II. Indications

III. Contraindications (Indications for standard Heparin)

  1. Previous Deep Vein Thrombosis history
    1. Ipsilateral DVT
    2. Two or more DVTs
    3. Any Venous Thromboembolism
  2. High risk lesion (e.g. Iliofemoral DVT)
  3. Pregnancy
  4. Renal Insufficiency (Creatinine Clearance <30 due to risk of dose stacking and bleeding risk)
  5. Morbidly obese patients (consider Unfractionated Heparin where BMI>40-45 kg/m2)
  6. Hepatic Insufficiency
  7. Active bleeding
  8. Surgery in prior 5-7 days (However see below)
  9. Hypercoagulable state
    1. Protein C Deficiency
    2. Protein S Deficiency
    3. Antithrombin III deficiency
  10. Inability to undergo outpatient treatment
  11. Noncompliance
  12. Thrombocytopenia
  13. Coagulopathy
  14. Active Peptic Ulcer Disease

IV. Efficacy: Unstable Angina and Myocardial Infarction

  1. Significantly better outcomes than standard Heparin
    1. Randomized trial (n=3171)
    2. Lower endpoint (death, Myocardial Infarction, Angina)
      1. 14 days (16.6 vs 19.8%)
      2. 20 days (19.8 vs 23.3%)
    3. Fewer revascularization procedures (27 vs 32.2%)
  2. Reference
    1. Cohen (1997) N Engl J Med 337:447-52 [PubMed]

VI. Advantages: LMWH over Unfractionated Heparin

  1. Rarely causes Heparin Induced Thrombocytopenia
  2. Does not cause paradoxical thrombotic events
  3. Results in fewer bleeding complications
  4. References
    1. Warkentin (1995) N Engl J Med 332:1330-5 [PubMed]
    2. (1995) Arch Intern Med 155:601 [PubMed]

VII. Dosing

  1. General
    1. Prophylaxis: Consider increasing the dose by 25% when BMI >40 kg/m2
    2. Treatment: Dose should be based on total body weight (even in obese patients)
    3. Exception: Fragmin has a maximum dose (unlike other LMWH agents)
    4. See specific preparation (e.g. Enoxaparin or Lovenox) for adjustments for Renal Function and Obesity
  2. Deep Vein Thrombosis Treatment
    1. Enoxaparin (Lovenox)
      1. Twice daily dosing: 1 mg/kg SQ twice daily
      2. Avoid once daily dosing of 1.5 mg/kg SQ daily (less effective, esp. in obese patients, and not for home)
      3. Available in 30 mg vials
    2. Tinzaparin (Innohep)
      1. Dose: 175 anti-Xa IU per kg daily
      2. Dose (ml): (weight in kg) x 0.00875 ml/kg daily
  3. Deep Vein Thrombosis Prophylaxis
    1. Ardeparin (Normiflo)
      1. Initial: 50 U/kg SQ following surgery
      2. Later: bid for 14 days or until ambulatory
    2. Dalteparin (Fragmin)
      1. Low risk
        1. Initial: 2500 IU SQ 1-2 hours before surgery
        2. Later: 2500 IU qd for 5-10 days
      2. High risk
        1. Initial: 5000 IU SQ the evening before surgery
        2. Later: 5000 IU qd for 5-10 days
    3. Danaparoid (Orgaran)
      1. Initial: 750 U SQ 1-4 hours before surgery
      2. Later: then 750 U SQ q12h for 7-10 days
    4. Enoxaparin (Lovenox)
      1. Initial: 30 mg SQ q12h OR 40 mg daily for 7-10 days
      2. Increase to 40 mg twice daily for obese patients
    5. Tinzaparin (Innohep)
      1. Innohep 3500 IU SQ daily

VIII. Precautions

  1. Severe Renal Insufficiency
    1. Unpredictable dose response to LMWH
    2. CrCl <30 ml/min: See specific preparation regarding dosing (e.g. Enoxaparin or Lovenox)
    3. CrCl <15 ml/min: Use Unfractionated Heparin
  2. Obesity (BMI>40)
    1. Dosing frequency may need adjustment
    2. Lovenox has been studied at 1 mg/kg up to 190 kg
      1. For weights above this, follow anti-Xa levels
  3. Reversal
    1. Protamine
      1. Less responsive to Protamine compared with Heparin

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Ontology: Heparin, Low-Molecular-Weight (C0019139)

Definition (NCI) Substances comprised of fragmented heparin molecules derived from unfractionated heparin that bind to antithrombin III with a molecular weight ranging from 1000 to 10,000 daltons, which causes changes in property from unfractionated heparin, including decreased protein binding, enhanced bioavailability, decreased platelet interaction, and decreased binding to thrombin.
Definition (MSH) Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism.
Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH D006495
SnomedCT 373294004, 87233003
LNC LP16001-7, LP172751-2, MTHU014939
English Heparin, Low Molecular Weight, Low Molecular Weight Heparin, LMWH, Low-Molecular-Weight Heparin, Low Mol Wt Heparin (Obsolete), LOW MOL WEIGHT HEPARIN, HEPARIN LOW MOL WEIGHT, HEPARIN LMW, LMW HEPARIN, Heparin, Low-Molecular-Weight, Heparin, Low-Molecular-Weight [Chemical/Ingredient], heparin low molecular weight, low molecular heparin weight, low heparin molecular weight, low molecular weight heparins, anti-xa, lmwh, low molecular weight heparin, anti xa, low-molecular-weight heparin, heparins low molecular weight, Heparin.low molecular weight, Low molecular weight heparin, Low molecular weight heparins, Low molecular weight heparin (product), Low molecular weight heparin (substance)
Swedish Heparin, lågmolekylärt
Czech heparin nízkomolekulární
Finnish Pienimolekyylinen hepariini
Russian NIZKOMOLEKULIARNYI GEPARIN, GEPARIN NIZKOMOLEKULIARNYI, ГЕПАРИН НИЗКОМОЛЕКУЛЯРНЫЙ, НИЗКОМОЛЕКУЛЯРНЫЙ ГЕПАРИН
Japanese 低分子量ヘパリン, ヘパリン-低分子量
Polish Heparyna LMW, Heparyna o niskim ciężarze cząsteczkowym
Croatian NISKOMOLEKULARNI HEPARIN, HEPARIN, NISKOMOLEKULARNI
Portuguese HBPM, LMWH, Heparina de Baixo Peso Molecular
Spanish heparina de bajo peso molecular (producto), heparina de bajo peso molecular (sustancia), heparina de bajo peso molecular, HBPM, Heparina de Bajo-Peso-Molecular
French Héparine bas poids moléculaire, Héparine faible masse moléculaire
German Heparin, niedrigmolekulares, LMWH, Niedrigmolekulares Heparin
Italian Eparina a basso peso molecolare

Ontology: Orgaran (C0163842)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C035838
English Orgaran

Ontology: Dalteparin (C0206461)

Definition (NCI_NCI-GLOSS) A drug used to prevent blood clots from forming or to treat blood clots that have formed in patients with cancer or other conditions. Dalteparin is a type of anticoagulant.
Definition (NCI) A low molecular weight, synthetic heparin. As an anticoagulant/antithrombotic agent, dalteparin binds to antithrombin and enhances the inhibition of Factor Xa. Compared to unfractionated heparins, the use of dalteparin is associated with lower incidences of osteoporosis and heparin-induced thrombocytopenia. (NCI04)
Definition (MSH) A low-molecular-weight fragment of heparin, prepared by nitrous acid depolymerization of porcine mucosal heparin. The mean molecular weight is 4000-6000 daltons. It is used therapeutically as an antithrombotic agent. (From Merck Index, 11th ed)
Definition (PDQ) A low molecular weight, synthetic heparin. As an anticoagulant/antithrombotic agent, dalteparin binds to antithrombin and enhances the inhibition of Factor Xa. Compared to unfractionated heparins, the use of dalteparin is associated with lower incidences of osteoporosis and heparin-induced thrombocytopenia. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43290&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43290&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1453" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH D017985
SnomedCT 108986009, 372563008
Swedish Dalteparin
Czech dalteparin, tedelparin
Finnish Tedelpariini
Russian DALTEPARIN, TEDELPARIN, ТЕДЕЛПАРИН, ДАЛТЕПАРИН
Japanese フラグミン, テデルパリン, ダルテパリンナトリウム, ダルテパリン
English Dalteparin [Chemical/Ingredient], dalteparin, DALTEPARIN, Dalteparin (product), Dalteparin (substance), DAL, Dalteparin, Tedelparin
Polish Dalteparyna, Tedelparyna
Spanish dalteparina (producto), dalteparina (sustancia), dalteparina, Dalteparina, Tedelparina
German Dalteparin, Tedelparin
Portuguese Dalteparina, Tedelparina
Italian Tedelparina, Dalteparina
French Tedelparine, Daltéparine

Ontology: tinzaparin (C0216278)

Definition (NCI_NCI-GLOSS) A drug that is used with another drug, warfarin, to treat blood clots that form deep in the veins and to prevent new blood clots from forming. It is a type of anticoagulant.
Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH C081247
SnomedCT 350469004, 412608008
English tinzaparin, tinzaparin [Chemical/Ingredient], B01AB10, TINZAPARIN, Tinzaparin, Tinzaparin (product), Tinzaparin (substance)
Spanish tinzaparina (producto), tinzaparina, tinzaparina (sustancia)

Ontology: danaparoid (C0259507)

Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH C035838
SnomedCT 108992003, 372564002
English danaparoid, DANAPAROID, Danaparoid (product), Danaparoid (substance), Danaparoid
Spanish danaparoide (producto), danaparoide (sustancia), danaparoide

Ontology: Normiflo (C0297267)

Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH C093450
English Normiflo

Ontology: ardeparin (C0297269)

Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH C093450
SnomedCT 108989002, 373731006
English ARDEPARIN, ardeparin, ardeparin [Chemical/Ingredient], Ardeparin, Ardeparin (product), Ardeparin (substance)
Spanish ardeparina (producto), ardeparina (sustancia), ardeparina

Ontology: Innohep (C0591649)

Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH C081247
English Innohep, innohep, Bristol-Myers Squibb brand of tinzaparin sodium, Leo brand of tinzaparin sodium

Ontology: Fragmin (C0917726)

Concepts Pharmacologic Substance (T121) , Carbohydrate (T118)
MSH D017985
English Fragmine, Pfizer Brand of Dalteparin Sodium, fragmin, Fragmin
Czech Fragmin
French Fragmin