PROPHYLAXIS FOR DVT & PE

See also  "Deep Vein Thrombosis" and "Pulmonary Embolus"

I. Indications: prolonged immobilization e.g. during hospitalization

II. Mechanical methods

  1. Graduated compression stockings
  2. Intermittent pneumatic compression boots
    1. In a study of 131 pts undergoing total hip- or knee replacement, all of whom received enoxaparin x 30d, and who were randomized to intermittent pneumoatic compression calf boots (from intraop to 10d post-op) vs. graded compression stockings (from intraop to 3mos postop), the pneumoatic-compression pts had sig. lower incidence of DVT (on duplex ultrasound which was done on all pts) 6-12d after surgery (0% vs. 29%); no pts had documented pulmonary embolism in first 12wks post-op (J. Bone Joint Surg. Br. 86:809, 2004--JW)
  3. Intermittent compression foot-pump
  4. Inferior vena caval filter

III. Pharmacologic methods:

  1. In a meta-analysis of nine randomized trials of anticoagulant prophylaxis for DVT for medical inpatients, prophylaxis was associated with sig. lower incidence of sympomatic DVT (0.38% vs. 0.81%) and fatal PE (0.14% vs. 0.39%) but no sig. diff. in mortality (Ann. Int. Med. 146:278, 2007--JW)
  2. Unfractionated low-dose SQ heparin 5000U Q8-12h
  3. Low molecular weight heparin
    1. 866 pts > 40yo hosp'd with nonsurgical conditions randomized to enoxaparin 20mg QD, enoxaparin 40mg QD, or placebo, all x 6-14d; all got venography at end of tx. Sig. less DVT in 40mg enoxaparin group c/w placebo (5.5% vs. 14.9%)--no sig. diff. between placebo and 20mg enoxaparin group (NEJM 341:793, 1999--JW)
    2. In a randomized trial in 3,706 pts > 40yo hospitalized with an acute illness for > 4d, dalteparin 5kIU SQ QD vs. placebo x 14d was ass'd with sig. lower 21-day incidence of suddent death or venous thromboembolism (2.77% vs. 4.96%); no sig. diff. in overall 90-day mortality ("PREVENT" Trial; Circ. 110:874, 2004--JW)
    3. Efficacy at DVT prevention in post-operative pts similar to SQ Heparin (see above)
    4. Duration of treatment when used post-op
      1. In a systematic review of 6 randomized trials of low-molecular-weight heparin vs. placebo after discharge for hip arthroplasty, LMWH was ass'd with sig. lower risk for all DVT and symptomatic DVT; no diff. in risk of major or minor pleeding (Ann. Int. Med. 135:858, 2001--JW)
      2. 1mo ass'd with lower DVT incidence than 7-10d of LMWH tx in pts after hip replacement (NEJM 335:696, 1996--JW) and after cancer surgery (NEJM 346:975, 2002--JW)
    5. Compared with warfarin--better prevention; more bleeding
      1. 349 pts w/p total knee replacement randomized to Enoxaparin 30mg SQ BID vs. warfarin (adjusted to INR 2.0-3.0); all pts had bilateral LE u/s and unilateral venography (on the surgical side); Incidence of DVT was significantly lower with enoxaparin (25% vs. 46%); ditto for proximal DVT (2% vs. 11%). Enoxaparin had sig. more clinically important hemorrhage (34% vs. 23%) and nonsig. higher incidence of major hemorrhage (5% vs. 2%) (J. Bone Joint Surg. Am. 83A:900, 2001--JW)
  4. Fondaparinux (a synthetic heparin analogue)
    1. Comparisons with LMWH
      1. In a randomized trial of 2309 pts undergoing total hip replacement randomized to fondaparinux 2.5mg SQ QD starting 6h postop vs. enoxaparin 40mg QD starting 12h preop, both continued until 5-9d postop, venous thromboembolism (on venography at 5-11d postop) sig. lower with fondaparinux (4% vs. 9%) but major bleeding incidence was nonsig. increased in fondaparinux pts (4% vs. 3%) (Lancet 359:1715, 2002--JW)
      2. In a randomized trial of 2275 pts undergoing total hip replacement randomized to fondaparinux 2.5mg SQ QD starting 6h postop vs. enoxaparin 30mg BID starting 12-24h postop, incidence of venous thromboembolism was not sig. diff. between the groups, though symptomatic venous thromboembolism sig. more common in the fondaparinux pts; fondaparinux pts had nonsig. increased risk of major bleeding (Lancet 359:1721, 2002--JW)
      3. More effective than enoxaparin for DVT prophylaxis but sig. more likely to be ass'd with both major and minor bleeding) in pts undergoing hip replacement surgery (NEJM 344:619, 2001--JW; NEJM 345:1298, 2001--JW;  NEJM 345:1305, 2001--JW)
      4. In a re-analysis of ata from four randomize trials of fondaparinux vs. enoxaparin for prophylaxis of venous thromboembolism in pts undergoing major hip or knee surgery or surgery for a proximal femoral fx, fondaparinux recipients had sig. lower incidence of (proximal DVT or PE) (1.7% vs. 3.3%) and (proximal DVT, symptomatic PE, or death) (2.1% vs. 3.9%) (Chest 126:501, 2004--AFP)
  5. Warfarin
    1. Adjusted-dose coumadin (for ortho procedures)
      1. 3,011 pts s/p total hip replacement randomized to enoxaparin 30mg SQ Q12h vs. warfarin (adjusted to INR 2.0-3.0) until discharge. Over 3mo f/u, no sig. diff. in incidence of DVT, PE, or death due to thromboembolism. Nonsig. higher incidence of major bleeding with enoxaparin (1.2% vs. 0.5%, p = 0.055) (J. Bone Joint Surg. Am 81:932, 1999--JW)
    2. Very-low-dose coumadin
  6. Hirudin analogues (hirudin, found in leaches, inactivates thrombin)
    1. Desirudin (recombinant hirudin)
    2. Bivalirudin (Hirulog), a synthetic peptide analogue of hirudin
  1. Sub-Q heparin vs. Sub-Q heparin plus SCD's--the latter is probably better
    1. 2551 pts randomized to SQ hep vs. both after cardiac surgery. PE occurred in 1.5% of those who got both; 4% of those who got hep (sig.) (Chest 109:82, 1996-JW)
    2. Sequential study of standard PE prophylaxis of SQ hep + thigh-high antiembolic stockings vs. same plus pneumatic compression boots; sig. lower rates of PE during time when the boots were in use (Neurol. 50:1683, 1998--JW)
  1. Low-molecular-weight Heparin vs.intermittent pneumatic compression boots
    1. 229 pts s/p total knee replacement randomized to Enoxaparin vs. intermittent compression foot-pump.  DVT on venography at 1wk was no different in 2 groups; 4% of IPC pts and 0% of enoxaparin pts had nonsig. lower incidence of prox. DVT and PE (J. Bone Joint Surg. Br. 84:344, 2002--JW)
  2. Ximelagatran
    1. 2301 pts undergoing total knee replacement randomized to ximelagatran 24mg BID or 36mg BID or warfarin (titrated to target INR 2.5) x 7-12d starting after surgery. Incidence of (death or any venous thromboembolism) was sig. lower in ximelagatran 36mg BID group than warfarin group (20% vs. 28%). No sig. diff. in any groups in incidence of proximal DVT or PE (NEJM 349:1703, 2003--JW)

IV. Prophylaxis in pregnant women

  1. For women with a h/o prior DVT or PE, risk in pregnancy is substantial (unclear just how substantial as of 2001); for pts with preg-ass'd DVT; recurrence rate in future pregnancies is 5-15%
  2. Risk factors = same as for non-pregnant pts, PLUS age > 35yo and multiparity
  3. Usually occurs 3rd trimester or postpartum; most PE's are postpartum
  4. In an observational study of 95 women with h/o prior LE DVT or PE (but no detectable hypercoagulable state, s.g. protein C or S deviciency or factor V Leiden mutation), a protocol of no anticoagulants during pregnany but SQ heparin (5kU-7.5kU SQ BID from delivery to d/c then adjusted-dose Coumadin for INR 2.0-3.0 for 4-6wks postpartum) was ass'd with 2 cases of preterm DVT, 1 of preterm PE, and 3 of postpartum DVT (NEJM 343:1439, 2000--AFP)
  5. Note: Spinal or epidural anesthesia probably safe in pts on low-dose SQ hep