Table 1.
Common characteristics of hemorrhagic fever viruses.
Figure 1.
Geographical distribution of Viral Hemorrhagic Fevers (VHF).
This map shows the global distribution of some members of the viral families related to hemorrhagic fever disease. CCHF stands for Crimean Congo Hemorrhagic Fever and SFTS for severe fever with thrombocytopenia syndrome.
Table 2.
Impact of hemorrhagic fever viruses.
Table 3.
Hemorrhagic fever virus findings related to coagulation disorders.
Figure 2.
Platelets have multiple surface receptors, a cannalicular system, microtubules, mitochondria, three types of granules (lysosomal, alpha, and dense), and deposits of small factors like glycogen (Figure 2 and 3) [54]. Whereas dense granules contain factors that potentiate platelet activation, α-granules contain growth factors and clotting proteins that contribute to hemostasis [130].
Figure 3.
Membrane glycoproteins of platelets include GPIa, GPIIb/IIIa (aIIbb3), or VLA-5 (fibrinogen receptor); GPIb/IX/V (vW and Mac-1 receptor); GPIc'-IIa or VLA-6 (laminin receptor); and a2b1 GPVI (Collagen receptor). Alpha granules contain P-selectin; platelet factor 4; transforming factor-b1; chemokines; proteoglycan; platelet-derived growth factor; a2-plasmin inhibitor; vitronectin; laminin; CD63; TGFbeta; CLEC-2; thrombospondin; fibronectin; B-thromboglobulin; vWF; fibrinogen; coagulation factors V, XI, and XIII; integrins; thrombocidins; proteases; thrombin; prothrombin; kininogens; immunoglobulin family receptors; leucine-rich repeat family receptors; and other proinflammatory and immune-modulating factors. Dense granules hold ADP, ATP, calcium, serotonin, histamine, dopamine, phosphate, eicosanoids. Receptors for primary agonist include P2X, P2Y1, and P2Y12 (ADP); TPa-R and TPb-R (TXA2); PAR-1 and PAR-4 (thrombin); PAFR (platelet-activating factor); 5-HT2A (Serotonine); epinephrine receptors (catecholamines); Fc and complement C3a/C5a receptors; and TLRs, CD40, CD40L, ICAM-2, DC-SIGN, JAM-A, and FcγRII. Between the platelet Metabolites are TXA2, sphingosine-1-phopate, PAF, glycogen, platelet factor 4 (PF-4), RANTES, connective tissue activating peptide 3 (CTAP-3), platelet basic protein, thymosin β-4 (Tβ-4), fibrinopeptide B (FP-B), and fibrinopeptide A (FP-A).
Table 4.
Four main mechanisms by which HFVs induce thrombocytopenia.
Figure 4.
Immunological destruction of platelets.
Platelets can interact with macrophages and neutrophils at the infection site and/or in the spleen through immuno-complexes or directly by cellular-ligand interactions. These interactions lead to either platelet sequestration or platelet destruction mediated by the immune system.