#12 DVT Prophylaxis in the Critically Ill
Every time we admit or care for a critically ill patient, we must consider their risk for deep venous thrombosis, or DVT. Many of our patients are at higher risk for DVT than the general population, but anticoagulants are not wholly benign drugs. What do we do? How do we decide who to treat medically, who to treat with mechanical compressive devices and identify patients who may NOT need anything? When do risks out-weight benefits? What agent is best?Join Nick and Cyrus as they interview hematologist & oncologist Dr. Matthew Rendo (Twitter/X: @Rendoncology) as they do a deep dive into managing DVT prophylaxis in the critically ill patient!
Quick Take Home Points:
The risk of VTE in critical illness is high. PE is the most common cause of preventable hospital death.
Prophylaxis substantially reduces the risk of VTE. Chemoprophylaxis dramatically reduces the incidence of DVT in ICU patients, but it carries a risk of bleeding. Mechanical prophylaxis is less effective than chemoprophylaxis.
In patients with creatinine clearance >30, LMWH is superior to UFH.
Thrombocytopenia is not protective against VTE but does increase the risk of bleeding with chemoprophylaxis.
Trauma patients are at higher risk for VTE; generally a higher dose of LMWH is recommended.
Holding chemoprophylaxis before procedures depends on the procedure and agent. For many ICU procedures (central line, arterial line, thoracentesis, paracentesis) it is unnecessary to hold prophylaxis.
Risk prediction models (e.g. PADUA, Capri) can be used to individualize therapy based on patient risk factors.
Infographic:
Show Notes:
The risk of VTE in people with critical illness is substantial.
PE is believed to be the most common preventable cause of death among hospitalized patients.
Among people who die in the ICU, 7-27% have a PE on autopsy. It is difficult to diagnose PE in the critically ill, so it is probably significantly under-diagnosed.
Chemoprophylaxis dramatically reduces the incidence of DVT in ICU patients, but it carries a risk of bleeding.
Several options for chemoprophylaxis:
Un-fractionated Heparin (UFH) - naturally occurring polysaccharide that inhibits coagulation. Contains polysaccharides of varying lengths.
Low Molecular Weight Heparin (LMWH) - fractionated heparin that contains shorter polysaccharides, providing more predictable pharmacokinetics.
Fondiparinux - synthetic penta-saccharide chemically similar to LMWH, lower risk of HITT
In meta-analyses, 13-32% of people who do not receive prophylaxis develop DVTs compared to 5-9% of those receiving heparin.
ARTEMIS trial: Fondaparinux vs. placebo in critically ill.
VTE: 11% (placebo) vs 6% (Fonda), NNT= 20.
No increase in major bleeds (1 in each group).
LMWH vs. placebo (meta-analysis of 8 trials) showed risk of DVT decreased by 42% and NNT of 46. Minor bleeding with LMWH had NNH of 45
LMWH probably superior to UFH for chemoprophylaxis
Meta-analysis of 36 trials of all-comers, LMWH vs. UFH: lower risk DVT w/ LMWH > UFH (RR 0.68) without differences in bleeding risk.
In people with CrCl<30, UFH should be used.
Other chemoprophylaxis options:
Direct Oral Anti-Coagulants (DOACs) - meta-analysis of 3 large studies suggests possibly a small benefit in VTE reduction, but ~2x higher risk of major bleeding. Invetigational (not routinely used) and not advised.
Aspirin (ASA) - good for reducing major arterial thrombotic events, but limited evidence for any antiplatelet agent in VTE prevention in hospitalized medical patients. Not advised.
Warfarin - takes 1.5-3 days to reach therapeutic INR, medical comorbidities may interfere (liver dysfunction). Not advised
Mechanical prophylaxis reduces the risk of DVT without any increase in bleeding risk but is probably less effective than chemoprophylaxis.
Intermittent pneumatic compression (IPC)
CLOT3 trial: IPC vs. no device, 30d VTE rate 8.5% vs 12%
Combining IPC + chemoprophylaxis does not appear to confer significant additional risk reduction.
PREVENT trial: 2003 critically ill patients, 80% MICU pts w/ intermittent pneumatic compression for at least 18 hours+ UFH or LMWH: did not statistically reduce the rate -US-detected DVT 3.9vs4.2% or symptomatic PE 0.8vs1% or death of any cause
Risk of VTE can be assessed using the PADUA score; this can help determine the need for chemoprophylaxis vs mechanical prophylaxis.
PADUA score can be used in general medical patients.
Caprini model can be used in assessment of VTE risk in adult general surgical patients and uses age, comorbidities, recent surgeries, obesity, smoking, cancer, length of hospitalization, type of truama, etc with scores >5 indicative of high VTE risk.
Is it safe to give chemoprophylaxis in people with thrombocytopenia?
Thrombocytopenia increases bleeding risk but does not necessarily protect against VTE. It is important to weigh the risks and benefits of chemoprophylaxis for thrombocytopenic patients.
Confirm that thrombocytopenia is real: use citrate (blue top) tube + manual differential to exclude clumping, make sure giant platelets not being counted as RBCs
In general, give chemoprophylaxis if platelets are > 50k
Use mechanical prophylaxis if platelet count 30-50k
Use PADUA score to assess individual risk
In patients who develop thrombocytopenia, it is important to consider heparin as a potential cause.
Use 4T score to assess the risk for HITT
Should we hold heparin prophylaxis before procedures or delay procedures while heparin washes out?
For many bedside procedures, the bleeding risk is low enough and the urgency is high enough that you shouldn’t wait 12-24hr. (e.g. a septic patient who needs venous access for vasopressors)
Rate of major bleeding from a thora <0.2% even while on prophylactic AC
No data to support testing coags before a paracentesis.
For LPs, you should hold AC. Duration depends on the agent:
UFH 4-6hr
LMWH 12hr
Fondaparinux 24hrs
DOACs 24hr
Trauma patients are at higher risk of VTE. VTE prophylaxis is especially important in this population.
Meta-analysis indicates that LMWH or LMWH + mechanical compression should be used
Mechanical vs. no PPX: 5 trials RR 0.43
pharmacologic vs. mechanical PPx: six trials RR 0.48 with higher risks for minor BUT not major bleeding
LMWH vs. UFH: LMWH>UFH for reducing DVT risk in 2 separate trials (RR.68) with similar bleeding rates
Combined mechanical +pharmacologic PPx vs. pharm PPx alone: 3 trials showed reduced risk (RR 0.34)
A higher dose of LMWH is often used in trauma patients:
LMWH 40mg q12
w/ adjustment based on anti-Xa levels targeting peak .2-.4 & trough .1-.2
-weight based: .5mg/kg q12 targeting same anti-Xa levels
Timing of DVT PPX following thrombolytics?
Acute ischemic stroke and thrombolytics: high risk due to restricted mobility, SCDs/IPCs often started at time of admission, but AC delayed until 24hrs post thrombolytics
No IV thrombolytics: SCDs + Low dose heparin (UFH/LMWH) added for patients not being treated with DAPT
Audio
Video
-
Cohen et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ. 2006
Dumaine et al. Intravenous Low-Molecular-Weight Heparins Compared With Unfractionated Heparin in Percutaneous Coronary Intervention: Quantitative Review of Randomized Trials. Arch Intern Med. 2007
Neumann et al. DOACs vs LMWHs in hospitalized medical patients: a systematic review and meta-analysis that informed 2018 ASH guidelines. Blood Advances 2020
Arabi et al. Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. NEJM 2019
Barbar et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010
-
-