A Clinical Study of Malignant Hypercoagulable State and Intervention
|School||Hebei Medical University|
|Keywords||venous thromboembolism cancer hypercoagulable state preventive anticoagulant therapy LMWH recurrence and metastasis prognosis|
Objective: Malignant tumor is often associated with venousthromboembolism (Venous Thromboembolism,VTE), the risk of itsoccurrence is seven times that of the general population, and accompanied bythe entire disease process. VTE including deep venous thromboembolism(Deep Venous Thrombosis, DVT), pulmonary embolism (PulmonaryEmbolism, PE), etc. The VTE is closely related to the morbidity and mortalityof cancer patients, and seriously affect the quality of life. Thrombosis occurredin hematological based hypercoagulable state of malignancy.The tumor itselffactors, treatment-related factors and other factors together led the thehypercoagulable state’s formation. Hypercoagulable state is associated withtumor recurrence and metastasis.By the rational use of preventiveanticoagulant drugs on cancer patients, VTE is largely avoided.In this study,370malignant tumor patients (including18patients withVTE) received treatment in the Fourth Hospital of Hebei Medical University,Department of Medical Oncology. Analysing the information of patients’clinical data,laboratory testing,prognosis,evaluation,treatment and understan-ding hypercoagulability laboratory diagnosis. Having been merged VTE incancer patients, exploring its rationalization treatment method andprophylactic anticoagulation status to provide a reference for patients withmalignant disease about prevention and treatment of VTE.Methods: In this study, clinical data were collected from370cases ofhospitalized patients with malignant tumors (including18patients with VTEpatients) in February2010to December2012in the Fourth Hospital of HebeiMedical University, Department of Medical Oncology. Stratified analyzing tounconsolidated VTE patients,comparing different points the coagulation statusand D-dimer differences.Analyzing the clinical data of the combined VTE patients and understanding their incidence the hypercoagulable statehematology foundation, diagnosis, treatments, risk factors and prognosis;Meanwhile,to explore prophylactic anticoagulation status.Diagnosis of DVT:Venous Doppler ultrasound diagnose methodcombined with the patient’s clinical symptoms; The gold standard diagnosis ofPE is CT pulmonary angiography (CT Pulmonary Angiography CTPA);Diagnosis of catheter-related thrombosis include placement history of venouscatheter, the corresponding partsclinical manifestations and venous Dopplerultrasound diagnosis. Its efficacy evaluation is divided into cured, effectiveand invalid.Unconsolidated VTE patients received preventive anticoagulant treatmentwith Nadroparin Calcium5000u, subcutaneous injection of1/12h orDalteparin Sodium5000u subcutaneous injection of1/12h or oral aspirin0.1g/day or warfarin oral, in accordance with the international normalized ratio(International Normalized Ratio, INR) value to adjust the dose. VTE patientstreatments include general treatment, while giving the low molecular weightheparin or warfarin therapy.The main mode of follow-up included the phone,out-patient andin-patient.All patients were followed up until December31,2012. Establishinga database of all clinical data and analysising date by the application of SPSS13.0statistical software.Measurement data were described as mean±standarddeviation, count data using χ2test;To multivariate analysis by Logisticregression, survival curves were plotted using the Kaplan-Meiermethod.Application COX regression model analysed a variety of factors onthe survival, P<0.05was considered statistically significant.Results:1Different gender patients of coagulation and D-dimer had nosignificant differences (P>0.05); Patients≥60years of age and＜60years ofage whose D-dimer and FIB had no significant differences (P>0.05);Compared to Squamous cell carcinoma, Adenocarcinoma patients ofAPTT values reduced and FIB elevated; Lymph node metastasis (N1-3) patientscompared patients with lymph node metastases (N0) D-dimer elevated; Ⅲ-Ⅳ s tage patients comparedⅠ-Ⅱ s tage,FIB elevated,but APTT reduced.Different groups of Lung cancer, stomach cancer,esophageal cancer, breastcancer,colorectal cancer,pairwise comparisons between groups,the differencewas not statistically significant;tumor-bearing group compared with thenon-tumor-bearing group,D-dimer and FIB in patients with tumor significantlyelevated (P<0.01) and APTT values decreased (P<0.05).There was astatistically significant difference,but PT,TT had no significantdifference;After anticoagulant treatment than before anticoagulant therapy,D-dimer, TT had no significant change (P>0.05), while PT values prolonged,APTT shortened and FIB values significantly reduced (P<0.05).2The group of malignant tumor thrombosis incidence rate was4.9%.Thrombotic group compared with non-thrombotic group, thrombosisgroup in later clinical stage (P=0.046), age, gender, metastatic sites had nosignificant difference.3Comparing with non-thrombotic group,D-dimer,PT,FIB in thrombosisgroup increased.The thrombosis group of APTT,TT had lower values,whichhad a statistically significant difference.4Non-thrombotic patients and thrombosis group of patients OS had nosignificantly differences,P=0.69;Non-thrombotic patients PFS was alsosignificantly longer than the thrombosis group of patients, P=0.002.517patients with venous thrombosis confirmed by ultrasound and was5%of the total number of cases.9cases of17patients with DVT wereasymptomatic patients, venous ultrasound detection of asymptomatic DVTpositive rate was52.9%.6All patients underwent antithrombotic therapy combined withanti-tumor therapy,more than half (77.8%) of patients could benefit fromanticoagulant therapy combined with anti-cancer therapy;Within6to12months after the diagnosis of malignancy and within7to12postoperative theprobability of occurrence of thrombosis had increased.7Single factor analysis showed that patients with granulocytecolony-stimulating factor treatment (P=0.049) and catheter treatment (P= 0.007) were thrombosis related risks and that was considered statisticallysignificant.Other factors had no significant effect.Multi-factor regressionanalysed results and showed that granulocyte colony-stimulating factortreatment and catheter treatment eventually into the regression equation.Theywere the independent factors affecting thrombosis.8The clinical intervention rate of preventive anticoagulant therapy was77%.The incidence of thrombosis of intervention group was3.8%,non-intervention group was10.8%.The incidence of thrombosis inintervention group than non-intervention group decreased.The difference wasstatistically significant (P<0.05);Warfarin group had higher incidence ofadverse reactions, accounting for57.1%,while LMWH lower,for5.5%.9Compare the intervention group with the non-intervention group,OSLog Rank test χ2=4.698, P=0.03.The intervention group OS was longer thanthe non-intervention group;PFS was no significant difference between theintervention group and the non-intervention group (P=0.58); COX risk modelanalysed that covariates (whether metastasis)(P=0.005) influenced the OS,the relative risk of20.387.10Groups of Nadroparin Calcium and Dalteparin Sodium had nosignificant differences of OS and PFS.11The total number of placed venous catheter was68.1%,butcatheter-related thrombosis did not occur in patients.77.8%of patients placedcatheter received prophylactic anticoagulation.Most patients with prophylacticanticoagulation were multi-hospital chemotherapy patients, indicating a higherrate of prophylactic anticoagulation.Conclusion:1Hypercoagulability factors in patients with malignanttumors included adenocarcinoma, lymph node metastasis, late TNM stage andtumor status.Anticoagulant therapy could improve the hypercoagulable state.2Malignant tumor thrombosis incidence rate was4.9%.Its median agewas61.6years.61.1%patients were Ⅲ-Ⅳ stage.Many patients withthrombosis were in the late stages of the disease and had a higher rate ofclinical metastasis.They had short disease progression time and poor prognosis.3Malignant patients merged VTE had hypercoagulable state and couldbenefit from the anticoagulant combination with chemotherapy treatment.4Doctors could not diagnosis DVT just by observing clinical symptomsfor patients. With asymptomatic DVT patients,venous ultrasound couldimprove the positive rate of thrombosis. Venous ultrasound should beconsidered as one of the routine testing of cancer patients.5The granulocyte colony-stimulating factor treatment and cathetertreatment closely related to thrombosis,were dependent risk factors affectingthrombosis.6The group of clinical intervention rate of preventive anticoagulanttherapy was77%.The rate of thrombosis was3.8%.Hospitalized cancerpatients could benefit from prophylactic anticoagulation by LMWH.7Anticoagulant therapy prolonged the survival period, but whetherspread was the main factor to influence the survival time of patients.8Patients with Nadroparin Calcium and Dalteparin Sodium had nosignificant impact on PFS、OS.Due to different pharmacological effects,cross-use was not recommended. LMWH had less adverse reactions.9The catheter patients prophylactic anticoagulation was not routinelyrecommended. In view of the complexity of the catheter patients, it should beanalyse specificly.