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low molecular weight (LMW) heparin

Made from unfractionated heparin using a variety of methods.* MW: 5 kD (vs heparin 15 kD) Indications: - treatment of venous thromboembolism - deep vein thrombosis - pulmonary embolism [8] - DVT prophylaxis - total knee arthroplasty* - total hip arthroplasty* - abdominal surgery - malignant neoplasm [8] - arterial thromboembolism - unstable angina - acute myocardial infarction - ST segment-elevated myocardial infarction - non-Q-wave myocardial infarction - patency of indwelling lines/devices - percutaneous coronary intervention [8] * patients who did not receive spinal anesthesia Advantages: 1) long 1/2 life 2) more predictable anticoagulant effect - less bleeding* - decreased recurrent thrombosis* 3) less thrombocytopenia* 4) no need to monitor aPTT 5) lower mortality* [3] * over heparin Disadvantages: - expensive Contraindications: 1) recent spinal or epidural anesthesia 2) morbid obesity 3) hypersensitivity to heparin or porcine proteins 4) history of heparin-induced thrombocytopenia 5) GI disease/bleed within 2 weeks 6) high-dose NSAID therapy 7) current CNS insult (stroke, spinal cord injury, neurosurgery) 8) renal failure, creatinine clearance < 20-30 mL/min [3] pregnancy-category B safety in lactation ? Dosage: 1) QD or BID weight-based dosing 2) overlap with warfarin therapy, discontinue when INR is therapeutic for 2 consecutive days 3) discontinue for 12 hours prior to surgery [6], including placement or removal of spinal catheter [7], longer for therapeutic doses of LMW heparin [7] 4) delay restarting LMW heparin for at least 4 hours after spinal catheter removal [7] 5) see individual LMW heparin Protocol: (prior to starting LMW heparin) 1) laboratory a) complete blood count (platelets) b) PT/aPTT 2) history of hemorrhage a) gastrointestinal bleeding b) hemorrhagic stroke Pharmacokinetics: 1) bioavailability is 90% following SC administration 2) different preparations have different activity & different 1/2life 3) elimination is prolonged with renal insufficiency [10,11] Monitor: 1) NOT necessary in non-pregnant patients 2) anti-factor Xa activity - check factor Xa activity 4 hours after LMW heparin dose in patients with chronic renal failure stage 5 [3] - MKSAP19 suggests adjusting dose according to product labeling rather than measuring factor Xa activity [3] 3) most LMW heparins do not prolong aPTT [4] Adverse effects: 1) major & minor bleeding 2) fever 3) pain 4) necrosis at the site of injection 5) elevation in serum transaminases 6) thrombocytopenia (less than heparin) 7) nausea 8) peripheral edema 9) confusion Overdose - treat with protamine sulfate Drug interactions: 1) high dose NSAIDs or glucocorticoids a) increases the risk of renal & GI-related toxicity b) should not be used concurrently with LMW heparin 2) in combination with spinal anesthesia associated with: a) spinal hematoma b) neurologic injury c) permanent paralysis Mechanism of action: 1) binds to antithrombin III (AT3) accelerating the rate AT3 neutralizes activated clotting factors 2) has higher anti factor Xa/anti factor IIa than does heparin 3) may diminish mortality in cancer patients, possibly via inhibition of angiogenesis [4] * see dalteparin for comparison of different LMW heparins.

Interactions

drug adverse effects of LMW heparin

Related

antithrombin-III (ATIII, heparin cofactor, SERPINC1, AT3, PRO0309)

Specific

ardeparin (Normiflo) dalteparin (Fragmin) enoxaparin (Lovenox) tinzaparin (Innohep)

General

heparin

Database Correlations

PUBCHEM cid=772

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022.
  4. Journal Watch 25(10):84, 2005 Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, Prandoni P, Bos MM, Richel DJ, van Tienhoven G, Buller HR. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005 Apr 1;23(10):2130-5. Epub 2005 Feb 7. PMID: 15699479 - Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005 Apr 1;23(10):2123-9. Epub 2005 Feb 7. PMID: 15699480
  5. UpToDate 14.1 http://www.utdol.com
  6. O'Donnell MJ, Kearon C, Johnson J, Robinson M, Zondag M, Turpie I, Turpie AG. Brief communication: Preoperative anticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin. Ann Intern Med. 2007 Feb 6;146(3):184-7. PMID: 17283349
  7. FDA MedWatch Low Molecular Weight Heparins: Drug Safety Communication - Recommendations to Decrease Risk of Spinal Column Bleeding and Paralysis. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm373918.htm
  8. Deprecated Reference
  9. Kalyani BS, Roberts CS. Low molecular weight heparin: current evidence for its application in orthopaedic surgery. Curr Vasc Pharmacol. 2011 Jan;9(1):19-23. PMID: 21044028
  10. Saltiel M. Dosing low molecular weight heparins in kidney disease. J Pharm Pract. 2010 Jun;23(3):205-9. Review. PMID: 21507815
  11. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013