Perioperative Thromboprophylaxis Research Articles

Perioperative Thromboprophylaxis and Anticoagulation in Patients Undergoing Non-Cardiac Vascular Surgery

Patients undergoing non-cardiac vascular surgery (NCVS) are at high risk of developing perioperative venous and arterial thrombotic complications. Effective thromboprophylaxis is an essential part of the perioperative management of patients undergoing surgical procedures. To ensure appropriate delivery of antithrombotic agents and standardise clinical practice, numerous national and international guidelines have been developed in recent years. Very few of these recommendations are designed specifically for patients undergoing NCVS. This review aims to highlight the relevant guidelines and novel recommendations that are available for patients undergoing NCVS while noting their limitations and providing suggestions for specific subsets.

Novel Oral Anticoagulants

Patients undergoing surgery receive anticoagulation for perioperative thromboprophylaxis or ischemic cardiovascular disease. Because anticoagulants may also potentiate bleeding, clinicians need to understand the implications of anticoagulation in perioperative and postoperative patient management. Many newer anticoagulants that are now available or are in clinical development do not require routine coagulation monitoring, have more predictable dose responses, and have fewer interactions with other drugs and food. The most advanced oral anticoagulants in clinical development are the direct factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran etexilate. These agents have been evaluated in the postoperative setting in patients undergoing total hip- or knee-replacement surgery with promising results, and it remains to be seen whether these results will translate into other surgical settings. The impact of the new agents will be influenced by the balance between efficacy and safety, improved convenience, and potential cost-effectiveness benefits.

周術期静脈血栓塞栓症における薬物予防〜麻酔科医の立場から〜〈日本麻酔科学会周術期肺塞栓症調査結果より〉

周術期の静脈血栓塞栓症（VTE）に対する予防は普及しつつあるが，その次なるステップとして，薬物予防は重要な位置づけにある．日本麻酔科学会の調査報告から検討すると，抗凝固薬による予防は，周術期肺血栓塞栓症（PTE）死亡率を低下させる可能性が高い．一方で抗凝固薬使用時には，出血性合併症を十分に念頭におく必要があり，したがって硬膜外麻酔との併用における脊髄硬膜外血腫の問題も含め，管理プロトコールを設定する必要がある．

Prevention of venous thromboembolism after surgery

Most surgical patients who require hospitalization are at high risk for venous thromboembolism (VTE) and should receive VTE prophylaxis, usually including pharmacologic prophylaxis. Nevertheless, rates of appropriate perioperative thromboprophylaxis remain stubbornly low, though an expansion in quality-improvement efforts has led to widespread hospital implementation of prophylaxis strategies in recent years. This article reviews important principles and recent developments in perioperative VTE prophylaxis, with a focus on key recommendations and changes in the 2008 update of the American College Chest Physicians' (ACCP) evidence-based guidelines on antithrombotic therapy.

Prévention de la maladie thrombo-embolique veineuse péri-opératoire : que disent les 8 es recommandations de l’American College of Chest Physicians ?

Extensive evidence related to thromboembolism risk and its prevention are available to guide health care providers. The 8th ACCP Evidence-Based Clinical Practice Guidelines were published in June 2008. The chapter on venous thromboembolism prophylaxis is the result of the collaboration of six senior authors with expertise in thrombosis, surgery, medicine, and critical appraisal. The methodology and the philosophy of these guidelines are explained in this paper and the major recommendations dealing with perioperative thromboprophylaxis are summarized.

Venous thromboembolism in abdominal cancer surgery.

Venous thromboembolism (VTE) is recognized as a serious complication in both surgical and non-surgical patients. Cancer, particularly adenocarcinoma developing in the digestive organs, is one of the most potent risk factors for VTE, as first described by Trousseau in 1865. Cell membrane microparticles shedding from cancer cells play a critical role in venous clot formation through tissue factor (TF)-mediated activation of the coagulation system. Since recent prospective studies have demonstrated that VTE risk in Japanese surgical patients is comparable to that in Caucasians, perioperative thromboprophylaxis with anticoagulants is now considered essential in patients undergoing abdominal cancer surgery, in addition to mechanical thromboprophylaxis. Recent multi-center studies have also shown the efficacy and safety of enoxaparin, a low molecular weight heparin (LMWH), and fondaparinux, a synthetic Xa inhibitor, in VTE prevention after abdominal cancer surgery. Anticoagulants like LMWH are expected to exert not only thromboprophylactic but also antineoplastic effects.

Epidural bleeding after ACL reconstruction under regional anaesthesia: a case report

IntroductionEpidural bleeding as a complication of catheterization or epidural catheter removal is often associated with perioperative thromboprophylaxis especially in adult reconstructive surgery.Case presentationWe report on a case of a 19 years old male athlete that underwent anterior cruciate ligament reconstruction, receiving low molecular weight heparin for thromboprophylaxis and developed an epidural hematoma and subsequent cauda equina syndrome two days after removal of the epidural catheter. An urgent magnetic resonance imaging scan revealed an epidural hematoma from the level of L3 to L4. Emergent decompression and hematoma evacuation resulted in patient's significant neurological improvement immediately postoperatively.ConclusionA high index of clinical suspicion and surgical intervention are necessary to prevent such potentially disabling complications especially after procedures on a day-case basis and early patient's discharge.

Minimizing tumor burden by extensive cytoreductive surgery decreases postoperative venous thromboembolism in ovarian clear cell carcinoma

A venous thromboembolism (VTE) is prevalent in patients with ovarian clear cell carcinoma (OCCC). Tumor burden and extensive cytoreductive surgery are well-known risk factor for a VTE. The purpose of this study was to define the incidence of VTE after extensive cytoreductive surgery and to clarify the relationship between VTE and extensive cytoreductive surgery in patients with OCCC. We reviewed the medical charts of 43 patients treated at the National Cancer Center between June 2000 and July 2007. Most surgical procedures were performed with peri-operative thrmoboprophylaxis. Eight (18.6%) patients had deep vein thromboses and three of eight patients had a pulmonary thromboembolism. A VTE was identified at initial presentation in four patients, at recurrence in one patient, and during 3rd line chemotherapy in three patients when the patients had a bulky tumor burden. The rate of optimal debulking surgery was 95.3% and no patient had a VTE during the postoperative recovery period and adjuvant chemotherapy. A VTE was associated with disease status only (P=0.042). Minimizing residual tumor by extensive cytoreductive surgery with peri-operative thromboprophylaxis may decrease the incidence of a postoperative VTE in patients with OCCC. Larger, prospective studies are needed to confirm these preliminary findings.

Risk-Group Targeted Inferior Vena Cava Filter Placement in Gastric Bypass Patients

Despite a growing body of evidence guiding appropriate perioperative thromboprophylaxis in the general population, few data direct strategies to reduce deep venous thrombosis (DVT) and pulmonary embolism (PE) in the morbidly obese. We have implemented a novel protocol for venous thromboembolism (VTE) risk stratification in Roux-en-Y gastric bypass (RYGB) candidates at our institution, which augments clinical assessment with screening for thrombophilias, to guide retrievable inferior vena cava (IVC) filter utilization. A retrospective review of prospectively collected data from patients who underwent primary RYGB between 2001 and 2008 at the University of North Carolina at Chapel Hill was completed. During that time, clinical assessment of VTE risk was amplified by focused plasma screening for common thrombophilias (factors VIII, IX, and XI, d-dimer, fibrinogen). Preoperative prophylactic IVC filters were offered to high-risk patients. The database was reviewed for perioperative DVTs, PEs, and filter-related complications. Of 330 patients, in 162 attempts, 160 had prophylactic IVC filters placed with four complications overall (2.47%). No patient had symptoms of PE during the planned 6-week filter period, though one had a PE occur immediately after filter removal (0.63%); in contrast, five of 170 patients (2.94%) without prophylactic IVC filters presented with symptomatic PE (p = 0.216). In total, 147 (91.88%) prophylactic filters were removed. Risk-group targeted prophylactic inferior vena cava filter placement prior to RYGB is safe with a trend towards reduced occurrence of PE.

Review: Perioperative LMW heparin does not reduce mortality after surgery more than unfractionated heparin in patients with cancer

Source Citation Akl EA, Terrenato I, Barba M, et al. Low-molecular-weight heparin vs unfractionated heparin for perioperative thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Arch Intern Med. 2008;168:1261-9. 18574082

Low-Molecular-Weight Heparin vs Unfractionated Heparin for Perioperative Thromboprophylaxis in Patients With Cancer<subtitle>A Systematic Review and Meta-analysis</subtitle>

The relative benefits and harms of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) are required for judgments regarding the appropriate perioperative thromboprophylaxis in patients with cancer. We systematically reviewed the literature to quantify these effects. The comprehensive searches included (1) an electronic search of MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL (The Cochrane Central Register of Controlled Trials); (2) a hand search of relevant conference proceedings; (3) a reference check of included trials; and (4) use of the PubMed "Related Articles" feature. Outcomes of interest included mortality, deep venous thrombosis, pulmonary embolism, bleeding complications, and thrombocytopenia. Of 3986 identified citations, we included 14 randomized clinical trials in the meta-analysis (all using preoperative prophylactic anticoagulation). The overall methodological quality was moderate. The meta-analysis showed no differences in mortality in patients receiving LMWH compared with UFH (relative risk [RR], 0.89; 95% confidence interval [CI], 0.61-1.28) or in clinically suspected deep venous thrombosis (RR, 0.73; 95% CI, 0.23-2.28). In a post hoc analysis including all studies assessing deep venous thrombosis, irrespective of the diagnostic strategy used, LMWH was superior to UFH (RR, 0.72; 95% CI, 0.55-0.94). There were no differences in rates of pulmonary embolism (RR, 0.60; 95% CI, 0.22-1.64), minor bleeding (RR, 0.88; 95% CI, 0.47-1.66), or major bleeding (RR, 0.95; 95% CI, 0.51-1.77). We found no differences in mortality in patients with cancer receiving perioperative thromboprophylaxis with LMWH vs UFH. Further trials are needed to more carefully evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population.

Perioperative thromboprophylaxis in children: development of a guideline for management

Venous thromboembolic (VTE) events can occur in children at the time of surgery where a patient has associated prothrombotic risk factors. There is currently little advice available to anesthetists on how to assess the risks and provide prophylaxis. To increase awareness of thrombosis in the perioperative pediatric patient, and to give some guidance when considering prophylaxis in this group. A guideline outlining risk factors for venous thromboembolism in patients presenting for surgery was written as a flowchart. Recommendations for low risk patients was early mobilization and good hydration; for moderate risk patients having major general surgery to include physical prophylaxis where size permits, i.e. elastic stockings and compression devices; for high-risk patients undergoing major orthopaedic or general surgery to also receive prophylactic low molecular weight heparin enoxaparin 0.5 mg x kg(-1) b.d. Children with multiple risk factors for VTE should be considered for prophylactic measures when presenting for prolonged major surgery.

Anticoagulation in patients with cancer: an overview of reviews

Relative benefits and harms of anticoagulants are required for judgments regarding appropriate anticoagulation in patients with cancer. To review the benefits and harms of anticoagulants for prophylactic, therapeutic, and survival improvement indications in patients with cancer. Overview of 6 systematic reviews of anticoagulation in cancer following the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation methodology. Central venous catheters thromboprophylaxis with heparin or warfarin does not significantly reduce the incidence of symptomatic deep vein thrombosis (DVT) (relative risk [RR] 0.43, 95% CI 0.18-1.06 and RR 0.62, 95% CI 0.30-1.27 respectively). For perioperative thromboprophylaxis, low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have similar effects on mortality (RR 0.89, 95% CI 0.61-1.28) and morbidity outcomes. For the initial treatment of venous thromboembolism (VTE), LMWH compared with UFH reduces mortality at 3 months (RR 0.71, 95% CI 0.52-0.98). For the long-term treatment of VTE, LMWH compared with vitamin K antagonists reduces VTE recurrence (hazard ratio [HR] 0.47, 95% CI 0.32-0.71) but not mortality (HR 0.96, 95% CI 0.81-1.14). As interventions to improve survival, warfarin suggests a survival benefit at 6 months in the subgroup of small cell lung cancer (SCLC) (RR 0.69, 95% CI 0.50-0.96) while heparin suggests a survival benefit in patients with cancer in general (HR 0.77, 95% CI 0.65-0.91) and in those with limited SCLC in particular (HR 0.56, 95% CI 0.38-0.83). In patients with cancer, current evidence does not support routine use of thromboprophylaxis for central venous catheters or a specific anticoagulant for perioperative thromboprophylaxis. Anticoagulants may improve survival, but more data will be useful in deciding which subgroups benefit most.

Extended perioperative thromboprophylaxis in patients with cancer

We systematically reviewed the literature to compare the relative efficacy and safety of extended versus limited duration heparin for perioperative thromboprophylaxis in patients with cancer. We followed the Cochrane Collaboration systematic review methodology and searched MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL. The outcomes of interest included mortality, symptomatic deep venous thrombosis (DVT), pulmonary embolism, and bleeding. We evaluated the quality of evidence by outcome using the GRADE approach. Of 3,986 identified citations, we included three randomized clinical trials using low-molecular-weight heparin (LMWH). The quality of evidence for mortality, DVT, and major bleeding was low. There was no significant difference between extended (4 weeks) and limited duration thromboprophylaxis in terms of death at three months (relative risk [RR] = 0.49; 95% confidence interval [CI] 0.12-1.94), or major bleeding at four weeks (RR = 2.94; 95% CI 0.12-71.85). An extended regimen was associated with a significantly lower risk of asymptomatic DVT (RR = 0.21; 95% CI 0.05-0.94). No data was available for symptomatic DVT. In conclusion, there is limited and low-quality evidence that extended duration LMWH for perioperative thromboprophylaxis reduces DVT in patients with cancer undergoing major abdominal or pelvic surgery. More and better quality evidence is needed to justify extended regimens.

Technical Considerations in the Operative Management of Femoral Neck Fractures in Elderly Patients: A Multinational Survey

To identify current opinions among orthopedic traumatologists relating to technical aspects of internal fixation and arthroplasty for patients with femoral neck fractures. We developed and administered a survey to orthopedic surgeons who were members of the Orthopedic Trauma Association and European clinics affiliated with AO International (Davos, Switzerland). Surgeons reported preferences in specific aspects of the surgical technique for internal fixation as well as arthroplasty. Each surgeon received either a mailed package (7-page survey, a personalized cover letter, and a stamped return envelope) or an email with a link to the same survey on the Internet with an identification code. At 6 weeks, 12 weeks, and 18 weeks after the initial mailing, we remailed the questionnaire to all nonresponders. Of the 442 surgeons who were sent the questionnaire, 298 (68%) responded. The typical respondent was a North American aged more than 40 years, in academic practice, supervised residents, had fellowship training in trauma, and worked in a low-volume center. Among surgeons who treated displaced femoral neck fractures with arthroplasty, significant disparities existed in terms of the type of anesthesia (51% preferring general anesthesia), surgical approach (47% used posterior approach), and placement of unipolar implants (50%). Surgeons tended to agree on the use of cement fixation (69%), repairing the capsule (80%), and not using a drain postoperatively (68%). Surgeons who preferentially treated hip fractures with internal fixation tended to have a lack of consensus in terms of what constituted acceptable surgical delays (43% allowing greater than 48 hours) and which screw configuration to use, with more than half using a triangle with base inferior construct. Surgeons tended to agree on the use of closed fracture reduction techniques (69%), three cannulated screws (73%), and did not routinely perform a capsulotomy (80%) or aspirate the fracture hematoma (90%). Within both treatment groups (internal fixation and arthroplasty), surgeons tended to agree on the use of perioperative antibiotics (>92%), thromboprophylaxis (98%), and postoperative weight bearing status (>87%). A general lack of consensus exists among orthopedic trauma surgeons in the management of displaced femoral neck fractures. With an ever-growing emphasis upon the practice of evidence-based medicine, we have demonstrated several disparities in the technical aspects of fixation and perioperative care likely caused by a general lack of available evidence. We recommend the need for future research and large collaborative efforts.

Anesthesia and Orthopaedic Surgery.

Anesthesia and Orthopaedic Surgery.

Delayed Subarachnoid Hematoma After Continuous Epidural Anesthesia in a Patient Without Risk Factors: Good Outcome After Late Laminectomy

To the Editor: Subarachnoid hematoma is a rare but serious neurological complication of neuraxial anesthesia, with an incidence of approximately 1:150,000 after epidural blockade (1,2). Thirty percent of patients with spinal subarachnoid hematoma have no risk factors. The incidence in these patients is 1:200,000 after epidural blockade (3). Patients with acute spinal subarachnoid hematoma should undergo laminectomy and decompression within 8 h (1) to minimize neurological injury. We report a case of an ASA I 50-yr-old man, without risk factors for increased bleeding or perioperative thromboprophylaxis, who underwent left herniorrhaphy under epidural anesthesia. His routine preoperative coagulation tests included prothrombin time, activated partial thromboplastin time, and international normalized ratio. The epidural was easily placed in a single attempt at the L3–L4 interspace. The epidural catheter was threaded 4 cm cephalad. No adverse events occurred during the 45 min of surgery. The epidural catheter was removed at the end of the surgery. On the third day after surgery, the patient developed bilateral lumbar pain and paresthesias in the lower limbs. Thinking he had acute sciatica, we treated him with 100 mg a day of ketoprofen, and his symptoms partially improved. Four days later his symptoms returned, accompanied by complete paralysis of the lower limbs. A magnetic resonance imaging (MRI) scan revealed an extensive L2–L4 subarachnoid hematoma (Fig. 1). The patient underwent an emergency laminectomy. Over the next 2 days, the patient’s neurological symptoms resolved slowly. He was discharged 5 days after surgery, with full neurological recovery.Figure 1.: L2–L4 subarachnoid hematoma after epidural puncture.Diagnosis of spinal hematoma was complicated by a lack of risk factors and the late onset of symptoms. The symptoms of acute neuroaxial hematoma often occur within the first 24 h, although onset may vary between 15 min and 7 days. The differential diagnosis of a radicular pain after neuraxial anesthesia includes several clinical syndromes (1,4,5). However, there was no clinical evidence to suggest epidural abscess, bacterial or aseptic meningitis, anterior spinal artery syndrome, traumatic cord lesions, or transitory radicular syndrome (4). The diagnosis of hematoma was made clinically, and confirmed by MRI scan. The usual recommendation is laminectomy within 8 h of onset (2), although there are cases with complete recovery when surgery took place 72 h after the onset of symptoms (6). In our case, the patient had a good outcome, despite the delayed diagnosis and therapy. Esther Agustín, MD Cesar Aldecoa, MD Jesús Rico-Feijoo, MD Jose Ignacio Gómez-Herreras, MD, PhD Department of Anesthesiology and Postoperative Critical Care Rio Hortega University Hospital Valladolid, Spain [email protected]

Cost-effectiveness of Thromboprophylaxis With Intermittent Pneumatic Compression at Cesarean Delivery

To evaluate the cost-effectiveness of thromboprophylaxis at cesarean delivery with intermittent pneumatic compression. A decision tree model using Markov analysis was developed to compare two approaches to perioperative care at the time of cesarean delivery: 1) no use of perioperative thromboprophylaxis and 2) the use of intermittent pneumatic compression for thromboprophylaxis at the time of cesarean delivery. Postcesarean deep venous thrombosis was estimated to occur in 0.7% of patients (75% of whom were asymptomatic), and result in a 9% chance of postthrombotic syndrome. Mechanical prophylaxis was assumed to decrease the risk of deep venous thrombosis by 70% and to cost 120 dollars. Probability of morbidity and mortality of venous thromboembolism as well as anticoagulation and the costs and utilities for different health state were derived from published studies. Sensitivity analysis was performed over a wide range of variable estimates. Using the assumptions in our base case, routine thromboprophylaxis for cesarean delivery cost 39,545 dollars per quality-adjusted life year. One-way sensitivity analysis revealed that as long as the incidence of postcesarean deep venous thrombosis was at least 0.68%, intermittent pneumatic compression reduced the incidence of deep venous thrombosis by at least 50%, or the cost of intermittent pneumatic compression was less than 180 dollars, the cost-effectiveness of mechanical prophylaxis did not exceed 50,000 dollars per quality-adjusted life year. Mechanical thromboprophylaxis is estimated to be a cost-effective strategy under a wide range of circumstances.

Enoxaparin for Thromboprophylaxis in Morbidly Obese Patients Undergoing Bariatric Surgery: Findings of the Prophylaxis Against VTE Outcomes in Bariatric Surgery Patients Receiving Enoxaparin (PROBE) Study

Obese patients undergoing bariatric surgery are at significant risk for venous thromboembolism (VTE). We performed a multicenter, retrospective survey to evaluate the safety and efficacy of enoxaparin for thromboprophylaxis in patients with morbid obesity undergoing primary bariatric surgery. From January to December 2002, 668 patients who underwent primary bariatric surgery at 5 centers were analyzed retrospectively. Baseline patient demographics, objectively diagnosed cases of VTE, and bleeding events were recorded. Patients received enoxaparin preoperatively (30 mg) or postoperatively (40 mg) every 12 or 24 hours or upon discharge (30 mg every 24 hours for 10 days). Overall, there were 6 (0.9%) pulmonary embolisms (PE) and 1 (0.1%) occurrence of deep vein thrombosis (DVT); all but 1 occurred after the cessation of thromboprophylaxis. The highest incidence of VTE was at Center B, which did not administer perioperative thromboprophylaxis (1 DVT and 2 PEs). There were 6 (0.9%) severe bleeding complications: 3 at center D and 3 at center E. In Center B, 2 deaths were recorded (0.3%): 1 due to sepsis and 1 due to bleeding, with both occurring after thromboprophylaxis was discontinued. The administration of enoxaparin, in various dosing regimens, is safe for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery. Fewer events occurred with perioperative prophylaxis initiated in the hospital. Because all thromboembolic events occurred after the cessation of thromboprophylaxis, extended thromboprophylaxis may be of value.

Compliance of dutch orthopedic departments with national guidelines on thromboprophylaxis

All 110 Dutch orthopedic departments were sent a survey on perioperative thromboprophylaxis protocols, and 79% responded. After hip and knee replacements, all used pharmacological thromboprophylaxis: a low-molecular weight heparin (LMWH) in 87% of departments, which was most often combined with vitamin K antagonists (VKAs). LMWH was usually started preoperatively (91%). After discharge, VKAs were mostly prescribed (79%) for at least 6 weeks, and often for 3 months. 17% of departments used LMWH for 6 weeks, whereas in only 3% no post-discharge prophylaxis was given.In day-care surgery, including arthroscopies, 58% use LMWH and in short-stay surgery 80% administer LMWH during the hospital stay. Because of lack of conclusive evidence for day-care surgery, the national guidelines cannot support pharmacological prophylaxis in this setting.In general, Dutch orthopedic departments comply poorly with the national guidelines on extended thromboprophylaxis for hip and knee replacement surgery, which recommends postoperative LMWH for 6 weeks. They are divided in the use of pharmacological prophylaxis in day-care surgery.