Object: Although thrombin burst has attracted attention as a physiological coagulation mechanism, clinical evidence from a routine assay for it is scarce. This mechanism was therefore evaluated by a clot waveform analysis (CWA) to assess the thrombin time (TT). Material and Methods: The TT with a low concentration of thrombin was evaluated using a CWA. We evaluated the CWA-TT of plasma deficient in various clotting factors, calibration plasma, platelet-poor plasma (PPP), and platelet-rich plasma (PRP) obtained from healthy volunteers, patients with thrombocytopenia, and patients with malignant disease. Results: Although the TT-CWA of calibration plasma was able to be evaluated with 0.01 IU/mL of thrombin, that of FVIII-deficient plasma could not be evaluated. The peak time of CWA-TT was significantly longer, and the peak height significantly lower, in various deficient plasma, especially in FVIII-deficient plasma compared to calibration plasma. The second peak of the first derivative (1st DP-2) was detected in PPP from healthy volunteers, and was shorter and higher in PRP than in PPP. The 1st DP-2 was not detected in PPP from patients with thrombocytopenia, and the 1st DP-2 in PRP was significantly lower in patients with thrombocytopenia and significantly higher in patients with malignant disease than in healthy volunteers. Conclusion: The CWA-TT became abnormal in plasma deficient in various clotting factors, and was significantly affected by platelets, suggesting that the CWA-TT may be a useful test for hemostatic abnormalities.

Background: Acute cerebral infarction (ACI) includes cardiogenic ACI treated with anticoagulants and atherosclerotic ACI treated with antiplatelet agents. The differential diagnosis between cardiogenic and atherosclerotic ACI is still difficult. Materials and Methods: The plasma sCLEC-2 and D-dimer levels were measured using the STACIA system. Results: The plasma sCLEC-2 level was significantly high in patients with ACI, especially those in patients with atherosclerotic or lacunar ACI, and plasma D-dimer levels were significantly high in patients with cardioembolic ACI. The plasma levels of sCLEC-2 and the sCLEC-2/D-dimer ratios in patients with atherosclerotic or lacunar ACI were significantly higher than those in patients with cardioembolic ACI. The plasma D-dimer levels in patients with atherosclerotic or lacunar ACI were significantly lower than those in patients with cardioembolic ACI. The plasma levels of sCLEC-2 and the sCLEC-2/D-dimer ratios were significantly higher in patients with atherosclerotic or lacunar ACI or acute myocardial infarction in comparison to patients with cardioembolic ACI or those with deep vein thrombosis. Conclusion: Using both the plasma sCLEC-2 and D-dimer levels may be useful for the diagnosis of ACI, and differentiating between atherosclerotic and cardioembolic ACI.

Although thrombosis in coronavirus disease 2019 (COVID-19) infection has attracted attention, the mechanism underlying its development remains unclear. The relationship between platelet activation and the severity of COVID-19 infection was compared with that involving other infections. Plasma soluble C-type lectin-like receptor 2 (sCLEC-2) levels were measured in 46 patients with COVID-19 infection and in 127 patients with other infections. The plasma sCLEC-2 levels in patients with COVID-19 infection {median (25th, 75th percentile), 489 (355, 668) ng/L} were significantly higher (p < 0.001) in comparison to patients suffering from other pneumonia {276 (183, 459) ng/L}, and the plasma sCLEC-2 levels of COVID-19 patients with severe {641 (406, 781) ng/L} or critical illness {776 (627, 860) ng/L} were significantly higher (p < 0.01, respectively) in comparison to those with mild illness {375 (278, 484) ng/L}. The ratio of the sCLEC-2 levels to platelets in COVID-19 patients with critical illness of infection was significantly higher (p < 0.01, p < 0.001 and p < 0.05, respectively) in comparison to COVID-19 patients with mild, moderate or severe illness. Plasma sCLEC-2 levels were significantly higher in patients with COVID-19 infection than in those with other infections, suggesting that platelet activation is triggered and facilitated by COVID-19 infection.

The scoring systems for disseminated intravascular coagulation (DIC) criteria require several adequate cutoff values, vary, and are complicated. Accordingly, a simpler and quicker diagnostic method for DIC is needed. Under such circumstances, soluble C-type lectin-like receptor 2 (sCLEC-2) received attention as a biomarker for platelet activation. Materials and Methods: The diagnostic usefulness of sCLEC-2 and several formulas, including sCLEC-2xD-dimer, sCLEC-2/platelet count (sCLEC-2/PLT), and sCLEC-2/PLT × D-dimer (sCLEC-2xD-dimer/PLT), were evaluated among 38 patients with DIC, 39 patients with pre-DIC and 222 patients without DIC or pre-DIC (non-DIC). Results: Although the plasma level of sCLEC-2 alone was not a strong biomarker for the diagnosis of DIC or pre-DIC, the sCLEC-2xD-dimer/PLT values in patients with DIC were significantly higher than those in patients without DIC, and in a receiver operating characteristic (ROC) analysis for the diagnosis of DIC, sCLEC-2xD-dimer/PLT showed the highest AUC, sensitivity, and odds ratio. This formula is useful for the diagnosis of both pre-DIC and DIC. sCLEC-2xD-dimer/PLT values were significantly higher in non-survivors than in survivors. Conclusion: The sCLEC-2xD-dimer/PLT formula is simple, easy, and highly useful for the diagnosis of DIC and pre-DIC without the use of a scoring system.

Object: Although many Japanese patients infected with coronavirus disease 2019 (COVID-19) only experience mild symptoms, in some cases a patient’s condition deteriorates, resulting in a poor outcome. This study examines the behavior of biomarkers in patients with mild to severe COVID-19. Methods: The disease severity of 152 COVID-19 patients was classified into mild, moderate I, moderate II, and severe, and the behavior of laboratory biomarkers was examined across these four disease stages. Results: The median age and male/female ratio increased with severity. The mortality rate was 12.5% in both moderate II and severe stages. Underlying diseases, which were not observed in 45% of mild stage patients, increased with severity. An ROC analysis showed that C-reactive protein (CRP), ferritin, procalcitonin (PCT), hemoglobin (Hb) A1c, albumin, and lactate dehydrogenase (LDH) levels were significantly useful for the differential diagnosis of mild/moderate I stage and moderate II/severe stage. In the severe stage, Hb levels, coagulation time, total protein, and albumin were significantly different on the day of worsening from those observed on the day of admission. The frequency of hemostatic biomarker abnormalities was high in the severe disease stage. Conclusion: The evaluation of severity is valuable, as the mortality rate was high in the moderate II and severe stages. The levels of CRP, ferritin, PCT, albumin, and LDH were useful markers of severity, and hemostatic abnormalities were frequently observed in patients in the severe disease stage.