Influence of the genetic background on platelet function, microparticle and thrombin generation in the common...

Genetic background has been shown to affect phenotype in transgenic mice with hemostatic defects. We present comparative data on various platelet function tests, as well as on microparticle and thrombin generation capacity in three mouse strains most commonly used in transgenic applications. Normal, inbred 129Sv (n = 24), C57BL/6 (n = 14) and BALB/c (n = 22) mice were used. BALB/c mice showed statistically significantly longer tail-bleeding times (158 +/- 42 s, P<0.02) than 129Sv (113 +/- 37) and C57BL/6 (122 +/- 29) and paradoxically increased velocity of platelet aggregation (P<0.01) with ADP, collagen, ionophore and thrombin. ATP-release did not differ between strains, it was weakest with ADP and strongest with thrombin. 129Sv platelets were less responsive to thrombin. Generation of platelet microparticles did not differ between strains either and could efficiently be inhibited by EDTA but not by aspirin or alprostadil. Two anti-GPIIIa monoclonal antibodies did not inhibit microparticles either, although they could block aggregation. Thrombin generation was equivalent in C57BL/6 and BALB/c, but slower in 129Sv. Interestingly, the reaction in all strains was immediate and different from the human model in that no lag-phase was seen after triggering. In summary these mouse strains show similar patterns of ex vivo platelet aggregation, bleeding times as well as microparticle and thrombin generation. Subtle differences were found, which should be taken into consideration when interpreting data from wild-type or transgenic models.