- 學位論文
以血漿FMC、D-Dimer、FDP和Fibrinogen凝血相關檢驗項目作為白血病患發生瀰漫性血管內栓塞或出血之危險性評估
The clinical significance of plasma FMC, D-Dimer, FDP and Fibrinogen level for risk assessment of disseminated intravascular coagulation or hemorrhage in leukemia patients.
摘要
研究背景: 出血和血栓形成是白血病患者早期死亡的主要危險因素，化療也增加了這兩種併發症的可能性。白血病患者即使沒有活動性血栓形成和/或出血，但通常有凝血機制過度活化的狀態或伴隨有慢性瀰漫性血管內凝血的證據。而白血病細胞毒性治療或感染是急性白血病中凝血機制激活的主要因素，臨床表徵從局部靜脈或動脈血栓形成到擴散並危及生命的出血。顯示凝血機制的監控確實能反映患者出血或血栓形成時機。 研究目的: 本研究將探討白血病患者血漿中Fibrin monomer complex(FMC)、D-Dimer、FDP、Fibrinogen濃度的變化與瀰漫性血管內栓塞或出血之臨床相關性，提供輔助性療效觀察及預後評估之指標。 研究方法: 將收集2017年7月1日至2018年6月30日期間，目標以國立台灣大學附設醫院雲林分院已確診為白血病之病患為實驗組對象，對照組為臨床健康者。收集臨床參數將包含性別、年齡、白血病疾病分類，樣本採集後經離心處理，分離取其血漿進行凝血檢驗項目Prothrombin Time(PT)、A.P.T.T、D-Dimer、Fibrinogen、FDP、FMC分析，收集數據並利用SPSS統計軟體進行統計分析。 成果: 本實驗結果分析60位受試者，經前瞻性臨床統計分析將可於白血病患者血漿中進一步比較Fibrin monomer、D-Dimer、FDP、Fibrinogen濃度的變化與白血病併發出血及血栓的相關性。白血病患者的凝血因子檢查具有異常顯著差異。白血病患者發現FDP與D-Dimer間具有顯著關聯性（p < 0.05）。利用log-rank test進行實驗組與對照組兩組間存活曲線的檢定，並畫出存活曲線圖（Kaplan-Meier curve），所得p =0.017，達到統計上顯著，故FDP濃度在兩組之間存活率有顯著差異。最後，利用ROC curve分析方法得到AUC（Area Under Curve），以FDP所得到的曲線下面積最高（AUC：0.986）。 結論：因此，以凝血功能項目FDP濃度用於評估預測造成出血或栓塞之危險性是最佳工具，進而推廣作為白血病患者病情進展、療效觀察及預後評估之指標。
並列摘要
Background: Hemorrhage and thrombosis are the major risk factors for early death in leukemia patients, and chemotherapy also increases the probability of both complications. Patients with leukemia often present with a hypercoagulable state or chronic disseminated intravascular coagulation, even in the absence of active thrombosis and/or hemorrhage. Aberrant activation of the coagulation cascade play an important role in the infection mechanism or treatment strategies, and clinical features showed that local venous or arterial thrombosis to disseminated even life-threatening hemorrhage. Previous evidences indicated that monitoring of the coagulation mechanism does reflect the patient's bleeding or thrombotic timing. Aim: Here we will investigate the main laboratorial findings in plasma Fibrin monomer (FMC), D-Dimer, FDP, Fibrinogen level and integrate the clinical relevance of disseminated intravascular embolization or hemorrhage, and to provide adjunctive efficacy observation and prognostic evaluation . Materials and methods: From July 1, 2017 to June 30, 2018, the patients who have been diagnosed as leukemia by National Taiwan University Hospital Affiliated to Yunlin Hospital will be selected as the experimental group, and the control group as the clinical healthy subjects. The clinical parameters including sex, age and leukemia classification. The samples will be collected and centrifuged, and the plasma samples willbe collected for prothrombin time (PT), APTT, D-Dimer, Fibrinogen, FDP and FMC test. In addition, SPSS statistical software will be used for statistical analysis. Outcome: We analyzed data for 60 patients. The prospective clinical statistical analysis will be able to further compare the plasma Fibrin monomer, D-Dimer, FDP, Fibrinogen level with leukemia complicated by hemorrhage and thrombosis. Coagulation factor test in leukemia patients has significant differences. There is a significant correlation between plasma FDP and D-Dimer level in patients with leukemia（p < 0.05）.Kaplan–Meier curves showing the association between the experimental group and the control group, the FDP level has a significant difference in survival between the two groups（Log-rank p=0.017）. Finally,in the receiver operating characteristic curve analysis, FDP level had the largest area under the curve (AUC; 0.986). Conclusions: Therefore, assessing FDP level in coagulation function is the best tool to predict the risk of bleeding or embolism . Furthermore, this findings of study will be apply for early prediction and evaluation of therapeutic effect in leukemia patients with coagulated disorder.