Anti-Xa Levels in Bariatric Surgery Patients Receiving Prophylactic Enoxaparin

Background Limited data exist regarding efficacy and dosing of low-molecular-weight heparins, including enoxaparin, for morbidly obese patients. Prophylactic doses of 30 to 60 mg every 12 h have been described in bariatric surgery patients with appropriate anti-Xa levels reported between 0.18 and 0.6 units/mL. Methods Fifty-two laparoscopic gastric bypass or banding patients were enrolled. Patients were divided into two groups by the dose of enoxaparin that was given: Group 1—enoxaparin 30 mg every 12 hours—and Group 2—enoxaparin 40 mg every 12 h. Anti-Xa levels were obtained 4 h after the first and third doses. Levels between 0.18–0.44 units/mL were considered appropriate. Results There were 19 patients (74% female, mean body mass index [BMI] 48.4 kg/m²) in Group 1 and 33 patients (82% female, mean BMI 48.5 kg/m²) in Group 2. In Group 1, anti-Xa levels were 0.06 and 0.08 units/mL after the first and third doses, respectively. In Group 2, anti-Xa levels were 0.14 and 0.15 units/mL after first and third doses, respectively (p = NS). There was a statistically significant difference in anti-Xa levels between Group 1 first dose and Group 2 first dose (p < 0.05) and between Group 1 third dose and Group 2 third dose (p < 0.05). Percentage of appropriate anti-Xa levels at first dose differed 0% vs. 30.8% (Group 1 vs. Group 2; p = 0.01) and at third dose 9.1% vs. 41.7% (Group 1 vs. Group 2; p = 0.155). Conclusion When prophylactic dose enoxaparin of 30 mg every 12 h was changed to 40 mg every 12 h in bariatric surgery patients, anti-Xa levels significantly increased with prophylactic dose enoxaparin in bariatric surgery patients. The percentage of appropriate levels also increased; however, more than half of the patients receiving 40 mg every 12 hours failed to reach therapeutic levels. No levels were supratherapeutic. Dosage of 40 mg every 12 h may not be sufficient for bariatric surgery patients. Presented at the Society of American Gastrointestinal Endoscopic Surgeons annual meeting; April 18–22, 2007; Las Vegas, NV.     

依诺肝素0.75 mg/kg动脉推注在冠状动脉造影和介入术中的应用

目的在中国人群中评价冠状动脉（冠脉）造影和经皮经腔冠脉介入术（PCI）中应用依诺肝素0．75mg／kg经动脉鞘管注射抗凝的安全性及有效性。方法160例择期PCI术患者随机分为两组,依诺肝素组给予依诺肝素0．75mg／kg,手术时间超过90min者再给0．3mg／kg;普通肝素组给予普通肝素100U／kg。结果注射依诺肝素后2h内,患者血浆抗Xa因子水平在0．5IU／ml以上。补充依诺肝素后可使所有患者血浆抗Xa因子水平4h内维持于0．5IU／ml以上。依诺肝素组鞘管内血栓发生率明显高于普通肝素组（26．6％比10．0％,P〈0．001）。两组30d内不良临床事件和出血事件发生率相似。结论择期PGI术中应用依诺肝素0．75mg／kg经动脉鞘管弹丸式注射进行抗凝是安全和有效的,有效抗凝强度至少可维持2h,手术时间超过2h的患者应补充依诺肝素。     

Hematopoietic stem cell transplantation for Hodgkin’s disease in a patient with dysfibrinogenemia and thrombosis

Introduction Dysfibrinogenemia is a disorder of fibrinogen structure and is associated with a functional abnormality. Since fibrinogen is a key component of both the procoagulant and fibrinolytic pathways, defects in fibrinogen function can be associated with increased risk for both hemorrhage and thrombosis. Management of patients with dysfibrinogenemia and a thrombotic tendency usually involves long-term anticoagulation. Case A 36-year-old male with relapsed nodular sclerosing Hodgkin’s was found to have a prolonged prothrombin time, low fibrinogen activity and a normal fibrinogen antigen during evaluation for a hematopoietic peripheral blood stem cell transplant. His past medical history was significant for an acute myocardial infarction and two episodes of acute pancreatitis. His father had dysfibrinogenemia complicated by multiple thrombotic episodes. A trans-esophageal echocardiogram revealed two thrombi, one each in the superior vena cava and the descending aorta. He was treated with enoxaparin and received peripheral blood stem cell transplantation. An effort was made to maintain his fibrinogen activity levels at 200 mg/dL using cryoprecipitate. A month following the transplant he developed a new thrombus in the right internal jugular vein, while on enoxaparin and he was started on argatroban and cryoprecipitate followed by fondaparinux. A repeat echocardiogram six weeks later demonstrated that the burden of thrombus both in the right atrium and descending aorta was significantly lower. Discussion This is the first case report of a patient with dysfibrinogenemia undergoing peripheral blood stem cell transplantation. Conventional anticoagulant therapy and cryoprecipitate seem to be a reasonable management strategy to prevent thrombosis in a patient with dysfibrinogenemia and a thrombophilic tendency. Secondly, fondaparinux can be used in cases of failure of therapy with low molecular weight heparins and may actually be superior to low molecular weight heparins, especially in patients with dysfibrinogenemia.     

利伐沙班对骨科大手术后深静脉血栓预防作用的研究进展

骨科手术后深静脉血栓发病率高,目前尚缺乏一种特别有效地预防方法.利伐沙班是一种直接凝血因子Xa抑制剂,为口服药物,对骨科术后深静脉血栓的预防作用较依诺肝素更强.本文就利伐沙班抗凝的作用机制、药动学、药物相互作用以及在骨科大手术后抗凝中的应用作一综述.     

The use of a HEMOCHRON® JR. HEMONOX™ point of care test in monitoring the anticoagulant effects of enoxaparin during interventional coronary procedures

Background: Enoxaparin is increasingly used for the anticoagulation of patients undergoing percutaneous coronary intervention (PCI). Several reports have suggested the utility of using point of care tests in monitoring the anticoagulation levels of enoxaparin in patients undergoing PCI. The objective of this study was to evaluate a new point-of-care test (POCT) HEMONOX? in monitoring the anticoagulant effect of enoxaparin in non citrated fresh whole blood samples from patients undergoing elective PCI procedure. Methods: Following IRB approval, blood samples were obtained from fifty-four patients who received two sequential intravenous doses of enoxaparin; 0.1 mg/kg followed 5 min later by 0.4 mg/kg for a total of 0.5 mg/kg. Blood was drawn at baseline and at 5, 10, 30 and 60 min post first bolus for evaluation in the clot-based POCT HEMONOX, ACT and aPTT and the chromogenic anti-Xa activity assay. Results: HEMONOX clotting time (CT) at baseline was 62.6 ± 6.2 secs, (n = 32) in healthy donors and statistically higher in PCI patients (71.6 ± 9.1 secs, p = 0.0001). The peak HEMONOX response that was always achieved at 10 min post bolus was >100 secs in all 54 patients, of these 83% yielded CT >150 secs (range: 150–466). There was no detectable anti-Xa activity level at baseline while peak HEMONOX CT corresponded to therapeutic levels (0.85 ± 0.14 U/ml; range: 0.61–1.34). Both HEMONOX CT and anti-Xa level significantly decreased at the time of sheath removal. HEMONOX CT at peak response suggested 3 patient subgroups with different levels of sensitivity to enoxaparin: low, intermediate and high responders. The correlation between anti-Xa activity level and HEMONOX CT was ≥0.85 in each patient subgroup when data from the 3 critical time points; baseline (absence of drug), peak response (10 min post bolus) and sheath removal (60 min post bolus) were analyzed. The correlation diminished to ≥0.83 when the analyses included data from all 5 time points [baseline, 5, 10, 30, and 60 min post bolus]. The HEMONOX test was the most sensitive POCT to measure the anticoagulant effects of enoxaparin. All patients completed PCI successfully. Conclusion: The HEMONOX test may be able to guide anticoagulation with enoxaparin during PCI.     

Best Poster Award. A comparison of thromboembolic and bleeding events following laparoscopic gastric bypass in patients treated with prophylactic regimens of unfractionated heparin or enoxaparin

INTRODUCTION: We prospectively evaluated 30-day thromboembolic and bleeding events in 2 groups of laparoscopic gastric bypass patients receiving different anticoagulation regimens. METHODS: The first cohort of patients received enoxaparin 40 mg subcutaneously preoperatively, 40 mg subcutaneously on postoperative day 0, and twice daily until discharge. The second cohort of patients received unfractionated heparin 5,000 units subcutaneously preoperatively, nothing on postoperative day 0, and 5,000 units 3 times per day until discharge. RESULTS: The incidence of deep venous thrombosis in both cohorts was 0. There was 1 pulmonary embolism in the heparin cohort (P = .999). Fourteen patients (5.9%) in the enoxaparin cohort required postoperative transfusions compared with 3 patients (1.3%) in the heparin cohort (P = .011). Four patients (1.7%) in the enoxaparin cohort required re-exploration for bleeding. CONCLUSION: Both enoxaparin and heparin are effective at preventing thromboembolic events following laparoscopic gastric bypass. Heparin is the preferred agent due to the excessive bleeding complications encountered with enoxaparin.     

Different effects of enoxaparin and unfractionated heparin on some thrombogenesis markers during hemodialysis: a cross-over study

Background

Unfractionated heparin (UFH) and low molecular weight heparin constitute fundamental anticoagulants during hemodialysis (HD). We aimed to investigate the effect of UFH and enoxaparin on plasma levels of prothrombin fragment 1 + 2 (PF 1 + 2) and thrombin/antithrombin complex (TAT) as markers of intravascular thrombogenesis during HD.

Methods

We enrolled 22 chronic HD patients, who were randomly assigned to either iv enoxaparin (n = 11) or UFH (n = 11) anticoagulation, and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. Plasma levels of PF 1 + 2 and TAT were measured by immunoassay at the start, at 10 and 180 min of HD session after each period of evaluation.

Results

The baseline PF 1 + 2 and TAT levels were comparable under enoxaparin and UFH treatment. PF 1 + 2 significantly decreased during both UFH (χ² ANOVA = 9.82, P = 0.007) and enoxaparin (χ² ANOVA = 29.40, P < 10^− 6) anticoagulated HD, while over-HD TAT levels changes differed depending on the type of heparin. The switch from enoxaparin to UFH treatment was connected with a significantly higher PF 1 + 2 after 10 and 180 min as well as higher TAT concentration after 180 min of HD. Only during enoxaparin anticoagulated HD 34% PF 1 + 2 decrease and TAT levels after 180 min of HD was closely associated with heparin dosage.

Conclusion

Single bolus of enoxaparin ensures efficient and convenient anti-thrombotic protection during HD procedure. Enoxaparin mean dose of 0.67 mg/kg, which is generally lower than manufacturer's instructions, can be recommended for over-dialytic regular use.     

Bilateral Orbital Haematomas in an Anticoagulated Patient with Severe H1N1 Influenza

A previously healthy woman was admitted to the intensive care unit (ICU) with severe H1N1 influenza. She had prolonged hospital stay due to multiple complications of critical illness, including pelvic deep vein thrombosis (DVT), which was treated with subcutaneous enoxaparin. The patient was referred to the ophthalmology service for bilateral proptosis. On examination, she had bilateral tense proptosis, worse on the left side with exposure keratopathy. Laboratory tests showed that she had thrombocytopenia and raised activated partial thromboplastin time (APTT). A CT scan revealed well-circumscribed soft tissue density lesions in the superolateral orbits and was reported as bilateral lacrimal gland enlargement. However, based on a clinical suspicion of subperiosteal hematoma collection, a diagnostic tap was performed. Following aspiration of six mls of dark blood from the left superior orbit, there was a reduction of proptosis with improvement in chemosis and resolution of exposure keratopathy. Enoxaparin is one of several antithrombotic agents which are increasingly being used for DVT prophylaxis in severely compromised patients. Furthermore, ICU patients ventilated for prolonged periods are at risk of developing chemosis and exposure keratopathy. Thus, the clinician should maintain a high index of suspicion in identifying subperiosteal hematomas, when managing such cases. The spontaneous bilateral vision threatening subperiosteal hematoma was probably caused by a combination of enoxaparin therapy and prolonged ventilation.     

改良皮下注射依诺肝素在老年冠心病患者介入治疗术后的应用

目的:探讨改良皮下注射依诺肝素在老年冠心病介入治疗术后的应用效果。方法:对82例患者腹部两侧用两种方法进行自身对照,右侧使用常规注射法注射依诺肝素,左侧使用改良皮下注射法注射依诺肝素,比较两种注射方法的注射部位出血发生率、出血程度、注射疼痛感、皮下硬结发生率。结果:与常规注射法比较,改良皮下注射法患者出血发生率低(P<0.01);出血和疼痛程度轻(P<0.01);皮下硬结发生率低(P<0.01)。结论:改良皮下注射法可明显减少注射部位皮下出血、皮下硬结形成及注射部位的疼痛程度,值得临床推广应用。     

Antifactor Xa Levels in Critically Ill Korean Patients Receiving Enoxaparin for Thromboprophylaxis: A Prospective Observational Study

The aim of this study was to investigate antifactor Xa (aFXa) levels after once daily dose of 40 mg of enoxaparin and to evaluate factors influencing aFXa levels among Korean intensive care unit (ICU) patients. This prospective observational study was conducted between August and December 2011 in medical ICUs at Samsung Medical Center. AFXa levels between 0.1 and 0.3 U/mL were considered to be effective for antithrombotic activity. Fifty-five patients were included. The median aFXa levels were 0.22 (IQR 0.17-0.26) at 4 hr, 0.06 (IQR 0.02-0.1) at 12 hr, and 0 U/mL (IQR 0-0.03) at 24 hr. The numbers of patients showing effective antithrombotic aFXa levels were 48 (87.3%), 18 (32.7%), and 0 (0%) at 4, 12 and 24 hr, respectively. At 12 hr, higher sequential organ failure assessment (SOFA) scores and hyperbilirubinemia were significantly associated with low aFXa levels (OR, 0.58; 95% CI, 0.36-0.93; P = 0.02 and 0.06; 0.003-0.87; 0.04, respectively). Once daily dose of 40 mg of enoxaparin is inadequate for maintaining effective antithrombotic aFXa levels, and the inadequacy is more salient for patients with high SOFA scores and hyperbilirubinemia.