American Society of Hematology 2019 guidelines for management of venous thromboembolism : prevention of venous thromboembolism in surgical hospitalized patients

Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). Conclusions: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.Peer reviewe

KNOWLEDGE, ATTITUDES AND PRACTICE OF VENOUS THROMBOEMBOLISM RISK ASSESSMENT AMONG SURGICAL DOCTORS IN TANZANIA

Introduction Surgical patients are at increased risk of venous thromboembolism due to the nature of their conditions and treatments. The incidence ranges from 61.3% to 64.9% in developed countries, compared to 43% in Africa. Although venous thromboembolism is fatal, it is potentially preventable. Physician-implemented risk assessment models reduce events by 70%. No country in sub-Sahara Africa has implemented a national venous thromboembolism risk assessment guideline. The subsequent burden is probably a reflection of low awareness and knowledge, negative attitudes, and substandard practice among physicians towards risk assessment. Justification In the current study, we assessed Tanzanian surgical doctors\u27 knowledge, attitudes, and practices of venous thromboembolism risk assessment and further determined whether surgical physicians\u27 age, gender, years of practice since graduation of bachelor of medicine (experience), and academic level were associated with their knowledge, attitudes, and practice on venous thromboembolism assessment. Findings of this study would allow conception of evidence-based recommendations and possible interventions targeted at reducing the incidence of hospital-acquired venous thromboembolism and its associated morbidity and mortality in Tanzania. Methods A prospective survey among surgical doctors was conducted at two, public national refferal level hospitals in Dar es salaam, Tanzania. A researcher-administered questionnaire was used. The questions on knowledge were adopted from PROMOTE study, and the questions on attitudes and practice domains were developed by the investigators. The knowledge and practice domains were assessed according to the 10th ACCP guidelines. Results: The overall mean venous thromboembolism knowledge score among surgical doctors was 55.2%. Although 66% of respondents felt hospitalization increased venous thromboembolism risk, 58% felt some surgical patients do not require venous thromboembolism risk assessment. About 45% felt venous thromboembolism prophylaxis increased treatment costs, 33% felt it increased hospital mortality and 47.7% felt some thromboprophylaxis interventions were ineffective. thromboembolism risk, only --- felt surgical patient required risk assessment. More than 8 out of 10 have had an experience of patient developing venous thromboembolism, a similar proportion doctors reported that they would prescribe thrombo-phylaxis in a patient with significant risk, however some setbacks like inadequate knowledge (53.8%) was reported to limit practice. Conclusion and Recommendations: The venous thromboembolism knowledge is not ideal among surgical doctors in Tanzanian refferal level hospitals, this adversely impacts attitudes and practice and is a patient safety risk. There is a need to develop and adopt a comprehensive hospital-wide policy on VTE and ensure implementation of its guidelines and protocols in all clinical settings. Knowledge gaps need to be addressed, and sustainable program for regular and frequent regular re-training of surgical doctors in Tanzania tertiary level hospitals on VTE, its risk assessment, prevention and management needs to be set up

Complications related to deep venous thrombosis prophylaxis in trauma: a systematic review of the literature

Deep venous thrombosis prophylaxis is essential to the appropriate management of multisystem trauma patients. Without thromboprophylaxis, the rate of venous thrombosis and subsequent pulmonary embolism is substantial. Three prophylactic modalities are common: pharmacologic anticoagulation, mechanical compression devices, and inferior vena cava filtration. A systematic review was completed using PRISMA guidelines to evaluate the potential complications of DVT prophylactic options. Level one evidence currently supports the use of low molecular weight heparins for thromboprophylaxis in the trauma patient. Unfortunately, multiple techniques are not infrequently required for complex multisystem trauma patients. Each modality has potential complications. The risks of heparin include bleeding and heparin induced thrombocytopenia. Mechanical compression devices can result in local soft tissue injury, bleeding and patient non-compliance. Inferior vena cava filters migrate, cause inferior vena cava occlusion, and penetrate the vessel wall. While the use of these techniques can be life saving, they must be appropriately utilized

Clinical Practice Guideline for Venous Thromboembolism

Background: The morbidity associated with venous thromboembolism often goes unrecognized. Identifying patient populations at risk for venous thromboembolism and implementing evidence-based guidelines can decrease the number of untoward effects of this disease. Clinical pathway guidelines are valuable tools needed by nurses in the prevention and treatment of disorders for patients. Education of the guideline can increase knowledge and understanding of what prevention, interventions, and treatment are available for the orthopaedic patient and how to apply this knowledge to everyday patient care.;Objective: To educate orthopaedic nurses on the clinical practice guidelines of thromboembolism.;Method: Incorporate the education of thromboembolism in an orthopaedic class intended for registered nurses studying for the national orthopaedic exam.;Population: Twenty-three registered nurses from the Mid-Ohio Valley employed at Selby General Hospital.;Expected Outcome: To calculate a statistically difference in the scores of a pre test and a post test given to the nurses enrolled in the class on the prevention and treatment of thromboembolism

Venous blood flow, thromboembolism and below knee cast immobilisation for trauma

Venous thromboembolism (VTE) has a background incidence of between 0.7 and 2.69 per 1000 per year (L. N. Roberts et al., 2013). Risk factors are either permanent or transient. Permanent risk factors include thrombophilia (80 x increase risk if homozygous for factor V Leiden), cancer (58 x increase risk if metastatic cancer or diagnosis within last 3 months), increasing age (risk doubles for each decade over age 40 years), family or personal history of deep vein thrombosis (2-3 x increase risk) and increasing body mass index (2 x increase for BMI > 35 kg/m2 in comparison with BMI <20 kgm2) (Y.-H. Kim & Kim, 2007) (Blom, Doggen, Osanto, & Rosendaal, 2005) (Anderson & Spencer, 2003) (Decramer, Lowyck, & Demuynck, 2008) (Holst, Jensen, & Prescott, 2010). Transient risk factors include surgery (165 x risk in first 6 weeks after total hip or knee replacement, equating to 2% symptomatic VTE rate) (Sweetland et al., 2009). Foot and ankle procedures including ankle fracture fixation, hindfoot fusion and 1st metatarsal osteotomy are associated with 18x, 8x and 2x increase VTE risk respectively (Jameson et al., 2011). Other transient risk factors include postpartum state (21-84 x increase in first 6 weeks), use of oral contraceptive pill or hormone replacement therapy (at least 2 x risk) and lower limb cast immobilization (Jackson, Curtis, & Gaffield, 2011) (Grodstein et al., 1996). Within 90 days of lower limb cast treatment, asymptomatic DVT affects between 4 and 40% of patients, symptomatic DVT affects 1 in 250, symptomatic pulmonary embolism affects 1 in 500, with fatal pulmonary embolism affecting 1 in 15,000 (Jameson et al., 2014). It is apparent that patients will therefore have a differing risks depending on their permanent and transient risks. The types of VTE include asymptomatic events, for which the relevance is not fully understood (often used in studies as a surrogate for symptomatic events). Symptomatic below knee DVT (approximately 20% propagate to become above knee) (Philbrick & Becker, 1988). Symptomatic above knee DVT (affecting popliteal vein or more proximal), which are 4 times more likely to occur (Baglin et al., 2010). Pulmonary embolism can also occur. The clinical relevance of DVT is that 6% of patients will have severe post thrombotic syndrome (venous ulceration, swelling, itching) at 10 years after the event, with 66% of patients displaying some signs (Schulman et al., 2006). Uncomplicated DVT does not appear to impact on quality of life, however if DVT is complicated by post thrombotic syndrome, patients will have significantly reduced quality of life, mental and physical health. Simple non fatal PE reduces physical health and if it is complicated by pulmonary hypertension (affecting approximately 2%) it results in significantly reduced quality of life, mental and physical health (Ghanima, Wik, Tavoly, Enden, & Jelsness-Jørgensen, 2017) (Lubberts, Paulino Pereira, Kabrhel, Kuter, & DiGiovanni, 2016). In view that VTE has significant effects on patients quality of life, it is important to try and prevent it. In order to develop strategies for preventing DVT in patients with lower limb injury treated with leg cast, it is important to investigate the relative contributions of injury, stasis and immobility to thrombogenesis. I start by performing systematic review of the literature to determine whether thromboprophylaxis reduces symptomatic venous thromboembolism in patients with below knee cast treatment for foot and ankle trauma. A systematic review of randomised controlled trials of thromboprophylaxis in patients with foot and ankle injuries treated with cast immobilization was performed, searching MEDLINE and EMBASE from inception to June 2015 (B. A. Hickey, Watson, et al., 2016b). Outcomes of interest were VTE (asymptomatic and symptomatic DVT and PE) and bleeding. 3 reviewers used a data extraction form and assessed the literature according to the Cochrane risk of bias tool. Statistical analysis was performed using RevMan. 7 studies of chemical thromboprophylaxis were included, all except one used venography to assess for DVT, with one study using venous ultrasound. 2 studies reported on mechanical thromboprophylaxis, neither reported symptomatic DVT events. Neither study of mechanical thromboprophylaxis found a reduction in asymptomatic DVT in the intervention group. Funnel plot of studies of chemical thromboprophylaxis suggested no publication bias. Pooled symptomatic DVT occurred in 1.58% of patients in the control group, with 0.43% sustaining symptomatic PE. At meta analysis, symptomatic DVT was reduced in the low molecular weight heparin chemical thromboprophylaxis group (OR 0.29, CI 0.09-0.95). Chemical thromboprophylaxis did not influence PE. There was one non-fatal retroperitoneal haemorrhage (major bleed), which equated to 0.11% (1 in 886). Based on these findings, 11 symptomatic VTE events would be prevented for every 1 major bleed. These findings are comparable with the recent Cochrane review, which included 2 additional studies and a total of 2924 participants. Meta analysis found reported a reduction of VTE in the LMWH chemical thromboprophylaxis group (OR 0.40, 95% CI 0.21-0.76) (Zee, van Lieshout, van der Heide, Janssen, & Janzing, 2017). In order to develop strategies for prediction and prevention of VTE in patients with foot and ankle injury treated with cast immobilization, it is necessary to consider why venous thrombosis occurs in these patients. As previously discussed, patients may have permanent risk factors, which may influence hypercoagulability. The transient risk factors of injury and cast treatment may also influence risk by causing endothelial dysfunction and venous stasis (Virchow, 1856). Several important mechanisms for prevention of venous stasis have previously been found. Weight bearing is important; with Gardner et al (1990) reporting that 30ml of venous contrast was pumped out of the foot during weight bearing (Gardner & Fox, 1983). This is not always possible for a patient with foot and ankle injury treated with a cast, because they may be non-weight bearing. For patients who are non-weight bearing, it is still possible to influence venous flow. For example, Elsner et al (2007) previously found that movement of the 1st metatarsophalangeal joint increased popliteal vein flow from 13 to 39 cm/s (Elsner, Schiffer, Jubel, Koebke, & Andermahr, 2007). In patients without leg casts, intermittent pneumatic compression of the leg or thigh to prevent venous stasis was found to be effective in reducing DVT and PE in a meta analysis of over 16, 000 patients (RR 0.43, 95% CI 0.36-0.52) (Ho & Tan, 2013). It therefore seems that this is a viable mechanism. Furthermore, Whitelaw et al (2001) found that none of the IPC devices studied resulted in significantly better calf pump function when compared with simple passive or active ankle movements (Whitelaw et al., 2001). To assess the influence of toe and ankle movement on venous stasis, I examine the effect of these movements on venous velocities measured at the popliteal vein with ultrasound. To determine whether this is a viable strategy for prevention of DVT, I then assess the impact of application of below knee cast on venous velocities. In this proof of principle study, 20 healthy volunteers were recruited (B. A. Hickey, Morgan, Pugh, & Perera, 2014). All had measurement of calf pump function in the un-casted leg whilst seated, using ultrasound at the popliteal vein. Baseline and peak velocities were measured during active toe movement (dorsiflexion and plantarflexion) and during ankle movement (dorsiflexion and plantarflexion). A below knee cast was then applied and measurements were repeated. Mean resting baseline venous velocity was 10 cm/s, which remained unchanged when the below knee cast was applied. There was approximately 5-fold increase in venous velocities with active toe movement (mean 54 cm/s for toe dorsiflexion, mean 50 cm/s for toe plantarflexion), and 10 fold increase from baseline with ankle movements (mean 115 cm/s ankle dorsiflexion, mean 87 cm/s ankle plantarflexion). All were statistically significant. When the below knee cast was applied, there was no statistically significant decrease in the peak velocities achieved during movement excepting for ankle dorsiflexion (isometric), however this was still increased approximately 8 times compared with baseline (88 cm/s). It was therefore apparent that venous stasis did not occur when a below knee cast was applied to healthy volunteers and that active toe movement may have a role in preventing stasis in patients with injury, with subsequent reduction in DVT. To determine whether this is true I assess the effect of active toe movement on calf pump function and asymptomatic deep vein thrombosis in patients with foot and ankle injury treated with leg cast. In this prospective randomized controlled trial, patients between the ages of 18 and 60 years with acute foot and ankle injury treated with non-weight bearing cast were recruited (B. A. Hickey, Cleves, et al., 2016a). Patients were within 3 days of their injury and considered low risk for VTE after risk assessment. Those with additional risk factors were provided with LMWH and not recruited. Patients who consented, were randomized to either active toe movement (AToM) intervention group (advised to perform active toe dorsiflexion and plantar flexion 60 times every 6 hours minimum, but more often if possible). Patients were managed through the trauma clinic according to their injury then had assessment of calf pump function on removal of cast and assessment for lower limb DVT of both lower limbs using venous ultrasound. Interim analysis was performed after the first 100 patients were recruited. 78 patients completed the study, mean age was 37 years, 65% were male. 59% had leg cast for ankle fracture. Analysis of calf pump function revealed no significant difference between the intervention and control groups for any of the parameters, with mean baseline popliteal velocity of 7 cm/s in both groups, popliteal venous velocity during active toe dorsiflexion 44 cm/s (AToM) v 34 cm/s (control), p=0.36 and popliteal venous velocity during active toe plantar flexion 39 cm/s (AToM) v 32 cm/s (control) p=0.35). 27% of patients were found to have asymptomatic DVT, with no significant difference between groups. The important finding was that all asymptomatic DVTs occurred in the lower limb that had been injured and treated with cast. This basic finding had not been previously reported in the literature. It was important to determine whether this finding could be attributable to venous stasis alone, or whether general immobility or the injury itself had any significant role. To answer this, I assess the association between patient mobility and development of asymptomatic DVT. As part of the AToM study, a triaxial accelerometer (MOVBand) was attached to the leg cast at time of recruitment to the study. This was removed in the trauma clinic at the first appointment and the first 5 days of accelerometer data was extracted. Unpaired t test was used to determine statistical significance between group means for patients who did and did not develop asymptomatic DVT. 78 patients completed the AToM study, 10 patients were excluded from accelerometer data analysis (4 trackers lost, 6 failed to record any data). There was no significant difference in accelerometer data between patients who did and did not sustain asymptomatic DVT. Average moves were 1057/day (no DVT group) vs 1005/day (DVT group), p=0.85. Average steps were 877/day (no DVT group) vs 825/day (DVT group), p=0.82. In view of this, it appeared that mobility of patients during the first week of cast treatment for injury did not predict subsequent finding of asymptomatic DVT. In view that all DVT’s occurred in the lower limb that had been injured and treated in cast, it was apparent that local factors such as venous stasis or tissue injury were more important than general patient mobility, otherwise it would be anticipated that some DVT’s would have occurred in the uninjured, un-casted limb. To investigate the role of the injury I examine the association between biomarkers of coagulation and tissue injury with the outcome of asymptomatic DVT. As part of the AToM study, 3.5ml venous blood was taken at time of recruitment. Centrifuged plasma was stored at -70 degrees centigrade. After the last patient exited the study, plasma was analysed for levels of tissue factor, interleukin 6, vascular cell adhesion molecule 1 (VCAM-1) and D-dimer (B. A. Hickey et al., 2017). 77 patients were included, 1 patient did not provide blood sample. Analysis of results found no difference between levels of tissue factor, IL-6, VCAM-1 and D-dimer in groups who did and did not sustain asymptomatic DVT. Mean Tissue factor 23.9 pg/mL (no DVT group) vs 20.3 (DVT group), p=0.422. Median IL-6 3.9 pg/mL (no DVT group) vs 4.6 (DVT group), p=0.76. Median VCAM-1 553 ng/mL (no DVT group) v 496.8 ng/mL (DVT group), p=0.11. Median D-dimer 203.5 (no DVT group) v 236.0 (DVT group), p=0.49. I therefore appeared that severity of injury, measured using plasma levels of FT, IL-6, VCAM-1 and D-dimer could not predict which patients would develop asymptomatic DVT. This suggested that local factors of venous stasis might play a greater role in thrombogenesis than tissue injury. In summary, it appears that chemical thromboprophylaxis reduces the risk of symptomatic DVT in patients with foot and ankle injury treated with leg casts. Active toe movements can prevent venous stasis in healthy volunteers, however this does not appear to influence calf pump function or occurrence of DVT in patients with injury and leg cast. The important finding from this work is that asymptomatic DVT only occurs in the lower limb that has been injured and treated with leg cast. Biomarkers of coagulation do no appear to predict DVT in this patient group. Similarly, general patient mobility measured objectively with accelerometer during the first week of cast treatment does not appear to be associated with development of DVT in patient with foot and ankle injury treated with leg casts

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation

Background Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. Objectives To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. Data sources Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. Review methods Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. Results Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84–89% and specificity of 46–55%. Limitations Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. Conclusions Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. Future work Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. Study registration This study is registered as PROSPERO CRD42017058688. Funding The National Institute for Health Research Health Technology Assessment programme