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DVT Prophylaxis of the Medical Patient. Akella Chendrasekhar MD. Case. Mr. Smith- 71 y/o man admitted to general medicine ward service. HPI: gradually increased sob over 3 days assoc. with new productive cough, rhinorrhea, and fatigue. PMH: COPD, CHF (LVEF 35%), CRI (creat 2.5)
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DVT Prophylaxis of the Medical Patient Akella Chendrasekhar MD
Case • Mr. Smith- 71 y/o man admitted to general medicine ward service. • HPI: gradually increased sob over 3 days assoc. with new productive cough, rhinorrhea, and fatigue. • PMH: COPD, CHF (LVEF 35%), CRI (creat 2.5) • ROS: No h/o DVT/PE. • PE: VSS with SPO2 93% on RA • Barrel chested, b/l expiratory wheezes, prolonged expiratory phase, • CXR: hyperexpanded, no infiltrate, consolidation or edema. • DX: COPD Exacerbation
Does this patient need DVT prophylaxis? • Yes with LMW heparin • Yes with Heparin SQ BID • No, the risk of heparin complications is too high • I really don’t know
Does this man need DVT prophylaxis? • Why worry about VTE in inpatients? • What is the prevalence of DVT/PE in hospitalized medical patients? • Is this man at risk for venous thromboembolism? • What are effective methods of prophylaxis? • What adjustments need to be made based on his history of renal insufficiency?
Importance • What % of all hospital related deaths due to fatal PE? • 7-10% • What % of these pts had NO premorbid symptoms? • 70-90% • 200,000 potentially preventable annual deaths due to PE in the US Sandler DA JR Soc Med 1989; 82, Lindblad B Br Med J 1991; 302.
Prevalence in Medical Pts • 3 large-scale randomized studies (5500 medically ill patients) • DVT identified w/ screening studies • Patients receiving no prophylaxis: • VTE 11-15% of patients • Proximal DVT- 4-5% of patients • Rates similar to moderate-high risk general surgery patients. • Samana, MM NEJM, 1999; Leizorovicz, A Circulation 2004; Cohen, AT J Thromb Haemost, 2003.
Prevalence ACCP Guidelines, Chest. 2005.
Prevalence Pendleton, R. Amer J. Hematology 2005.
Prevalence • 3 out of 4 hospital pts dying from PE have NOT had recent surgery… • 2.5% of medical patients immobilized with multiple clinical problems suffer fatal PE. • National DVT Free Registry • 60% of patients dx with acute DVT were in the peri-hospitalization period • 60% of cases were in non-surgical patients! • Haas, S. Seminars in Thrombosis and Haemostasis, 2002; Goldhaber, SZ Am J Cardiol 2004.
Risk Factors • Heterogeneous population! • Need to consider: • Acute medical condition (MI, pneumonia, etc.) • Underlying risk factors (h/o VTE, estrogen use, etc.) • Medical interventions (central venous catheters, chemotherapy, etc.) • Relative contribution of various risk factors still being defined.
Risk Factors • Acute medical conditions well accepted as high risk: • MI (24% VTE risk) • Decompensated CHF (40% VTE risk) • Acute Stroke (30-75% VTE risk) • Spinal Cord Injury (up to 100%) • MICU admission (13-33*% VTE risk, *½ of these were proximal leg vein thromboses) • Central venous catheters (25-46% VTE risk) • Malignancy • Haas, S. Seminars in Thrombosis and Hemostasis, 2002; Pendleton, Amer J Hematology, 2005.
Current Rates of Prophylaxis • IMPROVE study • Ongoing multinational observational cohort study in acutely ill medical patients • Only 34% of potentially at risk patients are receiving any prophylaxis! • Only ½ of patients who would have met criteria used for MEDENOX study received any VTE prophylaxis. Anderson FA, IMPROVE; Blood 2003.
What Should We Use for Prophylaxis? • Mechanical compression devices? (compression stockings, IPC devices) • Unfractionated heparin BID? • Unfractionated heparin TID? • Low Molecular Weight Heparin? (Enoxaparin, Daltaparin) • Fondaparinux?
What Do We Know About Prophylaxis? • What are the most common regimens in the US? • UFH BID, mechanical compression devices • Which regimens have the least data to support them? • UFH BID, mechanical compression devices • What are characteristics of the ideal prophylaxis regimen? • Effective • Safe • Cost-effective
Key VTE Prevention Trials **MEDENOX study included 20 mg enoxaparin arm which was no more effective than placebo. Pendleton, R. Amer J. Hemat. 2005
*Remember that MEDENOX found enoxaparin 20 mg no more effective than placebo, therefore calling into doubt efficacy of bid heparin dosing.
Initial evaluation of DVT/PE risk in hospitalized surgical patients has become the standard of care. • As the patient is hospitalized and his/her condition evolves so does the DVT/PE risk.
Hypothesis • In the absence of changing level of care, the DVT/PE risk does change in hospitalized surgical patients.
Methods • Census based retrospective data analysis of 96 patients admitted to a 350 bed community hospital in Brooklyn, NY. • Hospital policy requires DVT/PE assessment of all patients upon admission. • Surgical patients DVT/PE risks were re-evaluated at variable times over a 1 month interval ranging from 1 day to 78 days post-admission. • This re-evaluation was done using the same hospital risk-assessment-score as was completed upon admission. • Risk assessment was performed using the hospital scoring system [1 = low risk, 2 = moderate risk, 3 = high risk, 4 = very high risk]. • Patients with DVT/PE were excluded from the analysis.
Data • Data was collected for 53 men, 43 women. • Gender did not correlate with DVT/PE risk. • Mean age: 60 years old.
Results • In the absence of changing level of care, 76/96 patients’ DVT/PE risk category changed as these patient’s were hospitalized. • Initial prophylaxis in the very high risk group was significantly lower compared to other groups. • The appropriateness of prophylaxis upon re-assessment was significantly reduced in ¾ risk groups.
Appropriateness of Prophylaxis Table 1: Statistical difference between Appropriateness of Initial vs. Re-assessment prophylaxis.
Figure 1: Appropriateness of Initial vs. Reassessment Prophylaxis.
Risk level change Figure 3: Risk level at Reassessment Figure 2: Risk level at Initial Assessment
Conclusion 1.) DVT/PE risk should be re-assessed on a regular basis as risk categorization frequently changes. 2.) High risk patients should be closely monitored as many are being under-treated.
What in the risk assessment caused the increase in risk for DVT?
Increase in risk factors seen • Sepsis • Increased from 60 % to 85 % day 23 • Planned major surgery change in risk • Change day 23 • Planned minor surgery change in risk • Day 1 2 • Duration of bed rest change in risk • Day 3 4
Complications of Prophylaxis • Bleeding • Major bleeding rates no different from placebo in major trials w/ enoxaparin, dalteparin, and fondaparinux (rates 0.2-1.7%) • HIT • Develops in 1.4% of medically ill pts exposed to preventive doses of UFH. • Potentially catastrophic- thrombosis rates as high as 60%. • LMWH’s 8-10X’s less likely to cause HIT. • Fondaparinux does not cause HIT. Girolami, B. Blood 2003; Warkentin TE, Br J Haematol 2003. Pendleton, R. Am J Hematol 2005.
When do we see the greatest risk of bleeding complications with prophylaxis? • Heart failure patients • Post surgical patients • Renal failure patients • I don’t know
Special Populations • Obesity • Renal Insufficiency • Elderly
Obesity • Anti Xa levels with fixed dose LMWH regimens correlate negatively with BMI in critically ill patients. (Priglinger U, 2003) • Standard prophylactic regimens twice as likely to fail in orthopedic pts with BMI >32. • BMI >32 VTE rate 32% vs 17% for BMI <32. (Samama, MM, 1995) • Non-randomized study in bariatric surg pts- suggested decreased DVT rates w/ enoxaparin 40 mg bid vs 30 mg bid. (Scholten, DJ, 2002) • No data to guide adjustments in therapy. • Options include: • Use standard dose • Add mechanical measures • Empiric dose adjustments
Renal Insufficiency • Delayed renal clearance of LMWH’s and Fondaparinux problematic. • Lack of outcomes based data. • FDA approved enoxaparin 30 mg qd for pts with creat clearance <30 ml/min based on pharmacokinetic data alone. • Additional options include UFH, mechanical devices.
Patients with HIT • Avoid UFH or LMWH’s. • Direct thrombin inhibitor- Argatroban to continue until platelet count increases to over 100 k • Remember thrombosis risk is still elevated even after stopping heparin.
Elderly Patients • Mahe et al. monitored anti-Xa levels in 68 consecutive hospitalized elderly patients (mean age 82) receiving enoxaparin for prophylaxis. • By day 2 over half had levels in the therapeutic range. • Lack of safety data with use of UFH as well. • Lack of outcomes data. • Consider empiric dose reduction or use of mechanical devices alone for elderly patients with low body weight and/or marginal creatinine clearance (30-60 ml/min). Mahe, I, Pathophysiol Haemost Thromb 2002., Pendleton R, Am J Hemat 2005.
Take Home Points • The majority of hospitalized medical patients are at increased risk for VTE. • In the absence of contraindicatons, prophylaxis should be provided for patients based on assessment of risks. • Risk changes during hospitalization and needs to be assessed. • Safe and Effective preventive regimens include: • Enoxaparin 40 mg SC daily • Daltaparin 5000 IU SC daily • Fondaparinux 2.5 mg sc daily • UFH 5000 units SC every 8hrs *Must use clinical judgement for unique patient groups with lack of data.