Low Molecular Weight Heparins

Low molecular weight heparins are smaller pieces of the heparin molecule that inhibit clotting factor Xa more than factor IIa (thrombin). These drugs are given subcutaneously and can usually be administered in a weight-based dose without subsequent monitoring or dose-adjustment. At a higher dose these drugs are used to treat active thrombotic disease and at lower dose to prevent thrombosis. Three LMW-heparins are widely used in the United States and Canada. They are dalteparin, enoxaparin, and tinzaparin.

*For enoxaparin 1 mg = 100 antiXa units. Enoxaparin also is used at 40 mg q 24h for longer term outpatient proplylaxis in outpatients after hip or knee replacement.

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Use Of Low Molecular Weight Heparin To Treat Unstable Angina

LMW-heparins have proven to be at least as effective as intravenous unfractionated heparin in the treatment of unstable angina. Cost-analysis of LMW-heparin treatment of unstable angina indicate that when total costs are considered, LMW-heparin incurs no more expense than unfractionated-heparin. Dalteparin and enoxaparin are both approved for treatment of unstable angina. Enoxaparin or dalteparin can be given safely to any patient who is a candidate for unfractionated heparin. The major contraindications are active internal bleeding and heparin-induced thrombocytopenia (HIT).

Guidelines for Enoxaparin Treatment of Unstable Angina

• Obtain baseline ECG, cardiac enzymes, troponin, APTT, PT, and CBC
• Determine need for thrombolytic therapy
• Start aspirin, ß-adrenergic blocker and nitrates
• Check for contraindications to LMW-heparin
• Start enoxaparin* or dalteparin* subcutaneously q 12 hr without monitoring or dose-adjustment
• Determine need for long-term anticoagulants (warfarin)

*Dalteparin: 120 anti-Xa U/kg subcutaneously q 12 hr. Enoxaparin 1 mg/kg subcutaneously q 12 hr

Thrombolytic Therapy and LMW-Heparins

LMW-heparin is used in place of unfractionated heparin in unstable angina (UA). If a patient with unstable angina requires thrombolytic therapy because of ST-segment elevation or new LBBB, follow these recommendations:

• TPA (Activase®, Retavase® or TNKase ): If the last LMW-heparin injection occurred within 6 hrs, the patient can be assumed to be anticoagulated and no concurrent heparin is necessary. If the last LMW-heparin injection occurred more than 6-8 hrs. previously, give concurrent IV unfractionated heparin with the TPA.
• Streptokinase- Hold the LMW-heparin during the SK infusion and give the next injection as scheduled after the APTT or TT has returned to less than 1½ times mean normal.
• Invasive Procedures and LMW-Heparins- If cardiac catheterization or coronary artery bypass surgery is to occur within 6 hrs. of a LMW-heparin dose, the patient can be assumed to be fully anticoagulated. If the procedure is to be done more than 6 hrs. after a LMW-heparin dose, IV unfractionated heparin can be given and followed with an activated clotting time (ACT). LMW-heparins have very little effect on the ACT.
• Reversing the effect of LMW-heparin- Although it is rarely necessary, LMW-heparin can be partially neutralized with protamine sulfate. This is rarely necessary. Please see the package insert or PDR for details.
  

Dalteparin has been studied in the treatment of deep venous thrombosis (DVT) and unstable angina (UA).

Treatment of DVT

Dalteparin Dose: 120 anti-Xa U/kg q 12 h

1. A Collaborative European Multicentre Study. Thromb Haemostasis 1991; 65:251-56

Dalteparin Dose: 200 anti-Xa U/kg q 24 h

1. Lindmarker P, Holmstrom M, Granqvist S, et al. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1994; 72:186-90
   
   
2. Fiessinger JN, Lopez-Fernandez M, Gatterer E, et al. Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76:195-9
   
   
3. Luomanmaki K, Granqvist S, Hallert C, et al. A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. J Int Med 1996; 240:85-92

Treatment of UA

Dose: 120 anti-Xa U/kg q 12 h

1. Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Lancet 1996;347:561-8

Tinzaparin has been studied in both DVT and PE. The drug is approved for treatment of DVT with or without PE. The effective treatment dose is 175 anti-Xa U/kg q24h.

1. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heaprin compared with continuous intravenous heparin in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992;326:975-82

2. Simonneau G, Sors B, Charbonnier Y, et al. A comparison of low-molecular-weight heparin with unfractionalted heparin for acute pulmonary embolism. N Engl J Med 1997;337:663-9

	Initial Assessment of Patient
	Evidence of DVT. Stool guaiac and weight in office	NO		F.U. Telephone call from office
	Call Case Manager. Send for duplex sonography	NEG		Symptomatic Rx
	Positive Sonogram
	Evaluate inpatient vs. outpatient criteria-	In-Pt. Criteria		Admit; initiate inpatient Care Path
	Eligible for outpt. Rx.
Day 1---------------	1. Pt. to lab in Wc from Ultrasound. 2. Call Case Mgr. with orders. 3. Patient Education. 4. Administer 1st doses of LMWH & Warfarin after normal lab results back.
Day 2---------------	RN Telephone Assessment
Day 3 --------------	PT/INR/Plt Ct. Warfarin Protocol RN Assessment