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

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. METHODS: We 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 stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean-Congo haemorrhagic fever relates to platelet dysfunction. FUNDING: Wellcome Trust, UK Ministry of Defence, and National Institute for Health Research Health Protection Research Unit.

Significance of IL-1Ra and IL-6 gene variants in Turkish patients with Crimean-Congo hemorrhagic fever

Objective: To investigate the association between IL-1Ra variable number of tandem repeat (rs2234663), IL-6 -597GA (rs1800797), IL-6 -572GC (rs1800796) and the risk of Crimean-Congo hemorrhagic fever (CCHF) in the Turkish patients. Methods: This study included 50 patients infected with CCHF and 50 healthy controls. These variants were genotyped using polymerase chain reaction and/or restriction fragment length polymorphism method. Results:The distribution of the IL-6 -572GC genotypes and alleles varied significantly between the patients and the controls. The subjects carrying IL-6 -572GC GG genotype and G allele had increased risk of developing CCHF compared to the control group (P=0.006, P=0.014, respectively). IL-6 -572GC GC genotype was higher in the controls than the patients (P=0.006). For the triple genotype combinations, the 1/2-GC-GG genotype combination was detected more frequently in the control group than CCHF patients (P=0.016). IL-6 (-572/-597) GG-GG genotype was significantly higher in the patient group (P=0.015), while the GC-GG genotype was significantly lower in the patient group (P=0.005). Additionally, the G-G haplotype was significantly higher in the patient group (P=0.042), whereas C-G was found to be significantly lower in the patients than the control group (P=0.037). Conclusions: The results of this study suggest the IL-6 -572GC variant might be genetic markers of sensitivity to CCHF in the Turkish population and may facilitate greater protection against the disease.

Predictors of histological indication for treatment in HBeAg negative chronic HBV infection.

In this study, we evaluated the relationship of hepatitis B virus (HBV) DNA levels with liver histology and various other liver related parameters and the predictors of histologically active liver disease requiring treatment (Histological activity ≥6 and/or grade ≥2 by Ishak's classification) in patients with HBeAg negative chronic HBV infection. Demographic data, laboratory findings and liver histology findings of patients with no clinical cirrhosis who underwent liver biopsy considering HBeAg negative chronic hepatitis (HBV DNA >2000 IU/mL) were analyzed. Two hundred and fifteen patients were included in this retrospective study. Treatment indication by histologic findings were 85.7%, 61.2%, and 64%, respectively, in group 1 (HBV DNA ≥200 000), group 2 (HBV DNA 20 000-200 000), and group 3 (HBV DNA 2000-20 000 IU/mL) (P = 0.001). Group 1 was different from other groups in terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fibrosis stage, necroinflammatory activity, and platelet count. Multiple logistic regression analysis revealed that, advanced age (cut-off was 46 years), higher than normal AST and HBV DNA ≥200 000 IU/mL (compared to group 3) were found to be the predictors of histologically active disease with treatment indication. Conclusively, most of the patients with HBV DNA ≥200 000 IU/mL showed treatment requiring liver injury, but also a significant portion of the patients with HBV DNA 2000-200 000 IU/mL carried an indication for treatment. Although age (>46 years) and AST (>40 IU/L) can be helpful to predict treatment requirement in patients with HBV DNA 2000-200 000 IU/mL, sufficient effort should be made to find out the significant liver damage.