{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:05:10Z","timestamp":1789110310747,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Health, Labour and Welfare of Japan.","award":["H30-015"],"award-info":[{"award-number":["H30-015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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)\u2013small-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 \u22648.0 \u00d7 1010\/L were significantly longer than those in patients with a platelet count &gt; 8.0 \u00d7 1010\/L and the peak heights of the CWA-sTF\/FIXa in patients with a platelet count of \u22648.0 \u00d7 1010\/L were significantly lower than those in patients with &gt;8.0 \u00d7 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.<\/jats:p>","DOI":"10.3390\/jcm10245987","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T04:23:47Z","timestamp":1640060627000},"page":"5987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clot Waveform Analysis Demonstrates Low Blood Coagulation Ability in Patients with Idiopathic Thrombocytopenic Purpura"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-8633","authenticated-orcid":false,"given":"Hideo","family":"Wada","sequence":"first","affiliation":[{"name":"Department of Laboratory and General Medicine, Mie Prefectural General Medical Center, Yokkaichi 510-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuko","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, Mie Prefectural General Medical Center, Yokkaichi 510-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Ezaki","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, Mie Prefectural General Medical Center, Yokkaichi 510-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Mie Prefectural General Medical Center, Yokkaichi 510-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Moritani","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Mie Prefectural General Medical Center, Yokkaichi 510-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Mie University Graduate School of medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Mie University Hospital, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Masuya","sequence":"additional","affiliation":[{"name":"Course of Nursing Science, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-9422","authenticated-orcid":false,"given":"Isao","family":"Tawara","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Mie University Graduate School of medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Shimpo","sequence":"additional","affiliation":[{"name":"Mie Prefectural General Medical Center, Yokkaichi 510-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Shimaoka","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1055\/s-0039-1700512","article-title":"Immune thrombocytopenia in adults: Modern approaches to diagnosis and treatment","volume":"46","author":"Kuter","year":"2020","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Terrell, D.R., Neunert, C.E., Cooper, N., Heitink-Poll\u00e9, K.M., Kruse, C., Imbach, P., K\u00fchne, T., and Ghanima, W. (2020). Immune thrombocytopenia (ITP): Current limitations in patient management. Medicina, 56.","DOI":"10.3390\/medicina56120667"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1182\/blood.2019003599","article-title":"Identifying and treating refractory ITP: Difficulty in diagnosis and role of combination treatment","volume":"135","author":"Miltiadous","year":"2020","journal-title":"Blood"},{"key":"ref_4","first-page":"e9083","article-title":"Immune thrombocytopenia purpura secondary to COVID-19","volume":"12","author":"Bennett","year":"2020","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.thromres.2020.06.018","article-title":"Effects of platelet and phospholipids on clot formation activated by a small amount of tissue factor","volume":"193","author":"Wada","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1076029620912027","DOI":"10.1177\/1076029620912027","article-title":"Update on the Clot Waveform Analysis","volume":"26","author":"Wada","year":"2020","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1055\/s-0037-1613023","article-title":"The utility of activated partial thromboplastin time (aPTT) clot waveform analysis in the investigation of hemophilia A patients with very low levels of factor VIII activity (FVIII:C)","volume":"87","author":"Shima","year":"2002","journal-title":"Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1182\/blood.V100.7.2522","article-title":"Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation","volume":"100","author":"Toh","year":"2002","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s12185-016-2108-x","article-title":"A combined approach using global coagulation assays quickly differentiates coagulation disorders with prolonged aPTT and low levels of FVIII activity","volume":"105","author":"Matsumoto","year":"2017","journal-title":"Int. J. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tokutake, T., Baba, H., Shimada, Y., Takeda, W., Sato, K., Hiroshima, Y., Kirihara, T., Shimizu, I., Nakazawa, H., and Kobayashi, H. (2016). Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157835"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1177\/1076029617724230","article-title":"An Evaluation of the Activated Partial Thromboplastin Time Waveform","volume":"24","author":"Matsumoto","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12959-019-0201-0","article-title":"Usefulness of the APTT waveform for the diagnosis of DIC and prediction of the outcome or bleeding risk","volume":"17","author":"Suzuki","year":"2019","journal-title":"Thromb. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/ijlh.12727","article-title":"Monitoring of hemostatic abnormalities in major orthopedic surgery patients treated with edoxaban by APTT waveform","volume":"40","author":"Hasegawa","year":"2018","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1076029620976913","DOI":"10.1177\/10760296211012094","article-title":"The evaluation of hemostatic abnormalities using a CWA-small amount tissue factor induced FIX activation assay in major orthopedic surgery patients","volume":"27","author":"Hasegawa","year":"2021","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.thromres.2021.03.030","article-title":"Evaluation of hemostatic abnormalities in patients who underwent major hepatobiliary pancreatic surgery using activated partial thromboplastin time-clot waveform analysis","volume":"201","author":"Maeda","year":"2021","journal-title":"Thromb. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1182\/blood-2017-03-754119","article-title":"Clinical updates in adult immune thrombocytopenia","volume":"129","author":"Lambert","year":"2017","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wada, H., Ichikawa, Y., Ezaki, E., Matsumoto, T., Yamashita, Y., Shiraki, K., Shimaoka, M., and Shimpo, H. (2021). The reevaluation of thrombin time using a clot waveform analysis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10214840"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/09537104.2020.1727871","article-title":"Novel scientific approaches and future research directions in understanding ITP","volume":"31","author":"Hicks","year":"2020","journal-title":"Platelets"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1055\/s-0028-1104546","article-title":"Standardization and clinical utility of thrombin-generation assays","volume":"34","author":"Berntorp","year":"2008","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1055\/s-0030-1265295","article-title":"Thrombin generation testing for monitoring hemophilia treatment: A clinical perspective","volume":"36","author":"Salvagno","year":"2010","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1055\/s-0040-1718373","article-title":"The Use of Recombinant Activated Factor VII in Patients with Glanzmann\u2019s Thrombasthenia","volume":"121","author":"Poon","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/ijlh.13302","article-title":"Thrombin generation abnormalities in Quebec platelet disorder","volume":"42","author":"Brunet","year":"2020","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/trf.16179","article-title":"Factor V activity in apheresis platelets: Implications for management of FV deficiency","volume":"61","author":"Gupta","year":"2021","journal-title":"Transfusion"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100774","DOI":"10.1016\/j.blre.2020.100774","article-title":"Hemostatic changes by thrombopoietin-receptor agonists in immune thrombocytopenia patients","volume":"47","author":"Brandwijk","year":"2021","journal-title":"Blood Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1080\/09537104.2019.1639655","article-title":"Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists","volume":"31","author":"Garabet","year":"2020","journal-title":"Platelets"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kobayashi, M., Wada, H., Fukui, S., Mizutani, H., Ichikawa, Y., Shiraki, K., Moritani, I., Inoue, H., Shimaoka, M., and Shimpo, H. (2021). A Clot Waveform Analysis Showing a Hypercoagulable State in Patients with Malignant Neoplasms. J. Clin. Med., 10.","DOI":"10.3390\/jcm10225352"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/24\/5987\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:50:08Z","timestamp":1760169008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/24\/5987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":26,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["jcm10245987"],"URL":"https:\/\/doi.org\/10.3390\/jcm10245987","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}