observation also supports the propositions that drugs which, like chlorpromazine stabilise red-cell membranes may represent a novel approach to the prevention of arterial thrombosis. Department of Medicine B, Ichilov Hospital and Tel-Aviv University School of Medicine, Tel-Aviv, Israel *
Present address: Thrombosis Research School, London SE5 8RX.
J. ZAHAVI* G. SCHWARTZ
Unit,,King’s College Hospital
Medical
tests.
Bleeding-time (modified Ivy method8) platelet-count, 5-hydroxytryptamine content of platelets9 and platelet aggregation 10 in platelet-rich plasma induced by A.D.P. 0.6 and 4 p.mol/1, colBLEEDING-TIME
(min)
BEFORE AND AFTER INTRAMUSCULAR
CHLORPROMAZINE
Results as mean + s.E.M. Bleeding-times significantly prolonged for all three chlorpromazine doses at P
SiR,—There is considerable evidence that a high proportion of thrombi in arteries are formed from aggregated platelets’I through the activation of circulating platelets by adenosine diphosphate (A.D.P).2 One possible source of A.D.P. is the platelets themselves after their initial adherence to collagen or to other subendothelial structures.3,4 Another, possibly much more important, source is the red cells which outnumber and surround the platelets in the bldod and which contain A.D.P. in
high concentrations. Born et al.5 suggested that A.D.P. leaks from intact, metabolically normal erythrocytes during reversible deformations imposed on the cells by hxmodynamic stresses in diseased and narrowed arteries. This was based on the observation that such as chlorpromazine, which stabilise erythrocyte membranes against haemolysis,6 in concentrations below those which affect platelets directly,’ prolong bleeding-time from an artificial vessel by decelerating the formation of platelet plugs. We have found that small doses of chlorpromazine cause significant prolongation of the bleeding-time in apparently healthy individuals, but no change in in-vitro platelet-function
drugs
This effect was not due to inhibition of platelet release because the chlorpromazine concentration required for such an inhibition in vitro (8 umol/1) is a hundred times greater than the maximum plasma concentration achieved after injection of the biggest dose (20 mg)." Probably most of the drug is rapidly removed into the tissues.’2 These plasma concentrations are also much lower than those which affect platelet aggregation directly.’ The most likely explanation of the increase in bleeding-time is, as suggested by Born et al,5 a decrease in the haemostatic efficacy of the platelets through an action of chlorpromazine on the red blood-cells, possibly by diminishing the leakage of A.D.P. from them. The observation also supports the propositions that drugs which, like chlorpromazine stabilise red-cell membranes may represent a novel approach to the prevention of arterial thrombosis. Department of Medicine B, Ichilov Hospital and Tel-Aviv University School of Medicine, Tel-Aviv, Israel *
Present address: Thrombosis Research School, London SE5 8RX.
J. ZAHAVI* G. SCHWARTZ
Unit,,King’s College Hospital
Medical
tests.
Bleeding-time (modified Ivy method8) platelet-count, 5-hydroxytryptamine content of platelets9 and platelet aggregation 10 in platelet-rich plasma induced by A.D.P. 0.6 and 4 p.mol/1, colBLEEDING-TIME
(min)
BEFORE AND AFTER INTRAMUSCULAR
CHLORPROMAZINE
Results as mean + s.E.M. Bleeding-times significantly prolonged for all three chlorpromazine doses at P
