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Heparin (Unfractionated)

Classification

Anticoagulant

Indications

CCP: Venous thromboembolism

CCP: Pulmonary embolism

CCP: Thromboembolic complications associated with atrial fibrillation.

CCP: Extracorporeal circulation

CCP: STEMI/NSTEMI

Contraindications

Hypersensitivity
Severe thrombocytopenia
History of heparin-induced thrombocytopenia
History of heparin-induced thrombocytopenia with thrombosis
Uncontrolled active bleeding
Not for use when appropriate blood coagulation tests cannot be obtained at appropriate intervals.
Some products contain benzyl alcohol as a preservative; their use in neonates, infants, or pregnant or breastfeeding women is contraindicated by some manufacturers.

Adult dosages

CCP: Thromboembolism

Loading dose: 80 u/kg/dose IV to a max of 5000 units
Maintenance: 12-18 u/kg/hour IV infusion to a max of 1000 u/hr

CCP: STEMI/NSTEMI

Loading dose: 60 u/kg IV to a max of 5000 units
Maintenance: 12 u/kg/hour IV infusion to a max of 1000 u/hr

CCP: Pulmonary embolism

Loading dose: 80u/kg IV or 5000 IV unit bolus
Maintenance: 18 u/kg/hr IV infusion

Pediatric Considerations And Dosing

CCP: Thrombosis

Infants
- Loading dose: 75 u/kg IV over 10 minutes
- Maintenance: 28 u/kg/hr IV infusion to maintain an aPTT or anti-Xa range of 0.35-0.7 u/ml
Children and Adolescents
- Loading dose: 75 u/kg IV over 10 minutes
- Maintenance: 20 u/kg/hr IV infusion to maintain an aPTT or anti-Xa range of 0.35-0.7 u/ml

CCP: ECMO

Loading dose: 100 u/kg IV prior to cannulation
Maintenance: Continuous IV heparin infusion to maintain the activated clotting time (ACT) between 180 and 220 seconds. ACT should be checked hourly while patient is on ECMO, additional monitoring targets for heparin therapy are prolongation of the PTT to 1.5 to 2.5 times the control value or an anti-Xa level of 0.3 to 0.7 units/ml.

Mechanism Of Action

Heparin potentiates the action of antithrombin III and thereby inactivates thrombin (as well as other coagulation factors IXa, Xa, XIa, XIIa, and plasmin). This inactivation then prevents the conversion of fibrinogen to fibrin. Heparin also stimulates the release of lipoprotein lipase (lipoprotein lipase hydrolyzes triglycerides to glycerol and free fatty acids).

Pharmacokinetics

Onset: IV immediate, SC 20-30 minutes

Half-life: 1.5 hours

Adverse Effects

Monitor for hyperkalemia; can cause hyperkalemia by suppressing aldosterone production.
Osteoporosis: May occur with prolonged use (>6 months) due to a reduction in bone mineral density.
Hemorrhage, which is not limited but may include, adrenal hemorrhage, ovarian hemorrhage, retroperitoneal hemorrhage.
Severe thrombocytopenia
HIT including delayed onset.
HITT including delayed onset.
Anaphylactoid reactions
Injection site necrosis
Neonatal gasping syndrome (benzyl alcohol-containing forms)
Fever
Rigors
Elevated ALT or AST

Overdose

Discontinue the Heparin infusion.
Administer Protamine Sulfate if necessary.

Warning And Precautions

Use with caution in patients with an increased risk of bleeding, as fatal bleeding events may occur.
Dose requirements >35,000 units/24 hours to maintain a therapeutic aPTT may occur in patients with antithrombin deficiency, increased heparin clearance, elevations in heparin-binding proteins, and elevations in factor VIII and/or fibrinogen.
Monitor for hyperkalemia; can cause hyperkalemia by suppressing aldosterone production.
Heparin-induced thrombocytopenia (HIT), a serious antibody-mediated reaction resulting from irreversible aggregation of platelets, may occur.
Use with caution in patients >60 years of age, particularly women; older adults can be more sensitive to heparin and a higher incidence of bleeding has been reported.
Confirm the concentration of all heparin injection vials prior to administration; do not use heparin injection as a "catheter lock flush" as the injection is supplied in various concentrations including highly concentrated strengths.

Drug Interactions

Defibrotide
Mifepristone
Oritavacin
Anagrelide
Argatroban
Betrixaban
Cilostazol
Diflunisal
Edoxaban
Fondaparinux
Ibritumomab tiuxetan
Omacetaxine mepesuccinate
Rivaroxaban
Vorapaxar