heparin

Absorption: Erratically absorbed following SUBQ or IM administration. IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Probably removed by the reticuloendothelial system (lymph nodes, spleen).

Half-Life: 1–2 hr (↑ with increasing dose); affected by obesity, renal and hepatic function, malignancy, presence of PE, and infections.

Time/Action Profile ⬆ ⬇

(anticoagulant effect)

ROUTE	ONSET	PEAK	DURATION
SUBQ	20–60 min	2 hr	8–12 hr
IV	immediate	5–10 min	2–6 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Uncontrolled bleeding;
History of heparin-induced thrombocytopenia (HIT);
Severe thrombocytopenia;
Pedi: Avoid use of products containing benzyl alcohol in premature infants.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment;
Retinopathy (hypertensive or diabetic);
Ulcer disease;
Spinal cord or brain injury;
History of congenital or acquired bleeding disorder;
Malignancy;
Diabetes mellitus, chronic renal failure, metabolic acidosis, increased serum potassium, or concurrent use of potassium-sparing drugs (↑ risk of hyperkalemia);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; avoid use of products containing benzyl alcohol;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant; avoid use of products containing benzyl alcohol;
Geri: Women >60 yr have risk of bleeding.

Severe uncontrolled hypertension;
Bacterial endocarditis, bleeding disorders;
GI bleeding/ulceration/pathology;
Hemorrhagic stroke;
History of thrombocytopenia related to heparin;
Recent CNS or ophthalmologic surgery;
Active GI bleeding/ulceration.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia (long-term use), rash, urticaria

F and E: hyperkalemia

GI: ↑liver enzymes

Hemat: anemia, BLEEDING, HIT (WITH OR WITHOUT THROMBOSIS)

Local: pain at injection site

MS: osteoporosis (long-term use)

Misc: fever, hypersensitivity reactions

Interactions ⬆ ⬇

Heparin is frequently used concurrently or sequentially with other agents affecting coagulation. The risk of potentially serious interactions is greatest with full anticoagulation.

Drug-drug:

Risk of bleeding may be ↑ by concurrent use of drugs that affect platelet function, including aspirin, NSAIDs, clopidogrel, dipyridamole, some penicillins, eptifibatide, tirofiban, and dextran.
Risk of bleeding may be ↑ by concurrent use of drugs that cause hypoprothrombinemia, including quinidine, cefotetan, and valproic acid.
Concurrent use of thrombolytics↑ risk of bleeding.
Heparins affect the prothrombin time used in assessing the response to warfarin.
Digoxin, tetracyclines, nicotine, and antihistamines may ↓ anticoagulant effect of heparin.

Drug-Natural Products:

↑risk of bleeding with arnica, anise, chamomile, clove, dong quai, fever few, garlic, ginger, and Panax ginseng.

Route/Dosage ⬆ ⬇

Therapeutic Anticoagulation

IV (Adults ): Intermittent bolus: 10,000 units, followed by 5000–10,000 units every 4–6 hr. Continuous infusion: 5000 units (35–70 units/kg), followed by 20,000–40,000 units infused over 24 hr (approx. 1000 units/hr or 15–18 units/kg/hr).
IV (Children >1 yr): Intermittent bolus: 50–100 units/kg, followed by 50–100 units/kg every 4 hr. Continuous infusion: Loading dose 75 units/kg, followed by 20 units/kg/hr, adjust to maintain activated partial thromboplastin time (aPTT) of 60–85 sec.
IV (Neonates and Infants <1 yr): Continuous infusion: Loading dose 75 units/kg, followed by 28 units/kg/hr, adjust to maintain aPTT of 60–85 sec.
SC (Adults ): 5000 units IV, followed by initial SUBQ dose of 10,000–20,000 units, then 8000–10,000 units every 8 hr or 15,000–20,000 units every 12 hr.

Prophylaxis of Thromboembolism

SC (Adults ): 5000 units every 8–12 hr (may be started 2 hr prior to surgery).

Cardiovascular Surgery

IV (Adults ): At least 150 units/kg (300 units/kg if procedure <60 min; 400 units/kg if >60 min).
(Neonates , Infants, and Children): 100–150 units/kg via an artery prior to cardiac catheterization.

Line Flushing

IV (Adults and Children ): 10–100 units/mL (10 units/mL for infants <10 kg, 100 units/mL for all others) solution to fill heparin lock set to needle hub; replace after each use.

Total Parenteral Nutrition

IV (Adults and Children ): 0.5–1 units/mL (final solution concentration) to maintain line patency.

Arterial Line Patency

(Neonates ): 0.5–2 units/mL.

Availability ⬆ ⬇

(Generic available)

Premixed infusion: 1000 units/500 mL; 2000 units/1000 mL; 12,500 units/250 mL; 25,000 units in 250 and 500 mL
Solution for injection: 10 units/mL; 100 units/mL; 1000 units/mL; 5000 units/mL; 7500 units/mL; 10,000 units/mL; 20,000 units/mL; 40,000 units/mL

Assessment ⬆ ⬇

Assess for signs of bleeding and hemorrhage (bleeding gums; nosebleed; unusual bruising; black, tarry stools; hematuria; fall in hematocrit or BP; guaiac-positive stools). Notify health care professional if these occur.
- Assess patient for evidence of additional or increased thrombosis. Symptoms will depend on area of involvement.
- Monitor patient for hypersensitivity reactions (chills, fever, urticaria).
SC: Observe injection sites for hematomas, ecchymosis, or inflammation.

Lab Test Considerations:

Monitor aPTT and hematocrit prior to and periodically during therapy. When intermittent IV therapy is used, draw aPTT levels 30 min before each dose during initial therapy and then periodically. During continuous administration, monitor aPTT levels every 4 hr during early therapy. For SUBQ therapy, draw blood 4–6 hr after injection.
- Monitor platelet count every 2–3 days during therapy. May cause mild thrombocytopenia, which appears on 4th day and resolves despite continued heparin therapy. HIT, a more severe form that necessitates discontinuing medication, may develop on 8th day of therapy; may reduce platelet count to as low as 5000/mm³ and lead to ↑ resistance to heparin therapy. HIT may progress to development of venous and arterial thrombosis and may occur up to several wk after discontinuation. Patients who have received a previous course of heparin may be at higher risk for severe thrombocytopenia for several mo after the initial course.
- May cause hyperkalemia and ↑ AST and ALT levels.

Toxicity and Overdose:

Protamine sulfate is the antidote. Due to short half-life, overdose can often be treated by withdrawing the drug.

Implementation ⬆ ⬇

Fatal hemorrhages have occurred in pediatric patients due to errors in which heparin sodium injection vials were confused with heparin flush vials. Carefully examine all heparin sodium injection vials to confirm the correct vial choice prior to administration. Have second practitioner independently check original order, dose calculation, and infusion pump settings. Unintended concomitant use of two heparin products (unfractionated heparin and low-molecular-weight heparins) has resulted in serious harm or death. Review patients' recent (emergency department, operating room) and current medication administration records before administering any heparin or LMWH product.
Do not confuse heparin with Hespan. Do not confuse vials of heparin with vials of insulin.
Inform all personnel caring for patient of anticoagulant therapy. Venipunctures and injection sites require application of pressure to prevent bleeding or hematoma formation. Avoid IM injections of other medications; hematomas may develop.
- In patients requiring long-term anticoagulation, oral anticoagulant therapy should be instituted 4–5 days prior to discontinuing heparin therapy.
- Solution is colorless to slightly yellow.
SC: Administer deep into SUBQ tissue. Alternate injection sites between arm and the left and right abdominal wall above the iliac crest. Inject entire length of needle at a 45°- or 90°-angle into a skin fold held between thumb and forefinger; hold skin fold throughout injection. Do not aspirate or massage. Rotate sites frequently. Do not administer IM because of danger of hematoma formation. Solution should be clear; do not inject solution containing particulate matter.

IV Administration:

Diluent: Administer loading dose undiluted.Varies depending upon vial used.
Rate: Administer over at least 1 min. Loading dose given before continuous infusion.
Continuous Infusion: Diluent: Dilute 25,000 units of heparin in 250–500 mL of 0.9% NaCl or D5W. Premixed infusions are already diluted and ready to use. Admixed solutions stable for 24 hr at room temperature or if refrigerated. Premixed infusion stable for 30 days once overwrap removed.Concentration: 50–100 units/mL.
Rate: See Route/Dosage section. Adjust to maintain therapeutic aPTT. Use an infusion pump to ensure accuracy.
Flush: To prevent clot formation in intermittent infusion (heparin lock) sets, inject dilute heparin solution of 10–100 units/0.5–1 mL after each medication injection or every 8–12 hr. To prevent incompatibility of heparin with medication, flush lock set with sterile water or 0.9% NaCl for injection before and after medication is administered.

Patient/Family Teaching ⬆ ⬇

Explain purpose of heparin to patient.
Advise patient to report any symptoms of unusual bleeding or bruising to health care professional immediately.
- Instruct patient not to take medications containing aspirin or NSAIDs while on heparin therapy.
Caution patient to avoid IM injections and activities leading to injury and to use a soft toothbrush and electric razor during heparin therapy.
- Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
- Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇