Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions.
A defect in hemostasis has been repeatedly reported in patients with cirrhosis. However, the nature of this defect has not been fully characterized. We explored adhesive and cohesive functions of platelets from cirrhotic patients at different stages of disease development. The response of platelets to standard activating agents was tested by aggregometric procedures. The interaction of platelets with subendothelial components was explored in a perfusion system in which blood was exposed (shear rate, 800/s; 10 minutes) to denuded segments of rabbit aorta. Platelet interactions in these perfusions were analyzed morphometrically. Results were always compared with those obtained in similar studies using blood obtained from healthy subjects. Aggregation studies showed abnormal responses for single or several agonists. Abnormalities in aggregation were more evident in patients with severe disease (Child-Pugh class C), although they occasionally were abnormal for single agonists (ADP or U46619) in patients with less severe disease (Child-Pugh classes A or B). All the patient classes showed impaired platelet-subendothelial interactions (P < .01 vs. healthy subjects) that were not justified by the relative thrombocytopenia present in the more severely affected patients. Experimental increases in hematocrit in patients at stages B and C did not improve platelet-subendothelial interactions. Platelets from cirrhotic patients interact defectively with subendothelial components under flow conditions. The adhesion defect is more evident and consistent than the aggregation defects and may already be present in patients with mild liver failure. This adhesion defect may contribute to the defective hemostasis observed in cirrhotic patients.
Servicio de Hemoterapia y Hemostasia, Hospital Clínic i Provincial, Barcelona, Spain.
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Ordinas
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Escolar
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Cirera
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Viñas
F
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Cobo
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Bosch
J
J
Terés
J
J
Rodés
D000328:Adult; D000368:Aged; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006400:Hematocrit; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D011817:Rabbits
D019038:Platelet Glycoprotein GPIb-IX Complex; D016718:Arachidonic Acid