3. Bundles
• PE third most common cause of iatrogenic
death.
• 2001 AHRQ report emphasized 1A evidence
• IHI 5 million lives campaign—VAP bundle
4. LE DUS for PE
• 90% PE’s originate in lower extremity
• 1st symptomatic DVT
– Sensitivity 95%, specificity 96%
– Increased sensitivity:
• serial US at 5-7 days
• combining with clinical suspicion
6. Risk Factors for DVT
Surgery
Trauma (major or lower extremity)
Immobility
Paresis
Malignancy
Cancer therapy (hormonal, chemotherapy, or radiotherapy)
Previous VTE
Increasing age
Pregnancy and the postpartum period
Estrogen-containing oral contraception or hormone replacement therapy
Selective estrogen receptor modulators
Acute medical illness
Heart or respiratory failure
Inflammatory bowel disease
Nephrotic syndrome
Myeloproliferative disorders
Paroxysmal nocturnal hemoglobinuria
Obesity
Smoking
Varicose veins
Central venous catheterization
Inherited or acquired thrombophilia
7. Risk of DVT
DVT Prevalence,
Patient Group %
Medical patients 10–20
General surgery 15–40
Major gynecologic surgery 15–40
Major urologic surgery 15–40
Neurosurgery 15–40
Stroke 20–50
Hip or knee arthroplasty, hip fracture surgery 40–60
Major trauma 40–80
Spinal cord injury 60–80
Critical care patients 10–80
Geerts et al.Chest, 2004;126:338S
8. Inherited Hypercoagulability
Prevalence Population
DVT Prevalence
Factor V Leiden 12-21%** 6%
Prothrombin mut 6-8% 2%
Protein C, S def 2-4% < 1%
AT III def 1-2% <1%
All Thrombophilia 24-37% 10%
**OR 5.9 (CI 2-18) for breakthrough
Albrecht. Online 2007
Baba Ahmed. Thromb Haemost 2007; 97: 171
10. Overview
Mechanical Compression
• No convincing evidence of mortality value over placebo.
Plantar vs. Calf
• DVT in 21.0% plantar vs. 6.5% calf (p = 0.009).
Knee-length vs. Thigh-length
• Equivalent effect w improved compliance in KL group.
Mechanical vs. Chemical
• OR 0.46 (CI 0.16-1.29) for all heparin vs. mechanical
Gregory et al. J Trauma 1999; 47:1
14. Overview
Aspirin
• Not recommended for DVT prophylaxis
• Aspirin vs. LMWH
• 63% RRR among 205 ortho pts LMWH vs. ASA.
• Among hip trauma pts, 44% vs. 28% ASA vs. LMWH
UFH and LMWH
• UFH decreases incidence of DVT by 20% over placebo
• LMWH decreases incidence of DVT by 30% over UFH.
15. Mechanism of Heparins
Unfractionated heparin
inactivates both Factor IIa
and Xa
LMWH has increased affinity
for Factor Xa
Fondiparinux is only a
pentasaccharide sequence
Weitz. NEJM, 1997; 337:688
18. LMWH vs. UFH 2
Dolovich, L. R. et al. Arch Intern Med 2000;160:181-188.
19. LMWH vs. UFH 3
Dolovich, L. R. et al. Arch Intern Med 2000;160:181-188.
20. LMWH vs. UFH in Trauma
Atia et al. Arch Intern Med 2001; 161: 10.
21. LMWH vs. UFH in Trauma
• Double blind, RCT
• 344 major trauma—no ICH
• 1st dose within 36 hours of injury
• No mechanical prophylaxis
• 5000 U LDUH v. 30 mg enoxaparin BID
• RRR DVT 30% for LMWH
• Higher bleeding in LMWH, but not
significant
Geerts et al. NEJM 1996
23. LMWH
Advantages Disadvantages
• Longer half life • Poor protamine
• Improved efficacy response (60%)
• Less heparin-induced • Variable effect w
thrombocytopenia renal failure, obesity
• Cost-effective for • Concern for
trauma and gen surg bleeding
24. DVT Recommendations
DVT, % PE, %
Level of Risk Successful Prevention Strategies
Calf Proximal Clinical Fatal
Low risk 2 0.4 0.2 <0.01
Minor surgery in patients < 40 yr No specific prophylaxis; early and "aggressive"
with no additional risk factors mobilization
10– 0.1–
Moderate risk 20 2–4 1–2 0.4
Minor surgery in patients with risk
factors LDUH (q12h), LMWH ( 3,400 U daily), GCS, or IPC
20– 0.4–
High risk 40 4–8 2–4 1.0
Surgery in patients > 60 yr LDUH (q8h), LMWH (> 3,400 U daily), or IPC
40–
Highest risk 80 10–20 4–10 0.2–5
Surgery in patients with multiple LMWH (> 3,400 U daily), fondaparinux, oral VKAs
risk factors, Trauma, Ortho (INR, 2–3), or IPC/GCS + LDUH/LMWH
Geerts et al. Chest, 2004; 126:338S
26. IVCF Reasons for Use
• Clot with active cerebral bleeding
• Clot despite anticoagulation
• Massive PE with chronically compromised
pulmonary vasculature
27. IVCF Effectiveness
Filter No filter p
PE at day 12 1% 5% 0.03
PE at 2 years 3% 6% NS
DVT at 2 years 21% 12% 0.02
Death 22% 21% NS
Major bleed 9% 12% NS
DeCousus et al. NEJM 1998; 338:409
29. DVT Recommendations
DVT, % PE, %
Level of Risk Successful Prevention Strategies
Calf Proximal Clinical Fatal
Low risk 2 0.4 0.2 <0.01
Minor surgery in patients < 40 yr No specific prophylaxis; early and "aggressive"
with no additional risk factors mobilization
10– 0.1–
Moderate risk 20 2–4 1–2 0.4
Minor surgery in patients with risk
factors LDUH (q12h), LMWH ( 3,400 U daily), GCS, or IPC
20– 0.4–
High risk 40 4–8 2–4 1.0
Surgery in patients > 60 yr LDUH (q8h), LMWH (> 3,400 U daily), or IPC
40–
Highest risk 80 10–20 4–10 0.2–5
Surgery in patients with multiple LMWH (> 3,400 U daily), fondaparinux, oral VKAs
risk factors, Trauma, Ortho (INR, 2–3), or IPC/GCS + LDUH/LMWH
Geerts et al. Chest, 2004; 126:338S
30. Trauma Recs
Trauma patients with at least one risk factor for VTE receive thromboprophylaxis, if possible (Grade 1A).
In the absence of a major contraindication, LMWH prophylaxis starting as soon as it is considered safe to do so (Grade 1A).
Mechanical prophylaxis with IPC be used if LMWH prophylaxis is delayed or if it is currently contraindicated due to active
bleeding or a high risk for hemorrhage (Grade 1B).
DUS screening in patients who are at high risk for VTE (eg, SCI, lower extremity or
pelvic fracture, major head injury, or an indwelling femoral venous line,
suboptimal prophylaxis) (Grade 1C).
No use of IVCFs as primary prophylaxis in trauma patients (Grade 1C).
Continuation of thromboprophylaxis until hospital discharge, including the period of
inpatient rehabilitation (Grade 1C+).
Continuing prophylaxis after hospital discharge in patients with major impaired
mobility (Grade 2C).
35. Thank you.
Thanks to pt. DW for worrying me about this issue every day for a week.
36. Clinical Probability of PE
Leg swelling, tenderness 3
Pulse > 100 1.5
Immobilization, surgery 1.5
Prior DVT/PE 1.5
Hemoptysis 1
Cancer 1
No other more likely Dx 3
< 2 = Low probability 2-6 = Moderate > 6 = High
Wells, Ann Intern Med 2001
Notas del editor
90%. … AND studies show that 40% patients presenting with PE who have NO leg symptoms have a DVT if you look for it. Dx = noncompressibility of a deep vein Serial US if sx persist: identify 1-2% w/ DVT missed on initial study.
50% prox DVTs embolize to lung. 20% calf vein DVTs embolize to prox veins, meaning that only 10% cause PE. In trauma pts, 1/3 to ½ of dvts are proximal. Study has shown that PCPs misinterpret US results diagnosing superficial femoral clot as unimportant. Most studies of VTE and its prevention have used sensitive diagnostic tests to detect DVT. The majority of the thrombi diagnosed by these screening tests were confined to the calf, were clinically silent, and remained so without any adverse consequences. 22 23 24 25 However, approximately 10 to 20% of calf thrombi do extend to the proximal veins, 22 26 27 28 29 30 and, particularly in patients undergoing major surgery involving the hip, isolated femoral vein DVT is common. 31 32 33 34 There is also a strong association between asymptomatic DVT and the subsequent development of symptomatic VTE. 22 35 36 37 38 39 40 41 42 For example, one study 42 found that among critical care patients with asymptomatic DVT detected by screening DUS there was a significantly greater rate of PE development during their index hospitalization compared to those patients without silent DVT (11.5% vs 0%, respectively; p = 0.01). Furthermore, the in-hospital case-fatality rate of VTE is 12%, 12 and the data suggest a case-fatality rate at 1 year of 29 to 34%. 12 43
If you look for a source Among all pt’s with clot, 24-37% have thrombophilia, vs. 10% of the general pop (w/ clot, 80% of all comers have a cause acquired or genetic) FV Leiden - 5-6% of Whites, rare in Asian, AA. Causes resistance to protein C. Lifetime risk of clot increased 2.2X (vs. Pro C, S 7-8X) inc risk by 4-10 in heterozygotes Prothrombin mutation: leads to PT levels 30% higher than controls Homocystein - due to genetic abnormality most commonly of MTHFR enzyme, or deficiency of B6, B12, or folic acid About 1/3 w/ SLE have ACLA and 1/3 have LA Half w/ SLE and APS will clot Also, elevated F8 level >150% nl, linked to blood group other than 0, presumed genetic 50-60% of inherited thrombophilia is due to FV Leiden or the Prothrombin mutation
Among 205 patients undergoing hip or knee arthroplasty, who were randomized to receive aspirin or the LMWH ardeparin, the relative reduction in the risk of VTE with the use of LMWH over aspirin was 63% (p < 0.001).157 The RRRs for DVT and proximal DVT in patients who have received prophylaxis with a VFP plus aspirin over that with aspirin alone following total knee arthroplasty (TKA) were 32% and > 95%, respectively (p < 0.001 for both comparisons).156 Among hip fracture surgery (HFS) patients who were randomized to receive either aspirin or danaparoid, a low-molecular-weight heparinoid, VTE was detected in 44% and 28% of the patients, respectively (p = 0.028).158
We commonly use US as a diagnostic test for DVT, but how good is it as a diagnostic test for PE? 90%. … AND studies show that 40% patients presenting with PE who have NO leg symptoms have a DVT if you look for it. Dx = noncompressibility of a deep vein Serial US if sx persist: identify 1-2% w/ DVT missed on initial study.
We commonly use US as a diagnostic test for DVT, but how good is it as a diagnostic test for PE? 90%. … AND studies show that 40% patients presenting with PE who have NO leg symptoms have a DVT if you look for it. Dx = noncompressibility of a deep vein Serial US if sx persist: identify 1-2% w/ DVT missed on initial study.
Among 205 patients undergoing hip or knee arthroplasty, who were randomized to receive aspirin or the LMWH ardeparin, the relative reduction in the risk of VTE with the use of LMWH over aspirin was 63% (p < 0.001). 157 The RRRs for DVT and proximal DVT in patients who have received prophylaxis with a VFP plus aspirin over that with aspirin alone following total knee arthroplasty (TKA) were 32% and > 95%, respectively (p < 0.001 for both comparisons).156 Among hip fracture surgery (HFS) patients who were randomized to receive either aspirin or danaparoid, a low-molecular-weight heparinoid, VTE was detected in 44% and 28% of the patients, respectively (p = 0.028).158
Enoxaparin has 10a to 2a ratio of 3.8, which is highest.
Most difference found because of dalteparin and nadroparin. Made by: Pfizer and Sanofi. Lovenox is Sanofi as well.
Bleeding among general surgery. No study in trauma patients of bleeding complications.
GFR < 30, decrease dose to weight based from 1 mg/kg SQ bid to qd, for prevention 30 qd. Not FDA approved for HD pts. Weight limit enoxaparin 144 kg. The incremental cost of enoxaparin relative to UH was C$90, and the incremental effectiveness was 0.085 DVTs averted and -0.13 LYG. This resulted in an incremental cost-effectiveness ratio of C$1,059 per DVT averted, and the conclusion that UH is the dominant strategy in terms of LYG. UH remained the dominant strategy in terms of life years independent of the parameter estimates because of increased bleeding in the LMWH. Shorr 2001, CCM. DVT with LDH was 14.7%, that LMWH resulted in a relative risk reduction of DVT of 50%, but that enoxaparin nearly quadrupled the risk of bleeding. Despite the higher costs of enoxaparin, this tactic yielded a net savings of $391.23 per DVT prevented.
Value of risk stratification. Low risk = ambulatory surgery High risk: elderly, ortho, cancer, or multiple other risks
400 patients with proximal DVT, 50% with PE. Also repeated to show equivalence
Low risk = ambulatory surgery High risk: elderly, ortho, cancer, or multiple other risks
Hospital admissions on or after January 1, 2001, and concluded by March 31, 2005, were included if they met any of the following conditions as defined in the ACCP Consensus Conference on Antithrombotic Therapy guidelines
Exponential increase DVT diagnosis after 4 days. 3 times risk of finding DVT if waiting more 4 days. Logistic regression shows LE injury improves use.