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Venous Thrombosis Prophylaxis. Joseph A. Caprini, MD, MS, FACS, RVT,DFSVS Emeritus, NorthShore University Health System, Evanston, IL Senior Clinician Educator, Pritzker School of Medicine, Chicago, IL. Disclosures.
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Venous Thrombosis Prophylaxis Joseph A. Caprini, MD, MS, FACS, RVT,DFSVS Emeritus, NorthShore University Health System, Evanston, IL Senior Clinician Educator, Pritzker School of Medicine, Chicago, IL
Disclosures I do not anticipate discussing the unapproved/investigative use of a commercial product/device during this presentation Janssen R&D - Steering Committee Pfizer - Bleeding Advisory Board BMS - Advisory Board Alexion Pharmaceuticals – Advisory board Recovery Force-Consultant
VTE Risk Factors1231 Patients Treated for VTE % of Confirmed DVTs 100 100 80 60 50 Objective Evidence of DVT (%) 36 40 24 20 11 0 3 1 2 4 5 Number of Risk Factors Anderson FA, et al. Circulation. 2003;107(Suppl 1):I9-I16.
Incidence of VTE Increases With Age 600 500 400 300 200 100 0 Male Patients Female Patients Incidence Rate per 100,000 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >80 Age Reprinted with permission from Anderson FA Jr, et al. Arch Intern Med. 1991;151:933-938.
Risk Assessment “I’m sorry, the CAT scanner is broken, so I’ll have to take your history and physical.”
Caprini Thrombosis Risk Scoring Caprini JA, Arcelus JI, Hasty JH, et al. Clinical assessment of venous thromboembolic risk in surgical patients. SeminThrombHemost 1991;17 Suppl 3:304-12. • Assign point value to risk factor – literature* • Total the points to obtain a score • Compare score to 30 day real VTE events • Obtain VTE rate for each score • Balance VTE rate vs. bleeding rate • Administer prophylaxis according to VTE rate • Type • Duration • Validate results for specific populations *Example Borow M, Goldson H. Am J Surg;141(2):245-251, 1981
Original Risk Assessment Model Widely used and validated worldwide including recent meta-analysis* *Pannucci CJ, Swistun L, MacDonald JK, Henke PK, Brooke BS. Ann Surg. 2017 Jan 19. [Epub ahead of print]
Validation of a Patient-Completed Caprini Risk Assessment Tool for Venous Thromboembolism Risk Assessment Fuentes HE, et al.
Validation of a Patient-Completed Caprini Risk Assessment Tool for Venous Thromboembolism Risk Assessment FIGURE 3. Bland Altman for patient-completed CRS FIGURE 2. Correlation for patient-completed CRS
Pitfalls Using The Patient Completed Form • Patients often fail to answer family history question correctly • Often do not understand BMI • Overlook pitting edema without finger pressure by examiner • History of obstetrical complications not fully understood • Patients may be carriers of the ACA or Beta2 abnormalities Healthcare provider reviews the patient form and makes sure the above factors are properly documented and a final admission score calculated
Completing The Score • Initial form completed by the patient • Healthcare professional checks form • Calculates initial score • Score revised during hospital stay reflecting – • Reoperation • Infection • Central lines • Cancer diagnosed during stay
Chart Reviews: Critical Evaluation 1 • Chart reviews depend on accuracy of the data collection • Missing data common • Were all the questions asked? • National Surgical Quality Improvement Program (NSQIP) • History of VTE, family history of VTE, Use, type, and duration of prophylaxis, ALL not recorded • Results in failure to separate very high risk patients as well as evaluate the effect of prophylaxis in the study group
VTE Risk is Underestimated by Chart Reviews Christopher Pannucci MD MS, Kory Fleming MPH, AVF 2016
Score Validated in a Variety of Populations Plastic surgery General surgery Head and neck Surgical ICU 17,000 validated patients in these four studies
Cassidy MR et al. J Am CollSurg 2014;218:1095-1104 Caprini scoring system success story based on mandatory standardized and required use including providing the patient with an adequate length of prophylaxis based on the level of risk Mandatory selection of prophylaxis required before the patient orders can be signed Length of prophylaxis mandated according to score
100% 100% 100% 89% 77%
Mandatory ComplianceCritical Evaluation 2 Mandatory compliance for prophylaxis protocols based on risk score linked to level of risk must occur for these protocols to having a lasting effect lowering the VTE rate The physician always has the opportunity to OPT OUT for valid clinical concerns
Caprini Scores in Patients Not Receiving Prophylaxis Pannucci CJ, Swistun L, MacDonald JK, Henke PK, Brooke BS. Ann Surg. 2017 Jan 19. [Epub ahead of print]
Individualized Venous Thromboembolism Risk Stratification Using the 2005 Caprini Score to Identify the Benefits and Harms of Chemoprophylaxis in Surgical Patients: A Meta-analysis This meta-analysis is just a start and there are EXCEPTIONS notably hematologic based or venous flow-related risk factors Pannucci CJ, et al. Ann Surg; 2017; 265(6):1094-1103 • Caprini scores 6 or less = 75% of patients • No significant reduction in VTE using prophylaxis • Suggest mechanical prophylaxis except for hematologic risk factors • Minimizes bleeding risk in these patients • Caprini scores of 7 to 8, and scores >8 • Statistically significant VTE risk reduction postoperatively using anticoagulants
Randomized Clinical Trial Data Vs.Real World Experience Critical Evaluation 3 CHEST 2008; 133:381S–453S 1.4.5 Application of Evidence to Individual PatientsSince most thromboprophylaxis studies excluded patients who were at particularly high risk for either VTE or adverse outcomes, their results may not apply to those with previous VTE or with an increased risk of bleeding. In these circumstances, clinical judgment may appropriately warrant use of a thromboprophylaxis option that differs from the recommended approach. ESPECIALLY PAST HISTORY OR FAMILY HISTORY OF VTE
The Rate of Bleeding Complications After Pharmacological DVT Prophylaxis *Bleeding incidence not trivial NO DEATHS 5.5 33 RCTs in 33,000 patients 4.0 3.4 Complications (%) 3.3 2.6 2.0 1.9 1.8 1.0 0.8 0.7 NA Leonardi MJ, et al. Arch Surg. 2006;141:790-9
Bleeding Vs. ThrombosisCritical Evaluation 4 Postoperative Death From Bleeding Using Prophylactic Doses Of Anticoagulants Is VERY RARE Withholding Anticoagulation In Surgical Patients Is Associated With An Increased Incidence Of Fatal VTE
Prophylaxis Against Fatal PE With Low-dose UFH4,121 Patients Undergoing Major SurgeryPrimary End-point: Fatal PE p < 0.005 18 16 16 14 12 Control Number of patients with fatal PE 10 UFH 8 UFH = unfractionated heparin 6 4 2 2 0 Low-dose UFH Saves 7 Lives For Every 1,000 Operated Patients. Kakkar VV, et al. Lancet. 1975;2:45-51.
Death From PE But Not Death From Bleeding Collins R, et al. N Engl J Med. 1988;318:1162-73. Seventy Evenly Randomized Trials Of Perioperative S.C. Heparin In General, Orthopedic, And Urological Surgery Fatal bleeds “Other”deaths PE 250 223 (3.5) Fatal events 210 (3.3) Non-fatal events 200 191 (3) Heparin (H), n = 6,386 Number of subjects affected, n (%) 150 Control (C), n = 6,246 109 (1.7) 100 50 7 (0.1) 6 (0.1) 19 (0.3) 55 (0.9) C H C C H H Prophylaxis Continued For One Week
Fatal Pulmonary Embolism in Surgical Patients • Randomized Double-blind Comparison Of LMWH With UFH, Involving 23,078 Surgical Patients Given Prophylaxis 5-20 Days (Sixty-seven Centers) Haas S, et al. ThrombHaemost. 2005;94:814-9. Anticoagulant prophylaxis reduces the risk of death to 0.15% No deaths from anticoagulant bleeding Excessive perioperative and postoperative blood loss occurred in 0.13% [95% CI 0.06, 0.18] of LMWH patients compared with 0.20% [95% CI 0.12, 0.28] of the UFH treated patients (P=0.19).
CHEST 2012; 141(2)(Suppl):e227S–e277S • 2.5 LMWH vs LDUH • Meta-analysis of 51 randomized controlled trials compared LMWH and LDUH in 48,000 general and abdominal surgery patients • In most studies, follow-up was for either 7 days or 1 month • The risk was 30% lower in the LMWH groups • CHEST authors did not emphasize providing prophylaxis for one week despite the fact that this period was shown to be efficacious in the 51 trials used to provide the above conclusion • Since 2012 edition was published • The Boston success story further illustrate the importance of providing at least 7 days of prophylaxis to patients who are “At Risk”
Length Of ProphylaxisCritical Evaluation 5 SHORT COURSES OF ANTICOAGLANT PROPHYLAXIS MAY SERIOUSLY COMPRIMISE EFFICACY • From 1975 to 2005 • 43,000 patients (160 centers) • Objective diagnostic endpoints • Anticoagulant prophylaxis for ONE WEEK established efficacy
Altom LK, Deierhoi RJ, Grams J et al. Am J Surg. 2012;204:591–597 Study evaluated SCIP-VTE adherence for 30,531 operations from 2006 to 2009 linked with VA Surgical Quality Improvement Program data 89.9% of the patients adhered to the SCIP-VTE measure and 1.4% suffered a VTE event The incidence of VTE events in those not complying with the SCIP-VTE mandate was 1.3% The authors concluded that there was no association between SCIP-VTE adherence and the incidence of postoperative VTE
Effect Of A Near-Universal Hospitalization-Based Prophylaxis Regimen On Annual Number Of Venous Thromboembolism Events In The USA Heit JA, et al: Blood. 2017;130(2):109-114 • “Approximately 500 000 US VTE events annually • Half related to hospitalization • VTE event rates (2005-2010) unchanged • Near universal in-hospital VTE prophylaxis • possibly due to short prophylaxis duration” • Mean duration 70 hours • Conclusions • A short course of anticoagulants is ineffective in lowering the VTE rate • Identify high risk patients that would benefit from extended prophylaxis
Surgical Care Improvement Project (SCIP): Has Its Mission Succeeded?? The rate of PE increased from 0.87% to 1.30% (P = 0.002). Our findings indicated that SCIP has not been successful in reducing complications in TJA patients Rasouli MR, et al. J Arthroplasty.2013;28:1072–1075
Discordance Between SCIP Adherence and Postoperative Outcomes J Surg Res. 2017;212:205-213 • Patients = 779,922 followed for 30 days over 5 yrs. • SCIP VTE-1, -2 adherence improved by 14.6% and 20.2%, respectively during the 5 years • Postoperative DVT rate increased by 7.1% Postoperative PE rate increased by 3.7% • Short-term anticoagulant prophylaxis postoperatively DOES NOT lower the VTE rate • Lowering the VTE rate after surgery requires at least ONE week as shown in more than 140 studies done over the last 40 years
Time Course and Clinical Presentation of Postoperative VTE in Registry Data HIGH CAPRINI SCORES RECEIVE EXTENDED PROPHYLAXIS 800 700 PE Distal DVT Proximal DVT 77% 600 RIETE: Computerized Registry of Patients with Venous Thromboembolism 55% of VTEs were diagnosed after prophylaxis was discontinued 500 Cumulative incidence 400 300 19% 200 100 0 0 5 10 15 20 25 30 35 40 45 50 55 60 Days Arcelus JI, et al. ThrombHaemost. 2008;99:546-51
When Do Pulmonary Emboli Occur? Total PEs were 6,624 out of 2,001,405 patients: NSQIP Database:2011-2013 2013: (2,130 PEs out of 651,940 patients) Marangoni, Jim: Legacy Good Samaritan Medical Center
CHEST guidelines considered history of thromboembolism in the highest risk group of patients along with cancer and indicate that the risk of thrombosis is 40-80% with a 1.0-5.0% chance of a fatality 2004 CHEST 2004; 126:338S–400S, Table 5 page 341S
(Grade 1A). For Selected High-risk General Surgery Patients, Including Some Of Those Who Have Undergone Major Cancer Surgery Or Have Previously Had VTE, We Suggest That Continuing Thromboprophylaxis After Hospital Discharge With LMWH For Up To 28 Days Be Considered (Grade 2A) 2008 CHEST 2008; 133:381S–453S
CHEST 2.6 Extended- Vs Limited-duration LMWH (2012 Guidelines) Critical Evaluation 6 What Happened To The CHEST Recommendations Of 2004, 2008 Recommending Extended Prophylaxis For Those With Past History Of VTE ?? Bottaro FJ, Elizondo MC, Doti C, et al. Efficacy of extended thrombo-prophylaxis in major abdominal surgery: what does the evidence show? A meta-analysis. ThrombHaemost. 2008;99(6):1104-11 The risk of VTE remains elevated for at least 12 weeks following surgery Three studies cited by CHEST including one meta-analysis in patient having Surgery for benign and malignant disease All three analyses concluded that extended-duration prophylaxis reduced the risk of symptomatic or asymptomatic DVT by at least 50%, and two reported that proximal DVT was reduced by 75%. (Bottaro)
Ambulation has NO effect on existing risk factors such as cancer and history of VTE and only decreases the risk associated with immobilityThe statement that anticoagulant prophylaxis should be continued until the patient is ambulatory is not data based Critical Evaluation 7
Conclusions • Risk assessment using the Caprini score • Utilize patient- friendly form +verification • Avoid chart review • Face-to-face critical • Provide prophylaxis for at least one week in those “at risk” - Score > 5 • Appropriate prophylaxis for “at risk” patients cannot be discontinued just because the patients becomes ambulatory
Conclusions Anticoagulant prophylaxis does not causes bleeding deaths but SAVES lives Extend prophylaxis for at least 28 days (Cancer, Joint replacement, Prior VTE) and/or Score >8 Continue prophylaxis for as long as risk is ongoing (Immobilization, infection, casts, rigid leg braces, etc.) Pay very careful attention to personal and family history of VTE in first, second, and third degree relatives