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- See:
      - DVT risk reduction
      - DVT risk reduction - THR
      - Low Molecular Wt Heparins:

- Discussion:
    - mechanism of action: (see coag pathway);
         - binds anti-thrombin III, blocks conversion of Prothrombin to Thrombin, also hits Xa, IXa, and XIa;
         - will produce immediate prolongation of the aPTT, and to a lesser extent, the PT;
    - indications:
         - for treatment of DVT & PE (see hypercoagulable states);

- Dosage:
    - adult prophylaxis:
         - 3000-15,000 units SQ q8-12hr, so that PTT = 1.5 times the control PTT;
    - thrombosis / PE:
         - loading dose: 50-100 units/kg IV (usual 5,000-10,000 units bolus injection);
         - then 10-20 units/kg IV q1hr,  (usual 1000 units/hr) and titrate, w/ PTT adjusted intially q4-6hr,
         - then after PTT is stable check each day, until PTT = 1.5-2.0 x normal, after this check PTT qd; t/2= 1.5-3 hrs;
     - peds: infants:
         - load 50 Units/kg IV bolus then 10-20 Units/kg/hr IV by continuous infusion;
         - children: load: 50 Units/kg IV then 15-25 Units/kg continuous infusion of 100 Units/kg/dose q4hr IV intermittent bolus;
     - method of delivery:
         - for delivery, use an infusion pump, w/ maintenance dose;
         - supplied: solutions of 1000-4000 USP units/ml;
         - supplied: 100, 1000, 5000, 10,000, 20,000, 40,000 U/ml;
         - 25,000units/500 ml D5W to run at 20 ml/hr = 1000 units/hr;
         - do not put large doses of herparin in small volume IV bags as "run away" IV's filled w/ heparin can result in Over-Dose;
         - concentration of Heparin must not be > 20,000 units/lit IV fluid;

- Complications:

    - acute bleeding:
         - by simply d/c'ing heparin (t/2=1.5 hrs), will normalize aPTT;
         - serious heparin induced bleeding is treated w/ protamine sulfate:
         - 1mg protamine sulfate for each 100 units of heparin;
    - heparin induced thrombocytopenia
    - osteoporosis:
         - prolonged administration of heparin may lead to osteoporosis;
    - references:
         - Destructive monarticular arthritis secondary to anticoagulant therapy.

Review Article: Drug Therapy -- Heparin

Special Article: Reduction in Fatal Pulmonary Embolism and Venous Thrombosis by Perioperative Administration of Subcutaneous Heparin: Overview of Results of Randomized Trials in General, Orthopedic, and Urologic Surgery.

Current Concepts Review.  Prophylaxis of Venous Thromboembolic Disease Following Hip and Knee Surgery.

Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40.

Prevention of venous thrombosis after total knee arthroplasty. Comparison of antithrombin III and low-dose heparin with dextran.

The effect of intravenous fixed-dose heparin during total hip arthroplasty on the incidence of deep-vein thrombosis. A randomized, double-blind trial in patients operated on with epidural anesthesia and controlled hypotension.

Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.

Arterial thromboembolism in patients receiving systemic heparin therapy: a complication associated with heparin-induced thrombocytopenia.

Complications of arterial puncture in anticoagulated patients.

Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study.

Intraoperative adjusted-dose heparin thromboembolic prophylaxis in primary total hip arthroplasty.

Intraoperative heparin thromboembolic prophylaxis in primary total hip arthroplasty. A prospective, randomized, controlled, clinical trial.

Reactivation of unstable angina after the discontinuation of heparin

Adjusted Versus Fixed-Dose Subcutaneous Heparin in the Prevention of Deep-Vein Thrombosis after Total Hip Replacement

Subcutaneous Low-Molecular-Weight Heparin Compared with Continuous Intravenous Heparin in the Treatment of Proximal-Vein Thrombosis.