A Broad Overview of Heparin and Low Molecular Weight Heparins

December 28, 2020

A Broad Overview of Heparin and Low Molecular Weight Heparins

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First available 1936
Mechanism of Action:  derived from bovine lung or porcine intestinal mucosa. Heparin binds to Antithrombin III and results in an inactivation of clotting factors IXa, Xa, XIIa and Thrombin (IIa).  By inactivating thrombin, it inhibits the thrombin induced factors V and VIII. Not only does Heparin prevent the growth and propagation of the formed thrombus, but it also allows the patient’s own thrombolytic system to degrade the clot.  Heparin may also have a direct effect on thrombolysis.
Dosage: each hospital develops its own nomograms that are specific for the reagent and instrument used to validate that nomogram. Is administered IV or SC.
Adverse effects: bleeding is the primary adverse effect. Watch for nosebleeds, hematuria, or tarry stools.
Minimal renal elimination, can be used for renal insufficiency or renal failure.
HIT:  Most common cause of DRUG INDUCED neutropenia. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin (ie, unfractionated heparin, low molecular weight [LMW] heparin) that occurs in up to 5 percent of patients exposed, regardless of the dose, schedule, or route of administration. More common with heparin.
Reversal: Protamine sulfate 1% solution will neutralize heparin.  Each mg of protamine neutralizes about 100 USP heparin units. Works in 5 minutes and is active for 2 hours. Should give via slow IV infusion over 10 minutes. Heparin also has a very short half-life of 60-90 minutes.
Contraindications: Use caution with elderly women; they are twice as likely to experience major bleeding than men. 
Severe uncontrolled hypertension is a contraindication.
Pregnancy category-C
Drug interactions: interactions do occur with NSAIDS, digitalis etc.  Since tight monitoring is required, dosage adjustments are easily made.
Drug monitoring: most common: APTT (Activated Partial Thromboplastin Time), is widely used, quickly done and reproducible. Do APTT six hour after bolus dose, or after any dosage change then every 6 hours until a therapeutic APTT is reached. Then evaluate every 24 hours. APTT= normal range is 25-35 seconds.  Ranges vary from lab to lab. Heparin induced APTT is 1.5 to 2.5 times normal.
Enoxaparin (Lovenox®)        
approved 1993
injection 30mg/0.3ml, 40/0.4ml, 60/0.6ml, 80/0.8ml, 100/1ml, 120/0.8ml, 150/ml & 300mg/3ml
Mechanism: inhibits factor IIa and to a much greater extent Xa.
DVT surgical prophylaxis: (dose dependent on surgical site)
DVT treatment with or without PE:
Outpatient treatment: patients with acute DVT without PE who can be treated at home. Typical outpatient dose: is 1mg/kg subcutaneously every 12 hours.
Adverse effects: minor bleeding, gingival bleeding, watch for GI or urogenital bleeding
Reversal: Protamine: give 1mg for every 1mg of enoxaparin. Protamine neutralizes only 60-75% of antithrombotic activity.  Not recommended if LMWH was given more than 12 hours earlier.
Pregnancy category B.  LMW does not cross placenta.  Appears to be safe to use during pregnancy. Good alternative to heparin when long term anticoagulation is necessary.
Caution with NSAIDS, they can increase bleeding.
Drug monitoring: because of predictable responses, routine monitoring of APTT is not necessary.  Have baseline PT, CBC, Creatinine then periodic monitoring of platelets and fecal occult blood.
Patient education: (enoxaparin)

  • Contact practitioner if bleeding, bruising, dizziness itching, rash or fever occurs.
  • Injections are given around the navel, upper thigh, or buttocks. Change site daily
  • Inject under skin not into muscle
  • If excessive bruising occurs at injection site it may be lessened by an ice cube massage on the site prior to injection.

NOTE:  other low molecular weight heparins are available, but enoxaparin (Lovenox®) is the most commonly used. Here are the others:

  • Dalteparin (Fragmin®)             
  • Tinzaparin (Innohep®)
  • Fondaparinux (Arixtra®)
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