GPVI and CLEC-2 contribution to the prevention of inflammatory bleeding by platelets. (A) Transgenic hIL-4Rα/GPIbα mice were immunodepleted for platelets and transfused or not with control wild-type platelets, or with platelets with a deficiency in GPVI (JAQ1 WT platelets), CLEC-2 (Clec2^−/− platelets), GPVI and CLEC-2 (JAQ1 Clec2^−/− platelets), or in SLP76 (Slp76^−/− platelets). Mice were then challenged with the cutaneous reverse passive Arthus reaction rpA and compared for inflammatory bleeding at the reaction site. Representative images of challenged skin (reaction spots are outlined) are shown above the bar graphs, which represent the mean hemoglobin content at the reaction site. Unlike control wild-type platelets, platelets with a deficiency in GPVI or CLEC-2 only partially prevented inflammatory bleeding. Notably, platelets with a combined deficiency in GPVI and CLEC-2, or platelets lacking Slp76, a signaling adapter protein downstream of GPVI and CLEC-2, did not prevent bleeding when transfused to thrombocytopenic hIL-4Rα/GPIbα–mice. Adapted from Boulaftali et al³²  with permission. (B) Representative photographs showing that GPVI^−/− mice with normal platelet count (GPVI^−/− 100% platelets) are sensitized to rpa-induced skin bleeding. Adapted from Gros et al.³⁴