Coagulopathy in patients with hemorrhagic fever with renal syndrome

Abstract

Hemorrhagic fever with renal syndrome in Korea (Korean hemorrhagic fever) is an acute viral disease characterized by fever, hemorrhage and renal failure. In Korean patients, the disease manifests more distinctive bleeding tendencies than those of hemorrhagic fever with renal syndrome found in western countries. To investigate the nature and role of the coagulation, fibrinolysis, kinin and immune system in the pathogenesis of such a hemorrhagic manifestation, alterations of these systems were assessed from the early phase of the disease. Decreased platelet count and shortened platelet survival were observed with giant platelets in the peripheral blood. The marked prolongations of bleeding time, prothrombin time and partial thromboplastin time were noticed with the decreased plasma activities of coagulation factors II, V, VIII, IX and X. Shortened half life of fibrinogen, increased fibrinogen-fibrin degradation product, with decreased plasma levels and activities of plasminogen, alpha 2-plasmin inhibitor and antithrombin III were found. On thrombelastogram, the existence of procoagulant activity was confirmed, and prolonged reaction time and clot formation time with decreased maximum amplitude were observed. The appearance of circulating immune complexes was found along with decreased C3 and normal C4 in the serum. Significant decrease of serum C3 was evident in the patients with disseminated intravascular coagulation. These findings of coagulopathy were normalized within ten days of the illness in most cases. Therefore, it can be concluded that disseminated intravascular coagulation and thrombocytopenia in the early phase, and azotemia developing later might play an important role in the pathogenesis of bleeding tendency in Korean hemorrhagic fever.

Haemostatic abnormalities in African swine fever/A comparison of two virus strains of different virulence (Dominican Republic '78 and Malta '78)

“…Because of the tropism of ASF virus for mononuclear cells [5, 16, 18-] and little evidence of its replication in endothelial cells [26,31], one could expect that the effect of ASF virus on these cells would be to induce the release of plasminogen activators, but this remains to be confirmed. In viral haemorrhagic fevers (VHF) of humans, the occurrence, magnitude and relative importance of DIC as a cause of haemorrhage are all related to the severity of illness [6,13,14]. This is in agreement with our results, where the haemostatic abnormalities in pigs infected with Malta '78 (the less virulent ASF virus strain) were less severe than those observed in pigs infected with DR '78.…”

“…Patients with haemorrhagic fever with renal syndrome (HFRS) also developed thrombocytopenia, decrease in the activity of coagulation factors, decreased levels offibrinogen and reduced concentrations of plasminogen and antithrombin III (AT-III) [14].…”

Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model

“…However, the mechanisms of thrombocytopenia in VHFs, and especially in bunyavirus infection, have been elusive. Possible mechanisms for bunyavirus-induced thrombocytopenia have been suggested to include increased platelet consumption in damaged tissues (13,21,22), decreased survival time of platelets (23,24), or infection of megakaryocytes, resulting in decreased platelet production (23,25). Intriguingly, we found in this study that SFTSV colocalized with phagocytosed platelets in cytoplasm of splenic macrophages.…”

Hantaviruses: Molecular Biology, Evolution and Pathogenesis

“…Decreased serum concentration of the complement component C3 during early stages of HFRS correlates with prolonged hemorrhagic manifestations and DIC [121][122][123]. No differences in serum concentration of C4 are found during all stages of HFRS.…”