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About the Authors:
Ted S. Strom
* E-mail: [email protected]
Affiliations Department of Pathology and Laboratory Medicine, Memphis Veterans Administration Medical Center, Memphis, Tennessee, United States of America, Department of Pathology and Laboratory Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee, United States of America
Introduction
Accelerated platelet consumption rates are thought to underlie multiple types of thrombocytopenia, including immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), heparin induced thrombocytopenia (HIT), and disseminated intravascular coagulation (DIC). No current diagnostic test, however, is capable of directly distinguishing thrombocytopenias due to rapid platelet clearance from those due to impaired platelet production. A major stumbling block in this area is the lack of a mathematical model capable of simultaneously quantifying the effect of changes in random platelet consumption processes, and lifespan-dependent platelet consumption, from net in vivo platelet consumption data. Such a model would also allow inference of the platelet population turnover rate (i.e. the platelet production rate), and would allow the interpretation of data obtained with allogeneic as well as autologous platelets.
Random platelet consumption occurs in association with hemostasis, but can also occur due to uptake by splenic macrophages, hepatic macrophages (Kupffer cells), or hepatocytes [1]. Lifespan dependent platelet consumption is mediated by a platelet intrinsic process that terminates in apoptosis [2]. Efforts to quantify the sum of these two types of process typically involve ex vivo labeling of platelets with a radioisotope (such as 111Indium) or a fluorescent marker (such as CMFDA), injecting them into a recipient, and following the rate at which they are cleared from the circulation. Alternatively, platelets can be labeled in vivo by injection of sulfo-NHS-biotin, and their clearance can again be followed over time. For both types of study, the resultant curves would be linear if age-dependent clearance predominated, or exponential if random clearance predominated. They are a hybrid of the two in most circumstances [3], [4], [5], [6], [7], and quantifying the contributions of the two types of process is problematic.
The Mills-Dornhorst equation [8]–[9],originally intended to model red cell survival, has been used to interpret in vivo platelet consumption data. It is:(1)Applied to platelet consumption, the terms of the equation can be described as follows: N0 is the number of platelets in a circulating population at time zero;...