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Decreased platelet survival and function have been observed in patients with chronic hypoxemia. To develop a model for investigating these problems, we have studied the mouse exposed to severe hypobaric hypoxia. Mice were exposed to 0.3 or 0.4 atmospheres (ATM) of hypobaric hypoxia 16-19 hours daily for 18 days. Platelet counts first increased with a peak of 1.5 times baseline on day 3 followed by a decline below baseline during the second week of exposure. The greatest effect occurred at 0.3 ATM with a decline of platelets to 15% of baseline as compared to a nadir of 50-80% of baseline at 0.4 ATM. Survival of 51Cr- labeled platelets from untreated donors infused on day 13 of hypoxic exposure was decreased to 1/2 of control in the 0.3 ATM group but normal in the 0.4 ATM group. Megakaryocyte concentration showed the same trend with a decrease to 1/2 of control at 0.3 ATM with only a slight decrease at 0.4 ATM. Platelet aggregation with ADP was markedly reduced after two weeks exposure to 0.3 ATM. Aggregation of control platelets suspended in plasma from the 0.3 ATM group was depressed. Aggregation of control platelets resuspended in equal volumes of hypoxic and control plasmas was also decreased. Resuspension of control platelets in control plasma after a 1 hour incubation with hypoxic plasma partially restored the platelet aggregating activity. These studies indicate that exposure of mice to 0.3 ATM of hypobaric hypoxia for two weeks produces thrombocytopenia and decreased platelet aggregation. The decrease in platelet count is associated with decreased platelet survival and megakaryocytes. Decreased platelet survival is associated with an extrinsic rather than an intrinsic platelet defect since normal platelets have a shortened survival in hypoxic mice at 0.3 ATM. The decrease in platelet aggregation is likewise due to a plasma inhibitor since plasma from hypoxic mice inhibits aggregation of normal platelets. The changes in platelet kinetics and aggregation of the mouse exposed to 0.3 ATM for two weeks mimic in many ways those seen in patients with chronic hypoxemia and provide a laboratory model to study these alterations.

Decreased Platelet Survival And Aggregation In Mice Exposed To Hypobaric Hypoxia