Brand name: HepFlush
Drug class: Heparins
CAS number: 9041-08-1

Medically reviewed by Drugs.com on Feb 21, 2024. Written by ASHP.

Introduction

Anticoagulant; a heterogeneous group of anionic, sulfated glycosaminoglycans.

Unless otherwise specified in this monograph, the term “heparin” refers to “unfractionated heparin”, not low molecular weight heparin (LMWH) or both types of heparin.

Uses for Heparin

Treatment of Venous Thromboembolism

Treatment of DVT and PE.

Recommended by the American College of Chest Physicians (ACCP) as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT or PE.

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment. IV heparin also may be preferred over sub-Q therapies in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.

After full-dose heparin therapy, warfarin or an LMWH generally is administered as follow-up anticoagulant therapy for ≥3 months in adults with venous thromboembolism.

Thromboprophylaxis in General Surgery

Prophylaxis of postoperative DVT and PE in patients undergoing general (e.g., abdominal) surgery who are at risk of thromboembolism.

ACCP recommends pharmacologic (e.g., low-dose heparin) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding. In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.

If pharmacologic prophylaxis is indicated in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin is preferred.

ACCP states that the same recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that low-dose heparin may be considered in cardiac surgery patients with a complicated postoperative course.

Thromboprophylaxis in Neurosurgery

Has been used for prevention of venous thromboembolism in patients undergoing craniotomy^{† [off-label]}; however, benefits may be outweighed by possible increased risk of intracranial hemorrhage. ACCP states that the addition of low-dose heparin to a mechanical method of prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.

Also may be considered as a possible addition to mechanical prophylaxis in high-risk patients undergoing spinal surgery^{† [off-label]} (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.

Thromboprophylaxis in Thoracic Surgery

Prevention of postoperative DVT and PE in patients undergoing major thoracic surgery.

Pharmacologic thromboprophylaxis (e.g., low-dose heparin) recommended by ACCP in patients undergoing thoracic surgery who are at high risk of venous thromboembolism, provided risk of bleeding is low.

Thromboprophylaxis in Major Orthopedic Surgery

Has been used for prevention of DVT and PE in patients undergoing total hip-replacement surgery^{† [off-label]}, total knee-replacement surgery^{† [off-label]}, or hip-fracture surgery^{† [off-label]}.

ACCP recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.

Among several antithrombotic agents (e.g., LMWH, fondaparinux, low-dose heparin, warfarin, aspirin) recommended for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery, ACCP states LMWHs generally preferred; may consider alternative agents when an LMWH is not available or cannot be used.

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy and safety of the drugs in addition to other logistics and compliance issues.

Thromboprophylaxis in Selected Medical Conditions

Used for prevention of DVT and PE in acutely ill hospitalized medical patients and in those with medical conditions associated with a high risk of thromboembolism (e.g., cancer).

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.

ACCP recommends anticoagulant prophylaxis (e.g., low-dose heparin) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding. Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or hospital discharge.

Low-dose heparin also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.

Risk of venous thromboembolism is particularly high in patients with cancer. Use of low-dose heparin suggested by ACCP in cancer (solid tumors) outpatients who have additional risk factors for thromboembolism, provided risk of bleeding is low.

Thromboprophylaxis in Trauma

Low-dose heparin may be used for thromboprophylaxis in patients with major trauma^†. For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests the use of both a pharmacologic and mechanical method of prophylaxis, unless contraindications exist.

Thromboembolism During Pregnancy

Has been used for prevention and treatment of venous thromboembolism during pregnancy; however, an LMWH generally is recommended by ACCP because of a more favorable safety profile.

Complications of Pregnancy

Has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibodies (APLA) syndrome^†.

Also has been used with aspirin (often combined with immune globulin) for prevention of venous thromboembolism and early pregnancy loss in women who have undergone in vitro fertilization^†.

Venous Thromboembolism in Pediatric Patients

Has been used for treatment and secondary prevention of venous thromboembolism in neonates and children^†; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device) in such patients.

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.

In children with central venous catheters (or umbilical venous catheters) who experience venous thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation suggested prior to removal. If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.

Cardioversion of Atrial Fibrillation/Flutter

Has been used to reduce the risk of stroke and systemic embolism in patients undergoing electrical or pharmacologic cardioversion^† for atrial fibrillation or atrial flutter.

Therapeutic anticoagulation with heparin may be used in patients in whom prolonged anticoagulation (e.g., with warfarin for ≥3 weeks) prior to cardioversion is not necessary or not possible; in these situations, heparin or an LMWH generally is administered at the time of transesophageal echocardiograph (TEE) or at presentation (for those with atrial fibrillation ≤48 hours) just prior to cardioversion.

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of IV heparin or an LMWH prior to cardioversion, if possible; however, such anticoagulant therapy must not delay any emergency intervention.

Thromboembolism Associated with Prosthetic Heart Valves

Used during conversion to maintenance warfarin therapy to reduce the incidence of thromboembolism (e.g., stroke) in patients with prosthetic mechanical heart valves^†.

ACCP suggests bridging anticoagulation (administration of an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve until patient is stable on warfarin therapy.

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., for major surgery). ACC and AHA state that perioperative use of heparin should be considered for noncardiac surgery, invasive procedures, or dental procedures in patients with prosthetic heart valves who are at high risk for thrombosis without oral antithrombotic therapy (e.g., those with any mechanical mitral valve or a mechanical aortic valve with additional risk factors).

Used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves^†. (See Thromboembolism During Pregnancy under Dosage and Administration.)

Renal Vein Thrombosis

Renal vein thrombosis^† is the most common cause of spontaneous venous thromboembolism in neonates. Although use of anticoagulant therapy in patients with renal vein thrombosis is controversial, heparin is suggested by ACCP as a possible treatment option in selected neonates.

Arterial Thromboembolism

Used to reduce the extent of ischemic injury in patients with acute arterial emboli or thrombosis; however, ACCP states formal studies demonstrating improved outcomes have not been conducted.

In patients with limb ischemia secondary to arterial emboli or thrombosis, immediate systemic anticoagulation with heparin to prevent thrombotic propagation is suggested by ACCP.

Prophylaxis during cardiac catheterization via an artery in neonates and children. If femoral artery thrombosis occurs following cardiac catheterization, therapeutic-dose IV heparin is recommended, followed by subsequent conversion to an LMWH or continued treatment with heparin to complete 5–7 days of therapeutic anticoagulation.

Thromboembolism Associated with Cardiac and Arterial Vascular Surgery

Prevention of activation of the coagulation mechanism during arterial and cardiac surgery.

A nonheparin anticoagulant (e.g., bivalirudin) may be used in place of heparin in patients with acute heparin-induced thrombocytopenia (HIT) or subacute HIT (platelets have recovered, but HIT antibodies still present) who require urgent cardiac surgery. Because HIT antibodies are transient, ACCP states that short-term use of heparin may be appropriate in patients with a remote (>3 months) history of HIT and no detectable antibodies who require cardiac surgery.

Disseminated Intravascular Coagulation

Treatment of acute and chronic consumptive coagulopathies, including disseminated intravascular coagulation.

Thrombosis Associated with Indwelling Venous or Arterial Devices

Maintenance of patency of indwelling peripheral or central venipuncture devices designed for intermittent injections and/or blood sampling.

ACCP suggests use of heparin flushes as an option for primary thromboprophylaxis of central venous access devices in children.

In neonates and children with peripheral arterial catheters, ACCP recommends continuous IV infusion of heparin (in low concentrations) via the catheter for prophylaxis. Also may consider use of heparin for treatment if symptomatic catheter-related thromboembolism occurs.

In neonates with umbilical arterial catheters, ACCP also suggests thromboprophylaxis with low-dose heparin via the catheter to maintain patency.

ST-Segment-Elevation MI (STEMI)

Used in combination with antiplatelet agents (e.g., aspirin) during and after successful coronary artery reperfusion (e.g., thrombolytic agents) for prevention of ischemic complications of STEMI^† (e.g., death, reinfarction, stroke).

The American College of Cardiology Foundation (ACCF) and AHA state that patients with STEMI undergoing thrombolytic therapy should receive an anticoagulant (e.g., heparin, enoxaparin, fondaparinux) for ≥48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization is performed. Enoxaparin is preferred over heparin if extended anticoagulation (>48 hours) is necessary.

Acute Ischemic Complications of PCI

Used to reduce the risk of thrombotic complications in patients undergoing PCI. Used in conjunction with aspirin and other standard therapy (e.g., GP IIb/IIIa-receptor inhibitors, P2Y12 receptor antagonists).

Use of a parenteral anticoagulant is recommended in patients undergoing PCI to prevent thrombus formation during the procedure. IV heparin is recommended by AHA, the American College of Cardiology Foundation (ACCF), and the Society for Cardiovascular Angiography and Interventions (SCAI) as an appropriate choice of anticoagulant.

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Reduction in the risk of acute cardiac ischemic events (death and/or MI) in patients with NSTE ACS (unstable angina or non-ST-segment-elevation MI [NSTEMI])^†.

Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blocking agents [β-blockers], P2Y12 receptor antagonists).

Initial parenteral anticoagulants with established efficacy in patients with NSTE ACS include enoxaparin, heparin, bivalirudin (only in patients managed with an early invasive strategy), and fondaparinux.

In patients who will undergo CABG, if heparin is already being administered, continue during surgery. If patient is receiving other anticoagulants (enoxaparin, fondaparinux, or bivalirudin), discontinue other anticoagulant and use heparin during CABG.

In patients in whom conservative medical therapy is selected as a postangiographic management strategy, recommendations for continued antiplatelet and anticoagulant therapy generally are based on the presence of CAD.

Treatment of Cerebral Venous Sinus Thrombosis

May be used for treatment of acute cerebral venous sinus (sinovenous) thrombosis^† in adults. May convert to oral anticoagulant therapy once patient is stabilized.

Recommended by ACCP as an option for initial anticoagulation in children with cerebral venous sinus thrombosis^† without substantial intracranial hemorrhage. Also has been suggested for use in such children with substantial hemorrhage.

Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWH or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke^†; those with additional risk factors for venous thromboembolism are more likely to benefit.

ACCP suggests thromboprophylaxis with an LMWH (in prophylactic dosages), sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke^† and restricted mobility; LMWH is preferred over heparin.

Prophylactic-dose heparin usually initiated within 48 hours of onset of stroke and continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.

Also has been used for initial management of acute arterial ischemic stroke in children^† until dissection and embolic causes have been excluded.

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy^†, ACCP recommends ongoing antithrombotic therapy (e.g., heparin) for 3 months.

Heparin may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source.

Perioperative Management of Antithrombotic Therapy

Used in the perioperative management of patients who require temporary interruption of long-term warfarin therapy for surgery or other invasive procedures.

ACCP suggests perioperative use of an LMWH or IV heparin (bridging anticoagulation) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves depending on their risk of developing thromboembolism without warfarin therapy.

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.

Anticoagulant in Blood Transfusions, Blood Samples, and Other Procedures

Used as an in vitro anticoagulant in blood transfusions.

Used for anticoagulation during extracorporeal circulation and dialysis procedures.

Related/similar drugs

amlodipine, lisinopril, metoprolol, aspirin, carvedilol, Eliquis, propranolol

Heparin Dosage and Administration

General

Laboratory Monitoring of Therapy

• Individualize dosage carefully based on clinical and laboratory findings. The generally accepted therapeutic range for the aPTT during full-dose IV or sub-Q heparin therapy is 1.5–2 times the control value in seconds. The generally accepted therapeutic range for the activated clotting time (ACT) is 2.5–3 times the control value in seconds.

• Laboratory monitoring of coagulation tests usually not performed with fixed low-dose sub-Q heparin therapy because such tests are generally unaffected or only minimally prolonged. If monitoring is required, it is best performed on samples drawn 4–6 hours after injections.

• With continuous IV infusion, perform coagulation tests prior to initiation of therapy, approximately every 4 hours during the early stages of therapy, and daily thereafter.

• With intermittent IV injection, perform coagulation tests prior to each injection during the early stages of therapy, and at appropriate intervals thereafter.

• Perform periodic platelet counts, hematocrit, and tests for occult blood in stool during the entire course of therapy.

Conversion to Oral Anticoagulation

• When warfarin is indicated for follow-up therapy after initial therapy with heparin, overlap therapy for a minimum of 5 days and until INR is at least 2 for ≥24 hours.

• When converting to oral dabigatran in patients currently receiving heparin therapy by continuous IV infusion, administer first dose of dabigatran, then immediately discontinue heparin infusion; for those currently receiving intermittently dosed IV heparin therapy, initiate dabigatran within 2 hours prior to what would have been the time of the next scheduled heparin dose.

• Some manufacturers recommend abrupt discontinuance of heparin therapy after confirmation of adequate response to warfarin. However, some clinicians recommend gradual discontinuance of heparin infusions (e.g., reducing the rate by 50% over 6 hours and then discontinuing over the next 12 hours) because of concern about possible rebound thrombosis.

Administration

Administer by IV infusion, intermittent IV injection, or deep sub-Q (intrafat) injection. Do not administer IM because of frequency of hematoma at injection site.

Do not use heparin lock flush solutions for systemic anticoagulation. Conversely, do not use heparin sodium injections as catheter lock flush products.

Use preservative-free formulations in neonates and infants, and also in pregnant and nursing women, if available. (See Pediatric Use under Cautions.)

Effective May 1, 2013, USP changed its labeling standard for Heparin Sodium Injection, USP and Heparin Lock Flush Solution, USP to require that labels of these products clearly state the strength of the entire container (amount of heparin per total volume of container), followed in close proximity by the strength per mL in parentheses. Carefully check the labels on all heparin products for correct formulation and strength prior to dispensing and administering the drug.

IV Administration

For solution and drug compatibility information, see Compatibility Under Stability.

Dilution

When adding heparin to a solution for continuous IV infusion, invert the container at least 6 times to ensure adequate mixing and to prevent pooling of the drug in solution.

Sub-Q Administration

Inject with a 25- or 26-gauge needle sub-Q deeply above the iliac crest or into the abdominal fat layer, or arm to minimize tissue trauma.

Intracatheter Instillation

Instill a quantity of heparin lock flush solution (e.g., containing 10 or 100 units/mL) sufficient to fill the indwelling venipuncture device into the lumen of the device following the initial placement of the device in the vein and after each use. Consult device manufacturer’s instructions for specific directions.

When the indwelling venipuncture device is used for repeated withdrawal of blood samples for laboratory analysis and the presence of heparin or 0.9% sodium chloride is likely to alter results of the analysis, aspirate and discard heparin lock flush solution from the device before withdrawing the blood sample. After the blood sample is drawn, may instill another dose of heparin lock flush solution into the device.

Following injection of heparin lock flush solution from a single-dose vial into an indwelling venipuncture device, discard unused portions of the solution. Multiple-dose vials are available for repeated use.

Dosage

Available as heparin sodium; dosage is expressed in terms of heparin sodium in USP units. One USP unit is equivalent to one international unit (IU).

Dosage requirements for full-dose therapy vary greatly among individuals; carefully individualize dosage based on the clinical and laboratory findings.

Pediatric Patients

Treatment of DVT and PE

IV

Because of a lack of adequate and well-controlled studies, dosage recommendations in pediatric patients are generally based on clinical experience. In children receiving full-dose (therapeutic) heparin, ACCP suggests a dosage sufficient to achieve an anti-factor Xa concentration of 0.35–0.7 units/mL or prolong the aPTT to a corresponding anti-factor Xa range or to a protamine titration range of 0.2–0.4 units/mL. Initial treatment for at least 5 days recommended. Convert to oral anticoagulation (e.g., warfarin) or an LMWH, or continue with heparin for ongoing therapy. (See Conversion to Oral Anticoagulation under Dosage and Administration.)

Initial loading dose of 75–100 units/kg (by direct IV injection over 10 minutes) has been suggested. Follow with a maintenance IV infusion of 25–30 units/kg per hour in infants or 18–20 units/kg per hour in children >1 year of age; appropriate maintenance dosage appears to be age dependent, with infants <2 months having the highest requirements (e.g., average of 28 units/kg per hour) and older children having lower requirements (e.g., average of 20 units/kg per hour in children >1 year of age). Although not preferred, a maintenance dosage of 75–100 units/kg every 4 hours by intermittent IV administration also has been used.

Individualize initial dosing strategy in children based on risk of thrombosis and risk of bleeding; in general, withhold or reduce loading doses if there are substantial bleeding risks and avoid long-term use of heparin.

Arterial Thromboembolism

IV

For neonates and children requiringcardiac catheterization via an artery^†: 100 units/kg by direct IV injection recommended by ACCP; additional doses may be required in prolonged procedures.

Neonates or children with femoral artery thrombosis associated with cardiac catheterization: Therapeutic-dose IV heparin recommended.

Disseminated Intravascular Coagulation

IV

25–50 units/kg given by IV infusion or IV injection every 4 hours. Discontinue after 4–8 hours if there is no improvement.

Thrombosis Associated with Indwelling Venous or Arterial Devices

IV

For thromboprophylaxis of central venous access devices^† in neonates, ACCP recommends 0.5 units/kg per hour as a continuous infusion.

For thromboprophylaxis of umbilical arterial catheters in neonates, ACCP suggests low-dose infusion (0.25–1 units/mL) through the catheter for a total dosage of 25–200 units/kg per day.

For thromboprophylaxis in neonates and children with peripheral arterial catheters, ACCP recommends continuous low-dose infusion (5 units/mL at 1 mL/hour).

Adults

Treatment of DVT and PE

IV, then Sub-Q

Full-dose intermittent therapy (68-kg adult): 5000 units by IV injection initially, then 10,000–20,000 units sub-Q for 1 dose, followed by 8000–10,000 units sub-Q every 8 hours or 15,000–20,000 units sub-Q every 12 hours.

IV

Full-dose continuous therapy (68-kg adult): 5000 units initial loading dose by IV injection, then 20,000–40,000 units in 1 L of compatible IV solution infused over 24 hours recommended by some manufacturers.

Full-dose intermittent therapy (68-kg adult): 10,000 units initial loading dose (either undiluted or diluted in 50 or 100 mL of 0.9% sodium chloride injection), then 5000–10,000 units every 4–6 hours recommended by some manufacturers.

ACCP suggests a weight-adjusted dosage (loading dose of 80 units/kg followed by continuous infusion of 18 units/kg per hour) or a fixed dosage (loading dose of 5000 units followed by continuous infusion of 1000 units/hour). Although the aPTT can be used to monitor either dosage regimen, ACCP states there is no evidence that monitoring improves clinical outcomes.

Sub-Q

For outpatients receiving sub-Q therapy, ACCP suggests weight-based dosing (initial dose of 333 units/kg followed by 250 units/kg twice daily) without monitoring.

General Surgery Thromboprophylaxis

Sub-Q

Usual dosage is 5000 units administered 2 hours prior to surgery and every 8–12 hours after surgery for 7 days or until patient is fully ambulatory, whichever is longer.

Thromboembolism During Pregnancy

Sub-Q

Women with APLA syndrome and a history of multiple pregnancy losses: Antepartum administration of sub-Q heparin in a prophylactic or intermediate dosage in combination with low-dose aspirin (75–100 mg daily) has been recommended.

Pregnant women with mechanical prosthetic heart valves: Initially, 17,500–20,000 units every 12 hours and adjusted to maintain the mid-interval aPTT at least twice the control value or anti-factor Xa concentration of 0.35–0.7 units/mL throughout pregnancy suggested.

Alternatively, in pregnant women with mechanical prosthetic heart valves, 17,500–20,000 units every 12 hours adjusted to maintain the mid-interval aPTT at least twice the control value or an anti-factor Xa concentration of 0.35–0.7 units/mL until week 13 of pregnancy, then switch to warfarin until close to delivery when heparin may be resumed.

Pregnant women with atrial fibrillation and additional risk factors for thromboembolism: 10,000–20,000 units every 12 hours with dosage adjusted to maintain the mid-interval aPTT (6 hours after dose) at 1.5 times the control value during the first trimester and last month of pregnancy.

IV

Pregnant women with atrial fibrillation and additional risk factors for thromboembolism: Adjusted-dose continuous therapy suggested to maintain the aPTT at 1.5–2 times control value during first trimester and last month of pregnancy.

Perioperative Management of Antithrombotic Therapy

IV

If heparin is used for bridging anticoagulation in patients who require temporary interruption of warfarin therapy (e.g., for surgery or other invasive procedure), ACCP recommends therapeutic dosages (e.g., continuous infusion adjusted to maintain an aPTT of approximately 1.5–2 times the control value); however, other dosage regimens have been used.

ACCP suggests that heparin be discontinued approximately 4–6 hours prior to surgery.

Administer postoperative anticoagulation with caution and only when hemostasis established.

Disseminated Intravascular Coagulation

IV

50–100 units/kg by IV infusion or IV injection every 4 hours. Discontinue after 4–8 hours if there is no improvement.

Thrombosis Associated with Indwelling Venipuncture Devices

Intracatheter Instillation

Inject a quantity of heparin lock flush solution (e.g., containing 10 or 100 units/mL) sufficient to fill the device after each use. (See Intracatheter Instillation under Dosage and Administration: Administration.)

STEMI

IV

Conjunctive therapy with fibrin-selective thrombolytic agents: Initially, 60 units/kg (maximum 4000 units) loading dose.

Maintenance dosage: 12 units/kg per hour (maximum 1000 units/hour), adjusted to maintain a therapeutic aPTT (1.5–2 times control value or approximately 50–70 seconds) for 48 hours or until revascularization.

IV or Sub-Q

Acute MI and concurrent atrial fibrillation: Continuous IV infusion or intermittent sub-Q injection recommended in a dosage sufficient to prolong aPTT to 1.5–2 times the control value.

Cardiac and Arterial Surgery Thromboprophylaxis

IV

Total body perfusion for open-heart surgery: Initially, ≥150 units/kg. Administer 300 units/kg for procedures estimated to last <1 hour. Administer 400 units/kg for those procedures estimated to last >1 hour.

Acute Ischemic Complications of PCI

IV

PCI without concurrent GP IIb/IIIa-receptor inhibitor: In patients who have not received prior anticoagulant therapy, a loading dose of 70–100 units/kg targeted to achieve an ACT of 250–300 seconds with the HemoTec device or 300–350 seconds with the Hemochron device suggested. If patient has received prior anticoagulant therapy, administer additional doses as needed to achieve an ACT of 250–300 seconds with the HemoTec device or 300–350 seconds with the Hemochron device.

PCI with concurrent GP IIb/IIIa-receptor inhibitors: In patients who have not received prior anticoagulant therapy, a loading dose of 50–70 units/kg targeted to an ACT of 200–250 seconds suggested. If patient has received prior anticoagulant therapy, administer additional doses (e.g., 2000–5000 units) as needed to achieve an ACT of 200–250 seconds.

Discontinue therapy after successful PCI procedures. The femoral sheath generally is removed when ACT <150–180 seconds or when aPTT <50 seconds.

NSTE ACS

IV

ACCF/AHA/ACC recommends a weight-adjusted dosing regimen (e.g., 60 units/kg [maximum 4000 units] loading dose followed by continuous infusion of 12 units/kg per hour [maximum 1000 units/hr]). Initiate therapy as soon as possible upon presentation. Optimum duration of therapy not established; in clinical trials, heparin was continued for 2–5 days.

Anticoagulant in Blood Transfusions and Blood Samples

In vitro

In blood transfusions, add 7500 units to 100 mL of 0.9% sodium chloride injection and then add 6–8 mL of this solution to each 100 mL of whole blood.

When used as an in vitro anticoagulant for blood samples, add 70–150 units to each 10–20 mL of whole blood.

Extracorporeal Dialysis

Consult equipment manufacturer's operating instructions; if not available, dose of 25–30 units/kg, followed by infusion of 1500–2000 units/hour is suggested based on pharmacodynamic data.

Prescribing Limits

Adults

STEMI

IV

Conjunctive therapy with fibrin-selective thrombolytic agents: Maximum 4000 units loading dose.

Maintenance dosage: Maximum 1000 units/hour.

Special Populations

Geriatric Patients

Patients >60 years of age may require a lower dosage. Consider lower dosages in geriatric patients undergoing PCI, particularly when combined with GP IIb/IIIa-receptor inhibitors.

Women

Consider lower dosages in women undergoing PCI, particularly when combined with GP IIb/IIIa-receptor inhibitors.

Cautions for Heparin

Contraindications

• Uncontrollable bleeding, unless such bleeding is secondary to disseminated intravascular coagulation.

• Severe thrombocytopenia, history of HIT, or HIT with thrombosis.

• Inability to perform suitable blood coagulation tests at required intervals in patients receiving full-dose therapy. Lack of such tests generally is not a contraindication for fixed low-dose therapy, since monitoring of coagulation tests usually is not required.

• Known hypersensitivity to heparin or pork products. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Hematologic Effects

Hemorrhage can range from minor local ecchymoses to major hemorrhagic complications. Bleeding may occur at any site; some hemorrhagic complications may be difficult to detect.

Use with extreme caution in patients with an increased risk of hemorrhage. Such patients include those with subacute bacterial endocarditis; ulcerative GI lesions; hemorrhagic blood dyscrasias (e.g., hemophilia, some vascular purpuras, thrombocytopenia); menstruation; hepatic disease with impaired hemostasis; severe hypertension; major surgery, especially involving the eye, brain, or spinal cord; continuous tube drainage of the stomach or small intestine; and spinal tap or spinal anesthesia. Screen patients prior to treatment initiation to rule out bleeding disorders.

Monitor patients with appropriate coagulation tests just prior to surgery. Discontinue therapy immediately if hemorrhage occurs or if coagulation tests are unduly prolonged. Nosebleed, hematuria, or tarry stools may be noted as the first sign of bleeding or overdosage. Easy bruising or petechiae may precede frank bleeding. If severe hemorrhage or overdosage occurs, administer protamine sulfate immediately. Blood transfusions may also be required following massive blood loss.

If signs and symptoms of acute adrenal hemorrhage and insufficiency occur, measure plasma cortisol concentrations. Initiate vigorous therapy with IV corticosteroids after discontinuance. Do not delay initiation of corrective therapy until laboratory confirmation of the diagnosis, since any delay may be fatal.

Perform periodic hematocrit and tests for occult blood in stool during the entire course of therapy.

Obtain baseline aPTT value prior to insertion of an indwelling venipuncture device (e.g., heparin lock) since repeated injections of small doses of heparin sodium can alter aPTT results.

Risk of thrombocytopenia, including HIT (immune-mediated reaction caused by development of IgG platelet-aggregating antibodies). (See HIT under Cautions and also see Contraindications under Cautions.) Monitor thrombocytopenia of any degree closely. Mild thrombocytopenia (platelet count >100,000/mm³) may remain stable or reverse with continued therapy. If clinically important HIT occurs, discontinue the drug immediately and substitute a nonheparin anticoagulant (e.g., argatroban, bivalirudin).

Sensitivity Reactions

Hypersensitivity

Generally contraindicated in patients who are hypersensitive to the drug. Patients with documented hypersensitivity should be given the drug only in clearly life-threatening situations.

Major Toxicities

HIT

Risk of HIT; may lead to severe thromboembolic complications including DVT, cerebral vein thrombosis, limb ischemia, mesenteric thrombosis, renal artery thrombosis, skin necrosis, gangrene of the extremities (possibly requiring amputation), MI, PE, stroke, and possibly, death. Can occur even with heparin lock flush solutions. Usually evident 5–10 days after exposure to heparin, but can occur more rapidly (e.g., within 24 hours) or as late as several weeks after discontinuance of therapy.

If HIT with or without thrombosis is diagnosed or strongly suspected, discontinue all sources of heparin (including heparin flushes) and substitute a nonheparin anticoagulant (e.g., argatroban, bivalirudin). Initiate conversion to warfarin therapy only after substantial recovery from acute HIT has occurred (i.e., platelet counts ≥150,000/mm³). The manufacturer recommends against future use of heparin in patients who experience HIT, particularly within 3–6 months following the event and if HIT antibodies are still present.

Evaluate patients who develop thrombocytopenia or thrombosis after treatment discontinuance for HIT and HIT with thrombosis.

General Precautions

Heparin Resistance

Increased resistance to the antithrombotic effects of heparin reported; associated with fever, MI, thrombophlebitis, infections with thrombosing tendencies, thrombosis, antithrombin III deficiency, malignant neoplasms, and surgery (i.e., postoperatively).

Dispensing and Administration Precautions

Fatal medication errors (including in pediatric patients) have occurred as a result of confusion between different formulations of heparin, in particular with heparin sodium injection and catheter lock flush vials. Ensure accuracy of dispensing; take appropriate measures to carefully distinguish between heparin formulations when dispensing and review all labels for correct drug name, strength, and volume.

Report dispensing errors to manufacturers or directly to FDA MedWatch program by phone (800-FDA-1088), fax (800-FDA-1078), or internet ([Web]).

Specific Populations

Pregnancy

Category C. Manufacturers recommend use of a preservative (benzyl alcohol)-free formulation in pregnant women.

Lactation

Not likely to be distributed into milk. However, if benzyl alcohol is present in maternal serum, it is likely to distribute into milk and be absorbed by a nursing infant. Caution is advised when using heparin in nursing women; manufacturers recommend use of a preservative (benzyl alcohol)-free formulation.

ACCP recommends that heparin be continued in nursing women who are already receiving such therapy.

Pediatric Use

There are no adequate and well-controlled studies evaluating use of heparin in pediatric patients.

Some heparin sodium injections and heparin lock flush solutions contain benzyl alcohol as a preservative. Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity (e.g., “gasping syndrome”) in neonates. Manufacturers recommend use of preservative-free formulations in neonates and infants. AAP states that presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates. If other benzyl alcohol-containing preparations are being used, consider the total daily metabolic load of benzyl alcohol from all sources.

Fatal medication dispensing errors reported in pediatric patients, including neonates. Take appropriate precautions when dispensing and administering the drug. (See Dispensing and Administration Precautions under Cautions.)

Because of the potential risk of systemic anticoagulation, avoid use of heparin lock flush solutions containing 100 units/mL in neonates and in infants <10 kg. Caution also advised when using heparin lock flush solutions containing 10 units/mL in premature infants <1 kg who are receiving frequent flushes.

Geriatric Use

Manufacturers state that risk of hemorrhage may be higher in patients >60 years of age, particularly women. (See Geriatric Patients and see Women under Dosage and Administration.)

Renal Impairment

Patients with renal failure may be at increased risk of bleeding complications.

Common Adverse Effects

Hemorrhage, thrombocytopenia, HIT or HIT with thrombosis, injection site irritation, general hypersensitivity reactions, elevated aminotransferase concentrations.

Drug Interactions

Drugs Affecting Platelet Function

Potential pharmacodynamic interaction (increased risk of bleeding complications). Use with caution.

Specific Drugs and Laboratory Tests

Heparin Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration achieved 2–4 hours following sub-Q administration.

Onset

Immediate following direct IV injection or IV infusion of full doses.

Within 20–60 minutes following deep sub-Q injection.

Duration

Heparin lock flush solutions: Anticoagulation maintained within the device for generally up to 4 hours.

Special Populations

Plasma heparin concentrations may be increased and aPTTs more prolonged in geriatric (>60 years of age) patients compared with younger adults.

Distribution

Extent

Does not cross the placenta and is not distributed into milk.

Plasma Protein Binding

Extensively bound to LDL, globulins, and fibrinogen. May contribute to the lack of relationship between duration of anticoagulant effect and blood concentration half-life.

Elimination

Metabolism

Cleared from the circulation mainly by the reticuloendothelial system. May be partially metabolized in the liver to uroheparin, which is partially desulfated heparin.

Elimination Route

Small fraction excreted in urine as unchanged drug.

Half-life

1–2 hours in healthy adults. Half-life increases with increasing doses. Plasma half-life averages 56, 96, and 152 minutes following IV heparin sodium doses of 100, 200, or 400 units/kg, respectively. Shorter plasma half-life in patients with pulmonary embolism than in healthy individuals or patients with other thrombotic disorders.

Special Populations

Decreased plasma half-life in patients with liver impairment; half-life may be prolonged in patients with cirrhosis.

Half-life may be slightly prolonged in anephric patients or patients with severe renal impairment.

Stability

Storage

Parenteral

Solution for Injection

Heparin lock flush solutions: 20–25°C.

Heparin sodium injections: 20–25°C.

Heparin sodium injection in 5% dextrose or in 0.45 or 0.9% sodium chloride injection: 20–25°C; protect from freezing.

Compatibility

Parenteral

Solution CompatibilityHID

When administered in a venipuncture device with an incompatible drug, flush the entire device with 0.9% sodium chloride injection, a compatible isotonic injection, or sterile water prior to and immediately after administration of the incompatible drug. Inject another dose of heparin lock flush solution (e.g., 1 mL of 10 units/mL) into the device after the second flush.

Drug Compatibility

Actions

• Acts as a catalyst to markedly accelerate the rate at which antithrombin III (heparin cofactor) neutralizes thrombin and activated coagulation factor X (X_a). Low-dose therapy neutralizes X_a which prevents the conversion of prothrombin to thrombin. Low doses of heparin have very little effect on thrombin and exert a measurable antithrombogenic effect only if thrombin formation has not already occurred.

• Full-dose therapy neutralizes thrombin, which prevents the conversion of fibrinogen to fibrin. Also prevents the formation of a stable fibrin clot by inhibiting activation of fibrin stabilizing factor. Low-dose or full-dose therapy inhibits thrombus formation when stasis is induced. Full-dose therapy may prevent extension of existing thrombi.

• Full-dose therapy prolongs several coagulation assays including the ACT, aPTT, plasma recalcification time, PT, thrombin time, and whole blood clotting time. Clotting time is generally unaffected or only minimally prolonged by low-dose therapy.

Advice to Patients

• Importance of reporting any unexplained bleeding or bruising to clinician.

• Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary and herbal supplements, and any concomitant illnesses.

• Importance of women informing clinician if they are or plan to become pregnant or to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• How and where is Heparin injection given?

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