Heparin - Unfractionated Heparin

There is a 10-fold intersubject variability in response to a given dose of Heparin; hence with full-dose Heparin therapy its coagulation effect (APTT ratio) must be monitored at least daily and the dose adjusted to achieve the target therapeutic range, within which the risks of bleeding and thrombosis are each minimised

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• Naturally-occurring glycosaminoglycan (porcine or bovine)
• Used both in treatment and prevention of thrombosis
• Indirect thrombin inhibitors

Properties

• Action is quickly reversible with protamine and half life is 30-120 minutes.
• Molecular weight range of 5,000-35,000 daltons (mean 12-14,000)
• Binds to antithrombin and enhances inactivation of factor Xa and potentiates AT3
• Has a double action which makes its activity more unpredictable vates activated clotting factors (thrombin and factor Xa) by potentiating the effect of the endogenous coagulation inhibitor, antithrombin
• It therefore prolongs the activated partial thromboplastin time (APTT)
• Always look out for Heparin-induced thrombocytopenia, it does not usually develop until after 5-10 days

Indications

• Acute thrombosis needing close control e.g. additional bleeding risk
• Used in cardiopulmonary bypass/renal dialysis
• IV perioperatively e.g. carotid endarterectomy
• Acute coronary syndrome post thrombolysis
• VTE prophylaxis given subcutaneously (replaced by LMWH)
• Low dose to flush vascular catheters

Cautions

• Do not take blood for APTT from drip arm receiving UFH.
• Thrombocytopenia, haemophilias, liver failure, renal failure
• Systolic >200 mm Hg or diastolic >120 mm Hg
• Active peptic ulcer, oesophageal varices
• Aneurysm, proliferative retinopathy, recent organ biopsy
• Recent trauma or surgery to head, orbit, spine, recent stroke
• Confirmed intracranial or intraspinal bleed
• History of Heparin-induced thrombocytopenia or thrombosis

Monitoring

• The APTT is used and the target ratio is usually 1.5-2.5
• Plasma anti-Xa assays activity

Side effects

• Bleeding - take advice, give protamine, transfuse.
• Heparin induced thrombocytopenia: Seen in 5% which is more common the longer treatment duration. Stop all Heparins and seek haematology advice.
• Hyperkalaemia, Osteoporosis with long term use.

Dose (UFH)

• VTE prophylaxis: Medical patients: Heparin 5,000 s/c 8-12 hrly (nowadays largely replaced by LMWH).
• VTE prophylaxis: Surgical patients: Heparin 5000 units 2 h pre-op then 5000 U SC 8-12 h.
• Acute Thrombus e.g. DVT/PE: Heparin loading 5000 U (10 000 U if severe PE) and then 18 U/kg/h IV.
• Typical dose is 1000-2000 units/hour iv adjusted to APTT.
• Check APTT every 4-6 hours. Heparin is made up of 25,000 units Heparin in 50 ml of N-saline (1 ml = 500 u) and start at calculated dose per hour and adjust as per APTT.

  APTT	Heparin sodium 1000 U/ml
  >5.0	stop for 2 h; reduce by 0.5 ml/h (500 U) and recheck at 4 h
  4.1-5	stop for 1 h; reduce by 0.3 ml/h (300 U) and recheck at 4 h
  3.6-4	reduce by 0.2 ml/h (200 U)
  3.1-3.5	reduce by 0.1 ml/h (100 U)
  2.0-3.0	NO CHANGE
  1.5-1.9	increase by 0.1 ml/h (100 U)
  1.2-1.4	increase by 0.2 ml/h (200 U)
  <1.2	give 2500 U IV bolus; increase by 0.4 ml/h (400 U)