Detection of a Prethrombotic State in Patients with Hepatocellular Carcinoma, Using a Clot Waveform Analysis.

Background: Although hepatocellular carcinoma (HCC) is frequently associated with thrombosis, it is also associated with liver cirrhosis (LC) which causes hemostatic abnormalities. Therefore, hemostatic abnormalities in patients with HCC were examined using a clot waveform analysis (CWA). Methods: Hemostatic abnormalities in 88 samples from HCC patients, 48 samples from LC patients and 153 samples from patients with chronic liver diseases (CH) were examined using a CWA-activated partial thromboplastin time (APTT) and small amount of tissue factor induced FIX activation (sTF/FIXa) assay. Results: There were no significant differences in the peak time on CWA-APTT among HCC, LC, and CH, and the peak heights of CWA-APTT were significantly higher in HCC and CH than in HVs and LC. The peak heights of the CWA-sTF/FIXa were significantly higher in HCC than in LC. The peak times of the CWA-APTT were significantly longer in stages B, C, and D than in stage A or cases of response. In the receiver operating characteristic (ROC) curve, the fibrin formation height (FFH) of the CWA-APTT and CWA-sTF/FIXa showed the highest diagnostic ability for HCC and LC, respectively. Thrombosis was observed in 13 HCC patients, and arterial thrombosis and portal vein thrombosis were frequently associated with HCC without LC and HCC with LC, respectively. In ROC, the peak time×peak height of the first derivative on the CWA-sTF/FIXa showed the highest diagnostic ability for thrombosis. Conclusion: The CWA-APTT and CWA-sTF/FIXa can increase the evaluability of HCC including the association with LC and thrombotic complications.

Super Formula for Soluble C-Type Lectin-Like Receptor 2 × D-Dimer in Patients With Acute Cerebral Infarction.

Acute cerebral infarction (ACI) includes atherosclerotic and cardiogenic ACI and involves a thrombotic state, requiring antithrombotic treatment. However, the thrombotic state in ACI cannot be evaluated using routine hemostatic examinations. Plasma soluble C-type lectin-like receptor 2 (sCLEC-2) and D-dimer levels were measured in patients with ACI. Plasma sCLEC-2 and D-dimer levels were significantly higher in patients with ACI than in those without it. The sCLEC-2 × D-dimer formula was significantly higher in patients with ACI than in those without it. A receiver operating characteristic curve showed a high sensitivity, area under the curve, and odds for diagnosing ACI in the sCLEC-2 × D-dimer formula. Although the sCLEC-2 and D-dimer levels were useful for the differential diagnosis between cardiogenic and atherosclerotic ACI, the sCLEC-2 × D-dimer formula was not useful. sCLEC2 and D-dimer levels are useful for the diagnosis of ACI and the sCLEC2 × D-dimer formula can enhance the diagnostic ability of ACI, and sCLEC2 and D-dimer levels may be useful for differentiating between atherosclerotic and cardioembolic ACI.

The Evaluation of Clot Waveform Analyses for Assessing Hypercoagulability in Patients Treated with Factor VIII Concentrate.

BACKGROUND: Regular prophylactic therapy has become an increasingly common treatment for severe hemophilia. Therefore, hypercoagulability-a potential risk factor of thrombosis-is a cause for concern in hemophilic patients treated with a high dose of FVIII concentrate. In clot waveform analysis (CWA)-thrombin time (TT), a small amount of thrombin activates clotting factor VIII (FVIII) instead of fibrinogen, resulting in FVIII measurements using CWA-TT with a small amount of thrombin. METHODS: The coagulation ability of patients treated with FVIII concentrate or emicizumab was evaluated using activated partial thromboplastin time (APTT), TT and a small amount of tissue factor-induced FIX activation assay (sTF/FIXa) using CWA. RESULTS: The FVIII activity based on CWA-TT was significantly greater than that based on the CWA-APTT or chromogenic assay. FVIII or FVIII-like activities based on the three assays in plasma without emicizumab were closely correlated; those in plasma with emicizumab based on CWA-TT and chromogenic assays were also closely correlated. CWA-APTT and CWA-TT showed different patterns in patients treated with FVIII concentrates compared to those treated with emicizumab. In particular, CWA-TT in patients treated with FVIII concentrate showed markedly higher peaks in platelet-rich plasma than in platelet-poor plasma. CWA-APTT showed lower coagulability in hemophilic patients treated with FVIII concentrate than in healthy volunteers, whereas CWA-sTF/FIXa did not. In contrast, CWA-TT showed hypercoagulability in hemophilic patients treated with FVIII concentrate. CONCLUSIONS: CWA-TT can be used to evaluate the thrombin bursts that cause hypercoagulability in patients treated with emicizumab. Although routine APTT evaluations demonstrated low coagulation ability in patients treated with FVIII concentrate, CWA-TT showed hypercoagulability in these patients, suggesting that the evaluation of coagulation ability may be useful when using multiple assays.

Super Formula for Diagnosing Disseminated Intravascular Coagulation Using Soluble C-Type Lectin-like Receptor 2.

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.

Clot Waveform Analysis for Hemostatic Abnormalities.

Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.

Thrombotic Mechanism Involving Platelet Activation, Hypercoagulability and Hypofibrinolysis in Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) has spread, with thrombotic complications being increasingly frequently reported. Although thrombosis is frequently complicated in septic patients, there are some differences in the thrombosis noted with COVID-19 and that noted with bacterial infections. The incidence (6-26%) of thrombosis varied among reports in patients with COVID-19; the incidences of venous thromboembolism and acute arterial thrombosis were 4.8-21.0% and 0.7-3.7%, respectively. Although disseminated intravascular coagulation (DIC) is frequently associated with bacterial infections, a few cases of DIC have been reported in association with COVID-19. Fibrin-related markers, such as D-dimer levels, are extremely high in bacterial infections, whereas soluble C-type lectin-like receptor 2 (sCLEC-2) levels are high in COVID-19, suggesting that hypercoagulable and hyperfibrinolytic states are predominant in bacterial infections, whereas hypercoagulable and hypofibrinolytic states with platelet activation are predominant in COVID-19. Marked platelet activation, hypercoagulability and hypofibrinolytic states may cause thrombosis in patients with COVID-19.

Plasma Soluble Fibrin Is Useful for the Diagnosis of Thrombotic Diseases.

BACKGROUND: Soluble fibrin (SF) is a form of fibrinogen that is activated by thrombin and is considered to be useful for the diagnosis of the prethrombotic state or thrombosis. METHODS: Plasma levels of fibrin-related markers (FRMs), such as SF, D-dimer, fibrinogen, and fibrin degradation prioduct (FDP) levels in critically ill patients, were examined for the diagnosis of disseminated intravascular coagulation (DIC), venous thromboembolism (VTE), peripheral arterial thromboembolism (PATE), acute myocardial infarction (AMI), and acute cerebral infarction (ACI). RESULTS: FRMs showed the usefulness in diagnosing DIC and VTE and the cutoff values of D-dimer, FDP, and SF for DIC were 7.2-7.8 µg/mL, 10.0 µg/mL, and 9.5 µg/mL, respectively. The cutoff values of D-dimer and FDP for VTE were similar to the 97.5th percentile values of healthy volunteers, while the cutoff value of SF was 6.9 µg/mL. In AMI and ACI, the cutoff values of D-dimer and FDP were lower than the 97.5 percentile values of healthy volunteers. A receiver operating characteristic analysis for all thrombosis cases showed that an adequate cutoff value in only SF among FRMs was higher than the confidence interval of healthy volunteers. Only SF had high sensitivity for thrombosis, as the FDP/SF ratio was markedly low for ACI, AMI and VTE. CONCLUSIONS: FRMs, especially D-dimer and FDP, were useful for diagnosing thrombosis with hyperfibrinolysis (e.g., DIC). As SF showed high sensitivity for predominantly thrombotic diseases, including arterial thrombosis, such as ACI and AMI, a high SF value suggests the possibility of an association with thrombosis. Finally, SF is the most useful marker for raising suspicion of an association with thrombosis, especially arterial thrombosis.

The Detection of Hypercoagulability in Patients with Acute Cerebral Infarction Using a Clot Waveform Analysis.

A few studies concerning hypercoagulable states have sufficiently been reported in patients with acute cerebral infarction (ACI), as ACI is generally considered to be caused by platelet activation. Clot waveform analyses (CWA) for activated partial thromboplastin time (APTT) and small amount of tissue factor FIX activation assay (sTF/FIXa) were examined in 108 patients with ACI, 61 patients without ACI, and 20 healthy volunteers. CWA-APTT and CWA-sTF/FIXa showed that the peak heights were significantly higher in ACI patients without anticoagulant therapy than in healthy volunteers. Absorbance exceeding 78.1 mm on the 1st DPH in the CWA-sTF/FIXa showed the highest odds ratio for ACI. The peak heights were significantly lower in the CWA-sTF/FIXa of ACI patients receiving argatroban therapy than in those of ACI patients without anticoagulant therapy. CWA can suggest a hypercoagulable state in ACI patients and may be useful for monitoring the need for anticoagulant therapy.

Reply to Ishikura, H. What Does Soluble C-Type Lectin-like Receptor 2 (sCLEC-2) × D-Dimer/Platelet (PLT) (sCLEC-2 × D-Dimer/PLT) Mean for Coagulation/Fibrinolysis Conditions? Comment on "Yamamoto et al. Super Formula for Diagnosing Disseminated Intravascular Coagulation Using Soluble C-Type Lectin-like Receptor 2. Diagnostics 2023, 13, 2299".

We would like to thank Dr. Ishikura for his kind comment [...].

A Clot Waveform Analysis of Thrombin Time Using a Small Amount of Thrombin Is Useful for Evaluating the Clotting Activity of Plasma Independent of the Presence of Emicizumab.

OBJECTIVE: Although emicizumab is a bispecific, monoclonal antibody that has led to a significant improvement of treatment for hemophilia A patients with inhibitors, the routine monitoring of patients treated with emicizumab is difficult. Thrombin time (TT) reflects thrombin burst, which mainly depends on activation of factor V (FV) and FVIII. METHODS: We, therefore, developed a method for evaluating clotting activity independent of the presence of emicizumab. Normal plasma (NP) or FVIII-deficient plasma (FVIIIDP) with and without emicizumab was measured using clot waveform analysis (CWA)-activated partial thromboplastin time (APTT) and TT. RESULTS: Emicizumab caused clot formation in FVIIIDP using the CWA-APTT; however, the coagulation peaks of plasma with and without emicizumab measured by the CWA-TT did not differ to a statistically significant extent. Regarding the mixing tests with NP and FVIIIDP, CWA-APTT showed large differences between each mixing test in plasma with and without emicizumab, whereas the CWA-TT showed similar patterns in mixing plasma with and without emicizumab. Regarding the standard curve of FVIII activity, the CWA-APTT showed an FVIII-concentration-dependent increase; however, the values with each concentration of FVIII differed between samples with and without emicizumab, whereas CWA-TT showed FVIII-concentration-dependent fluctuations independent of the presence of emicizumab, and the values with each concentration of FVIII were similar in samples with and without emicizumab. CONCLUSIONS: As CWA-TT using a small amount of thrombin (0.5 IU/mL) can reflect thrombin burst and be useful for evaluating FVIII activity, independent of the presence of emicizumab, it is useful for monitoring clotting activity in patients with an anti-FVIII inhibitor treated with emicizumab.

[Intraoperative Aortic Dissection during Mitral Valve Plasty:Report of a Case].

We report the case of a 74-year-old woman who underwent mitral valve plasty for mitral regurgitation. During the surgery, the ascending aorta was dilated and turned dark red after aortic cannulation. Intraoperative transesophageal echocardiography and direct epiaortic echography revealed type A aortic dissection. In addition to mitral valve plasty, replacement of the ascending aorta was performed under hypothermic circulatory arrest. The postoperative course was uneventful. Because intraoperative aortic dissection is a rare complication, its rapid identification and appropriate management is essential.

Elevated Plasma Soluble C-Type Lectin-like Receptor 2 Is Associated with the Worsening of Coronavirus Disease 2019.

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.

Proposal of Quick Diagnostic Criteria for Disseminated Intravascular Coagulation.

BACKGROUND: The diagnostic criteria for disseminated intravascular coagulation (DIC) vary and are complicated and the cut-off values are different. Simple and quick diagnostic criteria for DIC are required in physicians for critical care. MATERIAL AND METHODS: Platelet counts, prothrombin time-international normalized ratio (PT-INR) and D-dimer levels were examined in 1293 critical ill patients. Adequate cut-off values of these parameters were determined and a quick DIC score using these biomarkers was proposed. The quick DIC score was evaluated using a receiver operating characteristic (ROC) analysis. RESULTS: Using the Japanese Ministry of Health, Labor and Welfare diagnostic criteria, 70 and 109 patients were diagnosed with DIC and pre-DIC, respectively. The ROC analysis of factors difference between DIC and non-DIC, revealed the following cut-off values: PT-INR, 1.20; platelet count, 12.0 × 1010/L and D-dimer, 10.0 µg/mL. Based on the above results, the quick DIC score system was proposed. All patients with DIC had a quick DIC score of 3, 4 or 5, and 85.3% of the patients with pre-DIC had a quick DIC score of ≥3 points. All patients with pre-DIC had a score of ≥2 points. In the ROC analysis, the area under the curve was 0.997 for DIC vs. non-DIC, and 0.984 for pre-DIC + DIC vs. non-DIC, and the cut-off value was 3 points for DIC and 2 points for DIC + pre-DIC. The quick DIC scores of non-survivors were significantly higher than those of survivors. CONCLUSIONS: The Quick DIC score system is a simple and useful tool that can be used for the diagnosis of DIC and pre-DIC. Further evaluation of the quick DIC score system in a large-scale study is required.

D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases.

INTRODUCTION: Although D-dimer is a useful biomarker of thrombosis, there are many D-dimer kits, with high and low fibrinogen and fibrin degradation products (FDP)/ D-dimer ratios. METHODS: Plasma D-dimer levels were measured using three different kits in critically ill patients to examine the usefulness of such measurements for detecting the thrombotic diseases and determining the correlation with the FDP and FDP/D-dimer ratio. RESULTS: Although three D-dimer kits showed marked utility for diagnosing disseminated intravascular coagulation (DIC) and peripheral arterial and venous thromboembolism (PAVTE), the D-dimer levels determined using the three kits varied among diseases. Indeed, one D-dimer kit showed a high FDP/D-dimer ratio, and another kit showed a low FDP/D-dimer ratio. D-dimer kit with low FDP/D-dimer ratio tended to have high cut-off values and low specificity for diagnosing DIC and PAVTE. In D-dimer kit with high FDP/D-dimer ratio, FDP/D-dimer ratios in patients with thrombosis was significantly higher than that in patients without thrombosis. CONCLUSION: All three D-dimer kits show utility for detecting thrombotic diseases. However, the D-dimer levels determined using the kits varied due to differences in the FDP/D-dimer ratio. In combination with the FDP level, a D-dimer kit with a high FDP/D-dimer ratio may be useful.

Clot Waveform Analysis Demonstrates Low Blood Coagulation Ability in Patients with Idiopathic Thrombocytopenic Purpura.

BACKGROUND: Although platelets, which contain large amounts of phospholipids, play an important role in blood coagulation, there is still no routine assay to examine the effects of platelets in blood coagulation. METHODS: Hemostatic abnormalities in patients with thrombocytopenia, including those with idiopathic thrombocytopenic purpura (ITP), were examined using clot wave analysis (CWA)-small-amount tissue-factor-induced FIX activation (sTF/FIXa) and thrombin time (TT). RESULTS: Although there were no marked differences in the three parameters of activated partial thromboplastin time (APTT) between normal healthy volunteers and typical patients with ITP, the peak heights of the CWA-sTF/FIXa were markedly low in patients with ITP. The three peak times of the CWA-sTF/FIXa in patients with a platelet count of ≤8.0 × 1010/L were significantly longer than those in patients with a platelet count > 8.0 × 1010/L and the peak heights of the CWA-sTF/FIXa in patients with a platelet count of ≤8.0 × 1010/L were significantly lower than those in patients with >8.0 × 1010/L. The peak heights of the CWA-APTT in patients with ITP were significantly lower than in patients with other types of thrombocytopenia. The three peak heights of the CWA-sTF/FIXa in ITP patients were significantly lower than those in patients with other types of thrombocytopenia. The CWA-TT showed lower peak heights and longer peak times in patients with ITP in comparison to patients with other types of thrombocytopenia. CONCLUSIONS: The CWA-sTF/FIXa and CWA-TT results showed that blood coagulation is enhanced by platelets and that the blood coagulation ability in ITP patients was low in comparison to healthy volunteers and patients with other types of thrombocytopenia.

The Reevaluation of Thrombin Time Using a Clot Waveform Analysis.

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.

A Clot Waveform Analysis Showing a Hypercoagulable State in Patients with Malignant Neoplasms.

(1) Objective: hypercoagulability in patients with malignant neoplasm were evaluated to examine the relationship with thrombosis. (2) Methods: clot waveform analysis (CWA)-activated partial thromboplastin time (APTT) and CWA-small amount of tissue factor induced FIX activation (sTF/FIXa) assays were performed in 92 patients with malignant neoplasm and the relationship between hypercoagulability and thrombosis was retrospectively examined. (3) Results: The study population included 92 patients with malignant neoplasms. Twenty-six (28.3%) had thrombotic diseases and 9 (9.8%) patients died within 28 days after the CWA. The peak time of the CWA-APTT could not show hypercoagulability in patients with malignant neoplasms. There were almost no significant differences in the peak times of the sTF/FIXa among patients with malignant neoplasms and healthy volunteers. In contrast, the peak heights of the CWA-sTF/FIXa in patients with various malignant neoplasms were significantly higher than those in healthy volunteers. Furthermore, among patients with malignant neoplasms, the peak heights of the sTF/FIXa in patients with thrombosis were significantly higher than those in patients without thrombosis. (4) Conclusions: although the routine APTT cannot evaluate the hypercoagulability, the peak heights of CWA-sTF/FIXa were significantly high in patients with malignant neoplasms, especially in those with thrombosis, suggesting that an elevated peak height of the CWA-sTF/FIXa may be a risk factor for thrombosis.

Evaluation of Biomarkers of Severity in Patients with COVID-19 Infection.

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.

Soluble C-Type Lectin-Like Receptor 2 Elevation in Patients with Acute Cerebral Infarction.

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.

Soluble C-Type Lectin-Like Receptor 2 Is a Biomarker for Disseminated Intravascular Coagulation.

Disseminated intravascular coagulation (DIC) is induced by excess activation coagulation, and activated platelets are also involved in pathogenesis. Therefore, plasma levels of soluble C-type lectin-like receptor 2 (sCLEC-2), a new marker for platelet activation, can be expected as a marker of DIC in critically ill patients. Plasma levels of sCLEC-2 and D-dimer were measured using the STACIA system. Plasma sCLEC-2 and D-dimer levels were significantly higher in patients with underlying diseases of DIC than in those with unidentified clinical syndrome (UCS). Plasma sCLEC-2 levels were significantly higher in the patients with DIC and Pre-DIC than in those without DIC or Pre-DIC. Similarly, plasma D-dimer levels were also significantly higher in patients with DIC and Pre-DIC than in those without DIC or Pre-DIC. The plasma sCLEC-2 levels in all patients and those with a DIC score ≤ 4 were significantly higher in non-survivors than survivors. The plasma D-dimer levels in all patients, those with a DIC score ≥ 5 and those with a DIC score ≤ 4, were significantly higher in non-survivors than in survivors. The plasma sCLEC-2 is expected as a marker for DIC/Pre-DIC as well as the prognostic marker in critically ill patients.