title: The in-vitro and ex-vivo effects of chloroquine sulphate on platelet function: implications for malaria prophylaxis in patients with impaired haemostasis.
abstract: Platelet aggregation responses were studied in platelet-rich plasma from six healthy volunteers before and 2 and 6 h after ingestion of 600 mg chloroquine sulphate. Apart from a mild reduction in height of aggregation response to 1 microgram ml-1 collagen 2 h post-drug ingestion (mean percentage of pre-drug values +/- s.e.m. = 87.8% +/- 4.0%; P = 0.04), no significant differences were observed in platelet responses to ADP (1 and 5 microM) or collagen (1 and 4 micrograms ml-1) at 2 or 6 h post-chloroquine compared to the pre-drug values. In vitro, drug concentrations approximately 1000 times greater than those used therapeutically were required for 50% inhibition of platelet aggregation and ATP release in response to 5 microM ADP, 1 microgram ml-1 collagen and 4 micrograms ml-1 collagen (IC50 concentrations +/- s.e.m. for inhibition of aggregation = 98.5 +/- 3.7, 53.5 +/- 56.4 and 113.0 +/- 6.2 mg l-1 respectively; IC50s +/- s.e.m. for inhibition of ATP release = 0.9 +/- 0.2, 14.7 +/- 4.0 and 23.0 +/- 5.3 mg l-1 respectively). These data provide no cause for concern in using chloroquine for malaria prophylaxis in patients with impaired haemostasis.
authors.affiliation: Department of Haematology, University College and Middlesex School of Medicine, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cummins
authors.forename: R
authors.initials: R
authors.lastname: Faint
authors.forename: D A
authors.initials: DA
authors.lastname: Yardumian
authors.forename: S
authors.initials: S
authors.lastname: Dawling
authors.forename: I
authors.initials: I
authors.lastname: Mackie
authors.forename: S J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D001778:Blood Coagulation Disorders / Q000150:complications; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008288:Malaria / Q000150:complications / Q000517:prevention & control; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*
chemical_list: D000244:Adenosine Diphosphate; D002738:Chloroquine; D000255:Adenosine Triphosphate; D003094:Collagen