Role of platelets, neutrophils, and factor XII in spontaneous venous thrombosis in mice (original) (raw)

Recently, platelets, neutrophils, and factor XII have been implicated as important players in the pathophysiology of venous thrombosis. Their role became evident in mouse models where surgical handlings were used to provoke thrombosis. Inhibition of anticoagulation in mice using small interfering (si) RNA targeting Serpinc1 and Proc also results in a thrombotic phenotype, which is spontaneous (no additional triggers), and reproducibly results in clots in the large veins of the head and fibrin deposition in the liver. This thrombotic phenotype is fatal, but can be fully rescued by thrombin inhibition. In the present study, this model was used to investigate the role of platelets, neutrophils, and factor XII. After administration of siRNAs targeting Serpinc1 and Proc, antibody-mediated depletion of platelets fully abrogated the clinical features as well as microscopic aspects in the head. This was corroborated by strongly reduced fibrin deposition in the liver. Whereas neutrophils wer...