Clinical Observation of Safety and Efficacy about Low-Molecular-Weight Heparin Prophylaxis for Venous Thromboembolism Following Gastrointestinal Tumor Surgery
|School||Hebei Medical University|
|Keywords||venous thromboembolism （VTE） deep veinthrombosis(DVT) prevention gastrointestinal tumor surgery perioperative|
Object:venous thromboembolism(VTE) is an importantcomplication after gastrointestinal tumor surgery, surgerns are payingmore and more attention on its prevention. And the way of usinglow-molecular-weight heparin (LMWH) to prevent VTE is graduallyaccepted. But the dosage and method of the drug has not come to thecommon view. At present, there are no prospective researches about thedosage of drug on VTE prophylaxis in our country yet, and also there isnot enough evidence. The determination of anti-Factor Xa can effectivelymonitor the activity of LMWH。This research is to monitor the activity ofanti-Factor Xa of two different dosage regimen by chromogenic substrateassay，and at the same time, we observe the safety and efficacy of VTEprophylaxis by different dosage regimen. So that we would provide someevidence based proof for VTE prevention after gastrointestinal tumorsurgeries.Methods:Randomly selected October2010to December2011postoperative patients who are at high or the highest risk of VTE40casesfrom gastrointestinal surgery in our hospital, which include24male casesand16female cases, is at a average age of55.9years (34~76years).Exclusion criteria:1.Younger than18years or older than80years;2.Seriously ill, or hepatic insufficiency or renalinsufficiency(Aspartate-aminotransferase (ALT) orAlanine-aminotransferase (AST) or creatinine or urea nitrogen is higherthan normal level);3.Anticoagulation contraindications, for example,active peptic ulcer disease, active hemorrhage, Infective endocarditis,accelerated hypertension [systolic pressure (SBP)>200mmHg or diastolic pressure (DBP)>120mmHg], cerebral hemorrhage with thepast3months;4.Blood coagulation disorders.40cases were randomlydivided into2groups,16cases in group A and24cases in group B. Allthe patients were given the LMWH prophylaxis for VTE12hours afteroperation(if the volume of abdominal drainage exceed200mL12hoursafter operation and was strong bloody ascites, then the start time could beextended to24hours after operation) after eliminating anticoagulationcontraindications. Group A were giver LMWH5000IU per24hours andgroup B wer given LMWH5000IU per12hours. All the patients’ bloodsamples were collected at the first day、second day and seventh day afteroperation,3.5hours after receiving LMWH. The2.7mL blood sampleswere immediately inject into3mL vacuum test tubes which contained0.109mol sodium citrate. and then centrifuged15minutes at the speed of3000r/min at the room temperatures, and then transfer the plasma toanother tube with pipettes. All the samples were stored at the lowtemperature of-80℃。We checked every case from the first day toseventh day after operation, checked whether there was tenderness alongthe deep vein, whether the legs were swelling, whether HomansSyndrome was positive, whether the patients had the symptom ofdyspnea、palpitation、chest pain or hemoptysis. If these symtoms appeared,took the d-dimer test immediately, if they did’t appeared, took thed-dimer test at the seventh day after operation［.if d-dimer≤300ug/L, VTEexcluded; if d-dimer>300ug/L， lower limb compression venousultrasonography（CUS） or arterial blood gas analysis(ABG) would betaken, and pulmonary artery CT would also be taken if necessarily］.Thecomplication of haemorrhage and platelet count were strictly monitored.Termination events:(1)any hemorrhagic complications, such as hematoma,abdominal bleeding and so on；（2） hepain inducedthrombocytopenia(HIT)；（3）deep vein thrombosis(DVT) confirmed byCUS and pulmonary embolism(PE) by pulmonary artery CT, the researchwould be stopped, and the standard treatment would be given.(4)allergy to LMWH. Finally, all blood samples were detected anti-FXa bychromogenic substrate assay. The recommended anti-FXa of3.5hoursafter injection was0.5-1.0IU/mL.Result:1In40cases,1case in group A suffered upper gastrointestinalhemorrhage, which was considered to be stress ulcer. The research wasimmediately stopped. This patient was cured after effective treatment, anddischarged well. This case was a gastric cancer patient, which tumorstaging was T2N0M0, and did the operation of standard D2gastrectomywith the anastomosis of Billroth Ⅱ. Therapeutic schedule：LMWH5000IU subcutaneous injection per12hours.2Abdominal drainage volume of72hours after operation: group Awas (96.69±31.99）mL，group B was (87.96±24.74）mL. The differencesbetween the two groups had no statistical significance(P>0.05). Afterrejecting the case of alimentary tract hemorrhage, there were no othercomplications.3D-dimer results: group A was（606.78±276.47）ug/L, group B was(621.25±226.85) ug/L, with no significant statistical difference. Therewere15cases (93.7%)in group A whose d-dimer was higher than300ug/L, and19cases (82.6%)in group B. There was no significantstatistical difference about the constituent ratio of twogroups(P>0.05).There was no VTE cases in this whole research.4Monitoring result of anti-FXa: in the first day, group A was(0.66±0.14)IU/mL, group B was (0.69±0.14)IU/mL; in the second day,group A was (0.68±0.14)IU/mL, group B was (0.69±0.07)IU/mL; in theseventh day, group A was (0.70±0.11)IU/mL, group B was(0.73±0.10)IU/mL. All the result was between0.5and1.0IU/mL whichwas the recommended blood concentration。There was no significantstatistical difference with two groups.5In the first day after operation, anticoagulation efficient of group Awas87.50%(14/16), with no cases’ anti-FXa greater than1.0IU/mL. Anticoagulation efficient of group B was95.65%(22/24),with one case’santi-FXa greater than1.0IU/mL, but with no bleeding complicationshappened to him. There was no significant statistical difference ofanticoagulation efficiency between two groups(P<0.05). In the secondday after operation, anticoagulation efficient of group A was93.75%(15/16), with no cases’ anti-FXa greater than1.0IU/mL.Anticoagulation efficient of group B was95.65%(22/24),with no case’santi-FXa greater than1.0IU/mL.There was no significant statisticaldifference of anticoagulation efficiency between two groups. In theseventh day, all the cases of two groups had achieved the effectiveanticoagulation, with one case’s anti-FXa greater than1.0IU/ml in groupA, but with no bleeding complications.Conclusion:Both of two regimens could achieve the effective anticoagulation3.5hours after injection, and with treatment’s going on until the seventhday after operation, there was no obvious pharmacodynamicaccumulation. The regimen of LMWH subcutaneous injected per24hours could prevent perioperative VTE effectively and safely. Theregimen of LMWH subcutaneous injected per12hours could also preventperioperative VTE effectively, but it may also increase the risk ofbleeding complications. It make no sense to monitor plasma d-dimer in7days after gastrointestinal tumor surgery.