The Thresholds of Caprini Score Associated With Increased Risk of Venous Thromboembolism Across Different Specialties: A Systematic Review.

OBJECTIVE: Estimation of the specific thresholds of the Caprini risk score (CRS) that are associated with the increased incidence of venous thromboembolism (VTE) across different specialties, including identifying the highest level of risk. BACKGROUND: Accurate risk assessment remains an important but often challenging aspect of VTE prophylaxis. One well-established risk assessment model is CRS, which has been validated in thousands of patients from many different medical and surgical specialties. METHODS: A search of MEDLINE and the Cochrane Library was performed in March 2022. Manuscripts that reported on (1) patients admitted to medical or surgical departments and (2) had their VTE risk assessed by CRS and (3) reported on the correlation between the score and VTE incidence, were included in the analysis. RESULTS: A total of 4562 references were identified, and the full text of 202 papers was assessed for eligibility. The correlation between CRS and VTE incidence was reported in 68 studies that enrolled 4,207,895 patients. In all specialties, a significant increase in VTE incidence was observed in patients with a CRS of ≥5. In most specialties thresholds of ≥7, ≥9, and ≥11 to 12 were associated with dramatically increased incidences of VTE. In COVID-19, cancer, trauma, vascular, general, head and neck, and thoracic surgery patients with ≥9 and ≥11 to 12 scores the VTE incidence was extremely high (ranging from 13% to 47%). CONCLUSION: The Caprini score is being used increasingly to predict VTE in many medical and surgical specialties. In most cases, the VTE risk for individual patients increases dramatically at a threshold CRS of 7 to 11.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism.

BACKGROUND: It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is the second update of the review first published in 2008. OBJECTIVES: The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis compared to single modalities in preventing VTE. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 18 January 2021. We searched the reference lists of relevant articles for additional studies.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE compared to either intervention individually. DATA COLLECTION AND ANALYSIS: We independently selected studies, applied Cochrane's risk of bias tool, and extracted data. We resolved disagreements by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were PE, DVT, bleeding and major bleeding. MAIN RESULTS: We included a total of 34 studies involving 14,931 participants, mainly undergoing surgery or admitted with trauma. Twenty-five studies were RCTs (12,672 participants) and nine were CCTs (2259 participants). Overall, the risk of bias was mostly unclear or high. We used GRADE to assess the certainty of the evidence and this was downgraded due to the risk of bias, imprecision or indirectness. The addition of pharmacological prophylaxis to IPC compared with IPC alone reduced the incidence of symptomatic PE from 1.34% (34/2530) in the IPC group to 0.65% (19/2932) in the combined group (OR 0.51, 95% CI 0.29 to 0.91; 19 studies, 5462 participants, low-certainty evidence). The incidence of DVT was 3.81% in the IPC group and 2.03% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.51, 95% CI 0.36 to 0.72; 18 studies, 5394 participants, low-certainty evidence). The addition of pharmacological prophylaxis to IPC, however, increased the risk of any bleeding compared to IPC alone: 0.95% (22/2304) in the IPC group and 5.88% (137/2330) in the combined group (OR 6.02, 95% CI 3.88 to 9.35; 13 studies, 4634 participants, very low-certainty evidence). Major bleeding followed a similar pattern: 0.34% (7/2054) in the IPC group compared to 2.21% (46/2079) in the combined group (OR 5.77, 95% CI 2.81 to 11.83; 12 studies, 4133 participants, very low-certainty evidence). Tests for subgroup differences between orthopaedic and non-orthopaedic surgery participants were not possible for PE incidence as no PE events were reported in the orthopaedic subgroup. No difference was detected between orthopaedic and non-orthopaedic surgery participants for DVT incidence (test for subgroup difference P = 0.19).  The use of combined IPC and pharmacological prophylaxis modalities compared with pharmacological prophylaxis alone reduced the incidence of PE from 1.84% (61/3318) in the pharmacological prophylaxis group to 0.91% (31/3419) in the combined group (OR 0.46, 95% CI 0.30 to 0.71; 15 studies, 6737 participants, low-certainty evidence). The incidence of DVT was 9.28% (288/3105) in the pharmacological prophylaxis group and 5.48% (167/3046) in the combined group (OR 0.38, 95% CI 0.21 to 0.70; 17 studies; 6151 participants, high-certainty evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (any bleeding: OR 0.87, 95% CI 0.56 to 1.35, 6 studies, 1314 participants, very low-certainty evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, 5 studies, 908 participants, very low-certainty evidence). No difference was detected between the orthopaedic and non-orthopaedic surgery participants for PE incidence (test for subgroup difference P = 0.82) or for DVT incidence (test for subgroup difference P = 0.69). AUTHORS' CONCLUSIONS: Evidence suggests that combining IPC with pharmacological prophylaxis, compared to IPC alone reduces the incidence of both PE and DVT (low-certainty evidence). Combining IPC with pharmacological prophylaxis, compared to pharmacological prophylaxis alone, reduces the incidence of both PE (low-certainty evidence) and DVT (high-certainty evidence). We downgraded due to risk of bias in study methodology and imprecision. Very low-certainty evidence suggests that the addition of pharmacological prophylaxis to IPC increased the risk of bleeding compared to IPC alone, a side effect not observed when IPC is added to pharmacological prophylaxis (very low-certainty evidence), as expected for a physical method of thromboprophylaxis. The certainty of the evidence for bleeding was downgraded to very low due to risk of bias in study methodology, imprecision and indirectness. The results of this update agree with current guideline recommendations, which support the use of combined modalities in hospitalised people (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed to provide evidence for specific patient groups and to increase our certainty in the evidence.

Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation.

BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).

Development of a Novel Composite Process Measure for Venous Thromboembolism Prophylaxis.

BACKGROUND: Postoperative venous thromboembolism (VTE) is important clinically, and VTE quality metrics are used in public reporting and pay-for-performance programs. However, current VTE outcome measures are not valid due to surveillance bias, and the Surgical Care Improvement Project (SCIP-VTE-2) process measure only requires prophylaxis within 24 hours of surgery. OBJECTIVES: We sought to (1) develop a novel measure of VTE prophylaxis that requires early ambulation, mechanical prophylaxis, and chemoprophylaxis throughout the hospitalization, and (2) compare hospital performance on the SCIP-VTE-2 process measure to this novel measure. RESEARCH DESIGN: A new composite measure of ambulation, sequential compression device (SCD), and chemoprophylaxis component measures was developed. The ambulation component required daily ambulation, the SCD component required documentation of continuous use, and the chemoprophylaxis component required patient-appropriate and medication-appropriate dosing and administration. Requirements could also be met with component-specific exceptions. Surgical patients at an academic center from 2012 to 2013 were assessed for SCIP-VTE-2 and composite measure adherence. RESULTS: Of 786 patients, 589 (74.9%) passed the ambulation measure, 494 (62.8%) passed the SCD measure, and 678 (86.3%) passed the chemoprophylaxis measure. A total of 268 (91.8%) SCD failures and 46 (42.6%) chemoprophylaxis failures were ordered but not administered. When comparing the 2 measures, 784 (99.7%) passed SCIP-VTE-2, whereas only 364 (46.3%) passed the composite measure (P<0.001). CONCLUSIONS: This new measure incorporates the critical aspects of VTE prevention to ensure defect-free care. After additional evaluation, this composite VTE prophylaxis measure with appropriate exclusion criteria may be a better alternative to existing VTE process and outcome measures.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism.

BACKGROUND: It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is an update of the review first published in 2008. OBJECTIVES: The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis versus single modalities in preventing venous thromboembolism. SEARCH METHODS: For this update the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (May 2016). In addition the CIS searched the Cochrane Register of Studies (CENTRAL (2016, Issue 4)). Clinical trials databases were searched for details of ongoing or unpublished studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE. DATA COLLECTION AND ANALYSIS: We independently selected trials and extracted data. Disagreements were resolved by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. MAIN RESULTS: We included a total of 22 trials (9137 participants) of which 15 were randomized trials (7762 participants). The overall risk of bias was mostly unclear or high due to selection and performance bias. We used GRADE to assess the quality of the evidence and this was downgraded from high to moderate or very low due to the risk of bias, imprecision or indirectness.The rate of PE in the studies comparing IPC alone with combined IPC and pharmacological prophylaxis was low, underpowering the analyses. The incidence of symptomatic PE was 0.79% with IPC, but ranged between 0.1 to 1% with combined IPC and pharmacological prophylaxis (OR 0.49, 95% CI 0.18 to 1.34; 12 studies, 3017 participants, moderate quality evidence). The incidence of DVT was 4.10% in the IPC group and 2.19% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.52, 95% CI 0.33 to 0.82; 11 studies, 2934 participants, moderate quality evidence). The addition of an anticoagulant to IPC, however, increased the risk of any bleeding compared to IPC alone; 0.66% (7/1053) in the IPC group and 4.0% (44/1102) in the combined group (OR 5.04, 95% CI 2.36 to 10.77; 7 studies, 2155 participants, moderate quality evidence). Major bleeding followed a similar pattern; 0.1% (1/1053) in the IPC group to 1.5% (17/1102) in the combined group (OR 6.81, 95% CI 1.99 to 23.28; 7 studies, 2155 participants, moderate quality evidence).We detected no difference between the type of surgery subgroups such as orthopedic and non-orthopedic participants for DVT incidence (P = 0.16). Tests for differences between type of surgery subgroups were not possible for PE incidence.Compared with pharmacological prophylaxis alone, the use of combined IPC and pharmacological prophylaxis modalities reduced the incidence of symptomatic PE from 2.92% to 1.20% (OR 0.39, 95% CI 0.23 to 0.64; 10 studies, 3544 participants, moderate quality evidence). The incidence of DVT was 6.2% in the pharmacological prophylaxis group and 2.9% in the combined group showing no difference between the combined and pharmacological prophylaxis groups (OR 0.42, 95% CI 0.18 to 1.03; 11 studies, 2866 participants, moderate quality evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (bleeding: OR 0.80, 95% CI 0.30 to 2.14, very low quality evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, very low quality evidence, 3 studies, 244 participants).No difference was detected between the type of surgery subgroups for PE incidence (P = 0.68) or for DVT incidence (P = 0.10). AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that combining IPC and pharmacological prophylaxis, compared with IPC or pharmacological prophylaxis alone, decreases the incidence of DVT when compared to compression, and incidence of PE when compared to anticoagulation. Moderate quality evidence suggests that there is no difference between combined and single modalities in the incidence of PE when compared with compression alone and DVT when compared with anticoagulation alone. The quality of evidence for PE or DVT was downgraded to moderate due to imprecision or risk of bias in study methodology, highlighting the need for further research. Moderate quality evidence suggests the addition of pharmacological prophylaxis to IPC, increased the risk of bleeding compared to IPC alone, a side effect not observed for IPC when added to pharmacological prophylaxis (very low quality evidence), as expected for a physical method of thromboprophylaxis. The quality of evidence for bleeding was downgraded to moderate due to indirectness or very low due to risk of bias in study methodology, indirectness and imprecision highlighting the need for further research. Nevertheless, the results of the current review agree with current guideline recommendations, which support the use of combined modalities in hospitalised patients (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed.

Adaptive compression therapy for venous leg ulcers: a clinically effective, patient-centred approach.

A prospective, randomised, 12-week study was performed to evaluate the efficacy and tolerability of two compression methods for venous leg ulcers (VLUs); a new adaptive compression therapy (ACT) system, combining intermittent and sustained pneumatic compression (n = 38) and a conventional four-layer bandage system (n = 52). Primary outcomes were ulcer healing and safety. Secondary outcomes were comfort, compliance, ulcer pain, patient-perceived product performance and quality of life. Ulcer healing rate was similar (31·6% versus 42·3%, respectively, P = 0·30) between the treatments. Adverse events and patient-rated comfort were also similar. Average daily usage for the dual system was 10·5 and 1·8 hours in the sustained and intermittent modes, respectively, representing its use during 71% of waking hours. Predicted final ulcer pain was also similar (P = 0·68). Performance was subjectively better for adaptive compression and significantly higher for exudate management (P = 0·04), skin protection (P < 0·001), removal ease (P = 0·0007), bathing (P < 0·0001) and sleep comfort (P = 0·0405). The adjusted final quality-of-life score was 0·1025 higher for adaptive compression (P = 0·0375). Subjects with healed ulcers attained higher final scores than unhealed subjects (P = 0·0004). This study provides evidence that ACT is comparably efficacious to successfully heal VLUs compared with four-layer bandage management but is better accepted and achieves higher patient-reported quality-of-life scores in these challenging patients.

Dissecting the rationale for thromboprophylaxis in challenging surgical cases.

Pulmonary embolism (PE) is a leading preventable cause of death in surgical patients, and rates of fatal PE are increasing. Individual assessment, to balance the risks of thrombosis and bleeding, is the key to providing appropriate prophylaxis. The risk assessment process includes use of evidence-based guidelines, literature published since the latest guidelines, large registries, and risk scoring systems together with clinical experience and judgment. Risk assessment is a dynamic process and needs to be updated both during the hospital stay and just prior to discharge since clinical events may change the level of risk. The final assessment may identify patients who require ongoing anticoagulant prophylaxis after discharge. The Caprini risk score is widely used in surgical patients and is a composite of the number of risk factors and their relative weights. The Caprini risk score set point for risk levels requiring anticoagulant prophylaxis varies depending on the type of surgical procedure, surgical population, and number of risk factors. Mandatory implementation of evidence-based care pathways is helpful in lowering PE-related mortality. This review presents several challenging cases, emphasizing the importance of employing all available assessment tools, including dynamic assessment of risk during hospitalization. Finally, the limitations of evidence-based guidelines in complex scenarios and the need to employ all available tools to properly protect very high-risk patients are emphasized.

Current state of knowledge on oral anticoagulant reversal using procoagulant factors.

OBJECTIVE: To discuss current trends and challenges in the use of procoagulants for treating bleeding caused by use of oral anticoagulants. DATA SOURCES: Literature searches of PubMed (MEDLINE), Google, and Medscape were conducted in February 2013. There were no date limitations. Search terms included anticoagulation agents, anticoagulation reversal, anticoagulation reversal agents, apixaban, clinical studies, dabigatran, 3-factor PCCs, 4-factor PCCs, FEIBA, fresh frozen plasma, human studies, pharmacology, prescribing information, rFVIIa, rivaroxaban, vitamin K, and warfarin. DATA SYNTHESIS: Warfarin has been the mainstay for the treatment and prevention of primary and secondary thrombosis in patients with cardiovascular dis orders such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and stroke. Three oral anticoagulants have recently become available in the US: a direct thrombin inhibitor, dabigatran etexilate, and 2 direct factor Xa inhibitors, rivaroxaban and apixaban. Reversal strategies for anticoagulant-associated bleeding are well established for warfarin; however, strategies to stop bleeding in a patient who has taken one of the newer anticoagulants are less clear. In the US, agents available for oral anticoagulant reversal include activated prothrombin complex concentrate (APCC), 3-factor PCCs, and recombinant activated factor VII (rFVIIa). Few studies have evaluated the 3-factor PCCs, and current evidence for APCC and rFVIIa as reversal agents for dabigatran and rivaroxaban is based primarily on laboratory or animal studies, or on small studies in healthy humans and case reports. CONCLUSIONS: Patients contemplating using the new oral anticoagulants should be informed about specific clinical situations that could pose a bleeding risk such as the need for emergency surgery because no reliable antidote is available to stop the bleeding, which could prove fatal.

Using the Caprini Risk Score to Increase Awareness of Venous Thrombus Embolism in the Community: Know Your Score II.

To assess individual participants' baseline thrombosis risk calculated by Caprini Risk Score (CRS) before injury, illness, or hospitalization occur, to increase the awareness of venous thromboembolism (VTE) by viewing 2 short videos. A cross-sectional study was conducted online between August 2022 and January 2023 in the USA, UK, and India to assess the risk of thrombosis of individuals as a baseline. One nursing practitioner and 4 high school students were on the research team. Descriptive statistical methods were used in data analysis. A total of 928 usable completed questionnaires from 945 participants were analyzed. The mean CRS was 4.93 ± 3.175; 0 to 4 (N = 460, 49.6%), 5 to 8 (N = 394, 42.5%), and 9 (N = 74: 8.0%). History of blood clots (N = 247, 26.6%), <40 years old (N = 133, 52.6%); women on oral contraceptives (N = 324, 34.9%), history of smoking (30%), diabetes (26%), and inflammatory bowel disease (IBD; 17.3%). Top-level findings: High incidence of family history of thrombosis (26.6%), smoking, diabetes, contraceptives, and IBD. The average CRS (7.9) in patients over 75 years indicates that even a minor surgical procedure may be associated with significant VTE risk. We achieved an important goal by increasing awareness of VTE using this unique method involving high school students and a nurse working with friends and families to complete the CRS assessment. Encouraging the respondents to share information with their personal physicians prior to the event and keep these data in their medical file is a potential valuable source of saving time. This study emphasizes the importance of individuals collecting baseline information prior to illness or hospitalization.