This study describes a laboratory model of whole blood (WB) thrombocytopenia established with blood from healthy volunteers. We obtained a mean platelet count of 16 × 109/l (95% confidence interval, 10-22) in WB by repeatedly replacing the platelet-rich supernatant with autologous platelet-poor plasma from the same individual. Thrombelastographic profiles of WB clot formation and WB clot stability were performed in parallel with measurements of WB platelet aggregation response. Thrombocytopenia reduced the maximum rate of WB clot formation, while ex vivo addition of platelets reversed the coagulopathy of thrombocytopenia. Control experiments revealed minimal changes in coagulation factors, distribution of bloods cells, and platelet activation capabilities. The WB model appears useful in research, development, and evaluation of the effects of hemostatic interventions in thrombocytopenia.