Mechanisms of HFV-induced thrombocytopenia Direct Platelet Destructiona Immune destruction of plateletb Megakaryocyte impairmentc Inhibition of platelet functiond Hantavirus [166] SFTS [69] Hantavirus [139] Hantavirus [166]   DENV [112,167,168] DENV [169] LASV [71]     JUNV [74,170] JUNV [72]       Ebola [62] aDestruction of platelets by direct interaction: SomeHFV can bind platelets directly causing activation and granules release. bImmunological destruction of platelet-virus complexes: Thrombocytopenia can be mediated by macrophages sequestration of platelet-virus complexes at the local site or/and in the spleen, platelets-virus-leukocyte aggregation and subsequent phagocytosis by macrophages or destruction mediated by platelet-virus associated antibodies. cMegakaryocytes or Megakaryocyte precursors impairment: Some HFV can infect megakaryocytes or their precursor causing reduction in platelets number or impairment in their function. dInhibition of platelet function: Some unidentified soluble factors present in plasma from infected patients can inhibit aggregation of platelets from healthy individuals.

Table 1: Four main mechanisms by which Haemorrhagic fever viruses (HFV) can induce thrombocytopenia.