Rotational thromboelastometry alongside conventional coagulation testing in patients with Crimean–Congo haemorrhagic fever: an observational cohort study

Abstract

Background Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease. MethodsWe did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean-Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38-79 s), clot formation time (34-159 s), amplitude at 10 min after clotting time (43-65 mm), maximum clot firmness (50-72 mm), and maximum lysis (>15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7-23 mm) and maximum clot firmness (9-25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS. Findings Between May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean-Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11•1-31•8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42-81; IQR 48-64) versus 69 s (range 48-164; IQR 54-75; p=0•01); mean amplitude at 10 min after clotting time 45•1 mm (SD 7•0) versus 33•9 mm (SD 8•6; p<0•0001); median clot formation time 147 s (range 72-255; IQR 101-171) versus 197 s (range 98-418; IQR 156-296; p=0•006); and maximum clot firmness 54•4 mm (SD 7•2) versus 45•1 mm (SD 12•5; p=0•003). The EXTEM S variables were compared at different time points; maximum clot firmness (p=0•024) and amplitude at 10 min after clotting time (p=0•090) were lowest on days 4-6 of illness. We found no significant differences in FIBTEM variables between mild and moderate to severe cases (median amplitude at 10 min, 13 mm [range 8-20; IQR 11-15] vs 12 mm [range 6-25; IQR 10-15; p=0•68]; and median maximum clot firmness, 15 mm [range 9-60; IQR 13-21] vs 17 mm [range 7-39; IQR 13-23; p=0•21]); and no hyperfibrinolysis (maximum lysis >15%).Interpretation Coagulopathy of Crimean-Congo haemorrhagic fever is related to defects in clot development and stabilis...

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis

“…In addition to conventional laboratory parameters, rotational thromboelastometry (ROTEM) provides evidence for net coagulation capacity and insight into clot formation time, clot firmness and fibrinolysis in the critically ill patients [ 12 ]. Here we report ROTEM data in 40 consecutive, severely ill COVID-19 patients treated in two tertiary intensive care units (ICUs) and assessed the association with thromboembolic complications.…”

Rotational thromboelastometry in critical phase of dengue infection: Association with bleeding

“… 18 , 19 The findings of the study on Crimean‐ Congo hemorrhagic fever found that mucosal bleeding was not due to thrombocytopenia but rather due to platelet dysfunction in aggregation. 18 …”

“…Further clinical correlation demonstrated that lower AUC may indicate the severity of the disease and may correlate with the duration of the hospital stay 17 . In the context of other viral hemorrhagic fevers such as Crimean‐Congo hemorrhagic fever, Lassa fever, and Argentinian hemorrhagic fever, platelet aggregometry studies have suggested that the coagulopathy is clearly due to defects in platelet function and aggregation 18,19 . The findings of the study on Crimean‐ Congo hemorrhagic fever found that mucosal bleeding was not due to thrombocytopenia but rather due to platelet dysfunction in aggregation 18 …”

“…17 In the context of other viral hemorrhagic fevers such as Crimean-Congo hemorrhagic fever, Lassa fever, and Argentinian hemorrhagic fever, platelet aggregometry studies have suggested that the coagulopathy is clearly due to defects in platelet function and aggregation. 18,19 The findings of the study on Crimean-Congo hemorrhagic fever found that mucosal bleeding was not due to thrombocytopenia but rather due to platelet dysfunction in aggregation. The observation that bleeding occurs in patients with dengue fever with normal platelet counts also provides evidence that alteration in platelet function, activation, and aggregation is probably the key factor in the pathogenesis of bleeding in dengue.…”

Serum thrombin‐activatable fibrinolysis inhibitor levels and its relation with pathogenesis and bleeding and prognosis in patients with Crimean Congo hemorrhagic fever

“…When TAFI comes into contact with the thrombin‐thrombomodulin complex, it is converted into TAFI‐a (the active form). TAFI‐a is involved in coagulation, fibrinolysis, and inflammation 15 . It remains to be elucidated whether TAFI levels or TAFI activity better reflects the effect on coagulation system.…”