The physiology of platelet production.

The production of platelets from the bone marrow megakaryocytes is a well-regulated process. Nearly 100 years ago, James Homer Wright described how platelets formed from megakaryocytes and entered the circulation. Subsequent clinical and animal studies have enumerated a number of principles of platelet physiology: the platelet count is constant in any one individual but varies greatly between individuals; an inverse relationship exists between the platelet count and platelet size; the body conserves the mass, not the number, of platelets; and megakaryocyte number, size and ploidy vary in response to changing demands for platelets. With the discovery of thrombopoietin (TPO), a number of additional physiological principles have emerged: TPO takes 24 h to rise maximally and has a maximal half-life of 45 min; TPO levels are inversely and exponentially proportional to the platelet mass; platelets bind and clear TPO from the circulation; and hepatic TPO product on is not altered by changes in the platelet mass. Using these principles, a model for the regulation of platelet production by TPO has been proposed in which the constitutive hepatic TPO produced is removed from the circulation by the platelet mass. Changes in the platelet mass or its ability to clear TPO produce changes in TPO levels resulting in an altered platelet production rate. Using this model, a number of pathological disorders of platelet production, such as essential thrombocythemia and idiopathic thrombocytopenic purpura, are analyzed.