Detection of Prethrombotic State Malignant Neoplasms, Including Pancreatic Cancer, Using Clot Waveform Analysis

Mayu Kobayashi, Hideo Wada, S. Fukui, Yasuaki Shimada, Yuuichi Nakazawa, Hiroki Mizutani, Y. Ichikawa, Yuuki Nishiura, I. Moritani, Yutaka Yamanaka, Hidekazu Inou, M. Shimaoka, Hideto Shimpo, K. Shiraki
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Abstract

Background: Cancer, especially pancreatic cancer, is frequently associated with thrombosis which is one of the causes of poor outcomes; moreover hypercoagulability can be present in cancer patients. Hypercoagulability is considered to be caused by a thrombin burst. Methods: Activated Partial Tthromboplastin Time (APTT), small amount of tissue factor induced FIX activation assay (sTF/FIXa) and Thrombin Time (TT) assessment using Clot Waveform Analysis (CWA) were performed in 138 patients with malignant neoplasms, including pancreatic cancer. Results: The first derivative peak (1st DP) time (1st DPT), 1st DP height (1st DPH) and 1st DPH/1st DPT ratio were increased in a clotting-factor-FVIII-dependent manner. Thrombosis was frequently associated with pancreatic cancer and was observed in the early stage. CWA-APTT and CWA-sTF/FIXa indicated that the peak times and heights were markedly longer and higher, respectively, in cancer patients, especially pancreas cancer patients, than in patients without cancer. The 1st DPH/1st DPT ratios of CWA-sTF/FIXa were significantly high in patients with pancreas cancer (median value 1.5). CWA-TT showed that the peak times were significantly shorter in cancer patients than in healthy volunteers and that the peak heights were significantly higher in cancer than in benign pancreas diseases. The cutoff value of the 1st DPH/ 1st DPT of sTF/FIXa for cancer patients with thrombosis vs. all patients without cancer was 1.3. Conclusions: Cancer patients, including those with pancreatic cancer were frequently associated with thrombosis due to hypercoagulability caused by thrombin burst detected by CWA. A high 1st DPH/1st DPT ratio of sTF/FIXa may suggest an association with cancer or thrombosis.
利用血栓波形分析检测血栓前状态恶性肿瘤,包括胰腺癌
背景:癌症,尤其是胰腺癌,经常与血栓形成有关,而血栓形成是导致预后不良的原因之一;此外,癌症患者还可能出现高凝状态。高凝状态被认为是由凝血酶猝灭引起的。方法:对 138 名恶性肿瘤(包括胰腺癌)患者进行活化部分凝血酶原时间(APTT)、少量组织因子诱导 FIX 活化测定(sTF/FIXa)和凝血酶时间(TT)评估,并使用凝块波形分析法(CWA)进行评估。结果显示第一导数峰(1st DP)时间(1st DPT)、第一导数峰高(1st DPH)和第一导数峰高/第一导数峰高比值均呈凝血因子-FVIII依赖性增加。血栓形成经常与胰腺癌有关,并且在早期就能观察到。CWA-APTT和CWA-sTF/FIXa表明,癌症患者,尤其是胰腺癌患者的峰值时间和峰值高度分别明显长于非癌症患者。在胰腺癌患者中,CWA-sTF/FIXa 的第 1 DPH/1st DPT 比值明显偏高(中位值为 1.5)。CWA-TT 显示,癌症患者的峰值时间明显短于健康志愿者,癌症患者的峰值高度明显高于良性胰腺疾病患者。与所有非癌症患者相比,血栓形成癌症患者 sTF/FIXa 的第一 DPH/ 第一 DPT 临界值为 1.3。结论癌症患者,包括胰腺癌患者,经常会因 CWA 检测到的凝血酶猝灭引起的高凝血功能而导致血栓形成。sTF/FIXa 的第 1 DPH/1st DPT 比值较高可能与癌症或血栓形成有关。
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