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

Yamamoto, Akira; Wada, Hideo; Ichkawa, Yuhuko; Tanaka, Motoko; Tashiro, Haruhiko; Shiraki, Katsuya; Shimpo, Hideto; Yamashita, Yoshiki; Mastumoto, Takeshi; Shimaoka, Motomu; Iba, Toshiaki; Suzuki‐Inoue, Katsue

doi:10.3390/jcm10132860

Cited by 19 publications

(19 citation statements)

References 22 publications

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“…Therefore, large-scale studies are required to confirm the usefulness of this quick DIC score system for the diagnosis of DIC and pre-DIC. Regarding the survival of patients assessed using the quick DIC score system, approximately 50% of the patients diagnosed with possible DIC died, suggesting that the quick DIC score may predict poor outcomes as DIC patients still show poor outcomes and DIC is one of the most important causes of death in critical ill patients [3,16].…”

Section: Discussionmentioning

confidence: 99%

Proposal of Quick Diagnostic Criteria for Disseminated Intravascular Coagulation

Wada

Yamamoto

Tomida

et al. 2022

JCM

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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.

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Section: Discussionmentioning

confidence: 99%

Proposal of Quick Diagnostic Criteria for Disseminated Intravascular Coagulation

Wada

Yamamoto

Tomida

et al. 2022

JCM

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“…It was reported that the mean plasma concentration of these soluble forms of CLEC-2 was 59-100 pg/mL in healthy volunteers and was increased to 260-380 pg/ml in patients with platelet-activating diseases 22 . In some patients with thrombotic microangiopathy or disseminated intravascular coagulation, the concentration of soluble CLEC-2 exceeds 1000 pg/ml [30][31][32] . Because platelets are retained in in amed glomerular capillaries 33 , the local concentration of soluble CLEC-2 may be higher in glomerular diseases.…”

Section: Discussionmentioning

confidence: 99%

C-type lectin-like receptor (CLEC)-2, the ligand of podoplanin, induces morphological changes in podocytes

Tanaka

Watanabe

et al. 2022

Preprint

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Podoplanin (PDPN) is intensely expressed on the podocyte membrane in an evolutionally conserved manner. CLEC-2, the endogenous ligand of PDPN, is highly expressed in platelets and also exists in a soluble form in plasma. Normally, podocytes are sequestered from CLEC-2, but when the glomerular barrier is injured, podocytes gain access to CLEC-2. We tested the effects of CLEC-2 in podocytes in vitro and in vivo. Cultured podocytes treated with Fc-CLEC-2 demonstrated that CLEC-2 induced the dephosphorylation of moesin, which we found to be the major ERM in cultured podocytes. Podocytes treated with Fc-CLEC-2 also showed the dissociation of F-actin filaments from PDPN, F-actin degradation, detachment, and round morphology. Next, we perfused normal mouse kidney in vivo with FLAG-CLEC-2. CLEC-2 induced dephosphorylation of ezrin and widening of the foot processes of podocytes. Platelets were detected by immunostaining for CD41 in the urine of mice with podocyte injury, indicating that podocytes can encounter platelets when glomeruli are injured. Collectively, these observations suggest that when platelets leak through the injured glomeruli, CLEC-2 from the platelets acts on PDPN in podocytes and induces morphological change and detachment, which may further aggravate podocyte injury. Thus, PDPN on podocytes may work as a leaked-platelet sensor.

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“…COVID-19 infection was diagnosed by polymerase chain reaction using the Gene expert system (Cepheid, CA, USA). We measured the plasma sCLEC-2 levels via chemiluminescent enzyme immunoassay (CLEIA) using previously described monoclonal antibodies and the STACIA CLEIA system (LSI Medience, Tokyo, Japan) [17,19]. In brief, magnetic particles were coated with the anti-CLEC-2 monoclonal antibody 11D5.…”

Section: Methodsmentioning

confidence: 99%

“…Soluble C-type lectin-like receptor 2 (sCLEC-2) has been introduced as a new biomarker of platelet activation [15]. Elevated plasma levels of sCLEC-2 have been reported in patients with thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC) [16,17], as well as in patients with acute coronary syndrome [18] or acute cerebral infarction [19].…”

Section: Introductionmentioning

confidence: 99%

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

Wada

Ichikawa

Ezaki

et al. 2022

JCM

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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.

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

Cited by 19 publications

References 22 publications

Proposal of Quick Diagnostic Criteria for Disseminated Intravascular Coagulation

Proposal of Quick Diagnostic Criteria for Disseminated Intravascular Coagulation

C-type lectin-like receptor (CLEC)-2, the ligand of podoplanin, induces morphological changes in podocytes

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

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