Pathogenetic analysis of three cases with a bleeding disorder characterized by defective platelet aggregation induced by Ca2+ ionophores.
We report three cases of platelet dysfunction characterized by defective Ca2+ ionophore-induced platelet aggregation without impaired production of thromboxane A2 (TXA2). The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable TXA2 (STA2) and Ca2+ ionophore A23187 was defective or much reduced. However, ristocetin- or thrombin-induced platelet aggregation was normal. The analysis of second messenger formation showed that inositol 1,4,5-triphosphate formation or Ca2+ mobilization induced by thrombin, STA2 or A23187 was normal. Furthermore, the phosphorylation of 47 kDa protein (pleckstrin) and 20 kDa protein (myosin light chain, MLC) in response to those agonists was normal. These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca2+ mobilization and MLC phosphorylation.
Fuse
I
I
First Department of Internal Medicine, Niigata University School of Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan. fuse@med.niigata-u.ac.jp
Higuchi
W
W
Uesugi
Y
Y
Aizawa
Y
Y
D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000328:Adult; D016718:Arachidonic Acid; D001791:Blood Platelet Disorders / Q000175:diagnosis* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D000001:Calcimycin; D002118:Calcium / Q000378:metabolism*; D003094:Collagen; D005260:Female; D006801:Humans; D007476:Ionophores; D008297:Male; D008875:Middle Aged; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D012310:Ristocetin; D013917:Thrombin; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000032:analysis
D001798:Blood Proteins; D007476:Ionophores; D018994:Myosin Light Chains; D010750:Phosphoproteins; D010980:Platelet Membrane Glycoproteins; C039077:platelet protein P47; D012310:Ristocetin; D016718:Arachidonic Acid; D000001:Calcimycin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C037866:STA 2; D000255:Adenosine Triphosphate; D003094:Collagen; D013917:Thrombin; D002118:Calcium