Fibrin formation and lysis studies in dengue virus infection

Dengue virus is a mosquito-borne human viral pathogen that has recently become a major public health concern particularly in tropical and subtropical countries, predominantly in urban and periurban areas. Plasma from five patients infected by the virus was selected since they have in different degrees prolonged thrombin times: +2.1, +3.4, +5.7, +7.1 and +18.5 s, like a transitory acquired dysfibrinogenemia. The serotype could be determined in only two patients, being DEN-1 and DEN-3. The fibrinogen concentration was normal ranging from 2.5 to 3.2 g/l. In general, the fibrin degradation products of the patients were high, reaching values of 6000 ng/ml. The polymerization process was quite similar to that of the control, except in two cases where the final turbidity was almost half the control value. In one of these patients, the fibrinogen was purified and mixed with normal fibrinogen (v: v); the patients' fibrinogen impaired normal fibrin polymerization. Studies of the fibrinolytic process revealed that clots from dengue patients started to lyze before they have reached the maximum turbidity, although this was not reflected in the time needed for complete clot dissolution, which was similar to that of the control for all the patients. Fibrinolysis of clots made by mixing normal and patient purified fibrinogen (2.5: 1) was impaired. Clot images obtained by scanning electron microscopy showed that the patients' fibrin network had some degree of degradation and the fibers were thicker than those of the control (P < 0.05). This preliminary study seems to indicate that the dengue virus infection modifies the balance of coagulation-fibrinolysis toward hyperfibrinolysis and could modify the normal fibrinogen molecule.