CASP8 and Lymphadenopathy: As expected, MlklPf4Δ/Pf4Δ and Caspase-8Pf4Δ/Pf4ΔMlklPf4Δ/Pf4Δ megakaryocytes were resistant to TSI-induced necroptosis (Supplementary Fig. 6), demonstrating efficient conditional deletion of Mlkl. Although Caspase-8−/−Mlkl−/− mice rapidly develop severe lymphadenopathy, systemic autoimmune disease, and thrombocytopenia41, Caspase-8Pf4Δ/Pf4ΔMlklPf4Δ/Pf4Δ DKO mice were viable and fertile and did not exhibit any changes in platelet counts or other peripheral blood counts compared to wild-type floxed littermate controls (Table 1).