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Heparin

Medically reviewed by Drugs.com. Last updated on Mar 18, 2019.

Pronunciation

(HEP a rin)

Index Terms

  • Heparin Calcium
  • Heparin Lock Flush
  • Heparin Sodium
  • Heparinized Saline

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 25,000 units (500 mL); 25,000 units/500 mL in NaCl 0.45% (500 mL)

Solution, Injection, as sodium:

Generic: 1000 units (500 mL); 2000 units (1000 mL); 12,500 units (250 mL); 25,000 units (250 mL); 1000 units/mL (1 mL, 10 mL, 30 mL); 5000 units/mL (1 mL, 10 mL); 10,000 units/mL (1 mL, 4 mL, 5 mL); 20,000 units/mL (1 mL); 1000 units (500 mL)

Solution, Injection, as sodium [preservative free]:

Generic: 1000 units/mL (2 mL); 5000 units/mL (1 mL); 5000 units/0.5 mL (0.5 mL)

Solution, Intravenous, as sodium:

Generic: 10,000 units (250 mL [DSC]); 12,500 units (250 mL [DSC]); 20,000 units (500 mL); 25,000 units (250 mL, 500 mL); 1 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL); 10 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL); 100 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL); 25,000 units/250 mL in Dextrose 5% (250 mL); 25,000 units/250 mL in NaCl 0.45% (250 mL); 25,000 units/500 mL in Dextrose 5% (500 mL)

Solution, Intravenous, as sodium [preservative free]:

Generic: 10 units/mL (1 mL [DSC], 3 mL, 5 mL); 100 units/mL (1 mL [DSC], 3 mL, 5 mL)

Solution Prefilled Syringe, Injection, as sodium [preservative free]:

Generic: 5000 units/0.5 mL (0.5 mL)

Pharmacologic Category

  • Anticoagulant
  • Anticoagulant, Heparin

Pharmacology

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

Absorption

Oral, rectal: Erratic at best from these routes of administration; SubQ absorption is also erratic, but considered acceptable for prophylactic use

Distribution

Premature neonates (data based on single dose of 100 units/kg within 4 hours of birth) (McDonald 1981): Inversely proportional to gestational age

GA 25 to 28 weeks: 81 ± 41 mL/kg

GA 29 to 32 weeks: 73.3 ± 24.8 mL/kg

GA 33 to 36 weeks: 57.8 ± 32.2 mL/kg

Adults: Following a single 75 unit/kg dose: 36.6 ± 7.4 mL/kg (McDonald 1981)

Metabolism

Complex; thought to occur by depolymerization and desulphation via the reticuloendothelial system primarily in the liver and spleen (ACCP [Garcia 2012]; Dawes 1979; Estes 1980; Kandrotas 1992)

Excretion

Urine (small amounts as unchanged drug); Note: At therapeutic doses, elimination occurs rapidly via nonrenal mechanisms. With very high doses, renal elimination may play more of a role; however, dosage adjustment remains unnecessary for patients with renal impairment (Kandrotas 1992).

Clearance: Age-related changes; within neonatal population, slower clearance with lower GA; however, when compared to adults, the overall clearance in neonatal and pediatric patients is faster than adults (ACCP [Monagle 2012 ]; McDonald 1981)

Onset of Action

Anticoagulation: IV: Immediate; SubQ: ~20 to 30 minutes

Half-Life Elimination

Age-related: Shorter half-life reported in premature neonates compared to adult patients

Premature neonates GA 25 to 36 weeks (data based on single dose of 100 units/kg within 4 hours of birth): Mean range: 35.5 to 41.6 minutes (McDonald 1981)

Dose-dependent: IV bolus: 25 units/kg: 30 minutes (Bjornsson 1982); 100 units/kg: 60 minutes (de Swart 1982); 400 units/kg: 150 minutes (Olsson 1963)

Mean: 1.5 hours; Range: 1 to 2 hours; affected by obesity, renal function, malignancy, presence of pulmonary embolism, and infections

Note: At therapeutic doses, elimination occurs rapidly via nonrenal mechanisms. With very high doses, renal elimination may play more of a role; however, dosage adjustment remains unnecessary for patients with renal impairment (Kandrotas 1992).

Special Populations: Renal Function Impairment

The half-life may be increased.

Special Populations: Hepatic Function Impairment

The half-life may be increased or decreased.

Special Populations: Elderly

Plasma levels may be higher.

Use: Labeled Indications

Anticoagulation: Prophylaxis and treatment of thromboembolic disorders (eg, venous thromboembolism, pulmonary embolism) and thromboembolic complications associated with atrial fibrillation; prevention of clotting in arterial and cardiac surgery; as an anticoagulant for extracorporeal circulation and dialysis procedures

Note: Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for systemic anticoagulant therapy.

Off Label Uses

Interstitial cystitis (bladder pain syndrome)

Intravesical heparin alone or in combination with alkalinized lidocaine for the management of interstitial cystitis/bladder pain syndrome has been studied in controlled and noncontrolled trials demonstrating efficacy rates of 56% to 94%. American Urological Association guidelines recommend intravesical heparin as a second-line treatment option (uncertain risk-benefit ratio) that may provide benefit in a subset of patients.

Non-ST-elevation acute coronary syndrome

Based on the American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), heparin is effective and recommended as an alternative to enoxaparin, fondaparinux, or bivalirudin for the treatment of patients presenting with NSTE-ACS undergoing an invasive strategy or as an alternative to enoxaparin or fondaparinux in patients presenting with NSTE-ACS undergoing an ischemia-guided strategy.

Percutaneous coronary intervention (PCI)

Based on the American College of Cardiology Foundation/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACCF/AHA/SCAI) guidelines for PCI, heparin is effective and recommended as an alternative to other anticoagulants (eg, enoxaparin, bivalirudin, fondaparinux) to prevent thrombus formation during PCI.

ST-elevation myocardial infarction

Based on the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of ST-elevation myocardial infarction (STEMI), heparin is effective and recommended as an alternative to enoxaparin or fondaparinux for the treatment of patients presenting with STEMI receiving fibrinolytic therapy.

Additional Off-Label Uses

According to the antithrombotic guidelines from the American College of Chest Physicians (ACCP), heparin is recommended as an anticoagulant in several conditions in addition to those above, such as the following: Superficial vein thrombosis, nonbacterial thrombotic endocarditis, cerebral venous sinus thrombosis, and acute arterial emboli or thrombosis. See the ACCP antithrombotic guidelines for more details.

Contraindications

Hypersensitivity to heparin or any component of the formulation (unless a life-threatening situation necessitates use and use of an alternative anticoagulant is not possible); severe thrombocytopenia; history of heparin-induced thrombocytopenia; history of heparin-induced thrombocytopenia with thrombosis; uncontrolled active bleeding except when due to disseminated intravascular coagulation; cases where the administration of sodium or chloride could be clinically detrimental (applies to large volume heparin 2 unit/mL IV solutions only); not for use when appropriate blood coagulation tests cannot be obtained at appropriate intervals (applies to full-dose heparin only).

Note: Some products contain benzyl alcohol as a preservative; their use in neonates, infants, or pregnant or breastfeeding women is contraindicated by some manufacturers.

Dosing: Adult

Note: For weight-based dosing, use of institution specific dosing nomograms are recommended. Many concentrations of heparin are available ranging from 1 unit/mL to 20,000 units/mL. Carefully examine each prefilled syringe or vial prior to use and ensure that the correct concentration is chosen. Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Ischemic heart disease: Note: If clinically indicated, a glycoprotein (GP) IIb/IIIa inhibitor (eg, abciximab, eptifibatide, tirofiban) may be administered in combination with parenteral anticoagulation (eg, heparin) and other antiplatelet agents (eg, aspirin and a P2Y12 inhibitor [eg, clopidogrel, prasugrel, ticagrelor]) during percutaneous coronary intervention (PCI) for ischemic heart disease. However, GP IIb/IIIa inhibitor use may be associated with more bleeding complications (Stone 2006; Stone 2008).

Acute coronary syndromes (ACS):

ST-elevation myocardial infarction (STEMI) (off-label use):

Adjunct to PCI:

No planned GP IIb/IIIa inhibitor use: IV: Bolus 70 to 100 units/kg to achieve ACT of 250 to 300 seconds (goal ACT may vary depending on point of care device); redose as needed to maintain goal ACT throughout procedure (ACCF/AHA [Levine 2011]; ACCF/AHA [O’Gara 2013]; Erlinge 2017; Han 2015; Shahzad 2014; Steg 2013; Valgimigli 2015).

Planned GP IIb/IIIa inhibitor use: IV: Bolus 50 to 70 units/kg to achieve ACT of 200 to 250 seconds (regardless of point of care device); redose as needed to maintain goal ACT throughout procedure (ACCF/AHA [Levine 2011]; ACCF/AHA [O’Gara 2013]; Han 2015; Steg 2013; Stone 2008; Valgimigli 2015).

Adjunct to fibrinolysis (eg, full-dose alteplase, reteplase, or tenecteplase): IV: Bolus 60 units/kg (maximum: 4,000 units), followed by 12 units/kg/hour (maximum: 1,000 units/hour); adjust infusion to target aPTT of 1.5 to 2 times control (~50 to 70 seconds). Continue for a minimum of 48 hours or until revascularization (if performed) (ACCF/AHA [O’Gara 2013]; Antman 2006; Wallentin 2003).

No planned reperfusion: Limited data available, some experts recommend: IV: Bolus 50 to 70 units/kg (maximum of 5,000 units), followed by 12 units/kg/hour; adjust infusion to target aPTT of 1.5 to 2 times control (~50 to 70 seconds). Continue for ≥48 hours (Lincoff 2018).

Non-ST-elevation ACS (off-label use):

Ischemia-guided approach: IV: Bolus 60 units/kg (maximum: 5,000 units), followed by 12 units/kg/hour (maximum: 1,000 units/hour); adjust infusion to target aPTT of 1.5 to 2 times control (~50 to 70 seconds). Recommended duration is ≥48 hours or until management changes to an invasive strategy (eg, PCI) (ACCF/AHA [Amsterdam 2014]; Cohen 1997; Cutlip 2018; Ferguson 2004; Stone 2006); if PCI is performed see Percutaneous coronary intervention for dosing guidance.

Invasive approach (adjunct to PCI):

No planned GP IIb/IIIa inhibitor use: IV: Bolus 70 to 100 units/kg to achieve ACT of 250 to 300 seconds (goal ACT may vary depending on point of care device); redose as needed to maintain goal ACT throughout procedure (ACCF/AHA [Amsterdam 2014]; ACCF/AHA [Levine 2011]; Erlinge 2017; Han 2015; Valgimigli 2015).

Planned GP IIb/IIIa inhibitor use: IV: Bolus 50 to 70 units/kg to achieve ACT of 200 to 250 seconds (regardless of point of care device); redose as needed to maintain goal ACT throughout procedure (ACCF/AHA [Amsterdam 2014]; ACCF/AHA [Levine 2011]; Han 2015; Stone 2006; Valgimigli 2015).

Percutaneous coronary intervention (off-label use):

No prior anticoagulant therapy:

No planned GPIIb/IIIa inhibitor use: IV: Initial bolus of 70 to 100 units/kg to achieve ACT of 250 to 300 seconds (goal ACT may vary depending on point of care device); redose as needed to maintain goal ACT throughout procedure. (ACCF/AHA [Levine 2011])

Planned GPIIb/IIIa inhibitor use: Initial bolus of 50 to 70 units/kg to achieve ACT of 200 to 250 seconds (regardless of point of care device used); redose as needed to maintain goal ACT throughout procedure (ACCF/AHA [Levine 2011])

Prior anticoagulant therapy:

Prior anticoagulation with heparin:

No planned GP IIb/IIIa inhibitor use: IV: Redose heparin as needed (eg, 2,000 to 5,000 units) to maintain goal ACT of 250 to 300 seconds throughout procedure (goal ACT may vary depending on point of care device) (ACCF/AHA [Levine 2011])

Planned GP IIb/IIIa inhibitor use: IV: Redose heparin as needed (eg, 2,000 to 5,000 units) to maintain goal ACT of 200 to 250 seconds throughout procedure (regardless of point of care device) (ACCF/AHA [Levine 2011])

Prior anticoagulation with enoxaparin:

If PCI occurs <12 hours after the last SubQ dose of enoxaparin:Refer to Enoxaparin monograph for dosing recommendations.

If PCI occurs >12 hours after the last SubQ dose of enoxaparin: May use an established anticoagulation regimen (eg, full-dose heparin) (ACCF/AHA [Levine 2011]).

Prior anticoagulation with fondaparinux:

No planned GP IIb/IIIa inhibitor use: IV: Bolus 85 units/kg to achieve ACT of 250 to 300 seconds (goal ACT may vary depending on point of care device); redose as needed to maintain goal ACT throughout procedure (Steg 2010).

Planned GP IIb/IIIa inhibitor use: IV: Bolus 60 units/kg to achieve ACT of 200 to 250 seconds (regardless of point of care device); redose heparin as needed to maintain goal ACT throughout procedure (Steg 2010).

Atrial fibrillation (to prevent stroke and systemic embolism): General guidelines pertaining to peri-cardioversion use: IV: Note: If patient is not on another anticoagulant prior to presentation, begin heparin and titrate based on institutional protocol to maintain an aPTT equivalent to anti-Xa activity in the range of 0.3 to 0.7 units/mL (ACCP [Garcia 2012]; ACCP [You 2012]; Bates 2001; Hirsh 1994; Vandiver 2012).

Cardioversion:

Patients with atrial fibrillation >48 hours or unknown duration: Note: Patient should receive therapeutic anticoagulation (usually an oral anticoagulant) for ≥3 weeks prior to cardioversion, regardless of the CHA2DS2-VASc score. Alternatively, a transesophageal echocardiogram (TEE) may be performed and if no thrombus is visualized, cardioversion may be performed within 24 hours (ACC/AHA [January 2019]; ACCP [You 2012]).

Patients with atrial fibrillation <48 hours: Note: Begin heparin at the time of presentation. Cardioversion may be performed without 3 weeks of anticoagulation prior to procedure (ACCP [You 2012]).

Emergency cardioversion in hemodynamically unstable patient: Note: Begin heparin at the time of presentation, but initiation of anticoagulation should not delay emergency cardioversion. Cardioversion may be performed without 3 weeks of anticoagulation prior to procedure (ACC/AHA [January 2019]; ACCP [You 2012]).

Note: In all scenarios, patients should be transitioned to an oral anticoagulant and receive therapeutic anticoagulation for at least 4 weeks after cardioversion (ACCP [You 2012]; Phang 2018).

Cardiopulmonary bypass, anticoagulation: IV: Initial: 300 to 400 units/kg prior to arterial or venous cannulation. Cardiopulmonary bypass may be initiated once ACT is at least 400 to 480 seconds depending on the instrument used (Shore-Lesserson 2018); measure ACT every 30 minutes and administer additional heparin boluses as necessary (Kincaid 2014). Note: An ACT of 400 is adequate for instruments using maximal activation whereas an ACT of 480 is preferred for standard instruments using a single activator (Shore-Lesserson 2018).

Dialysis, anticoagulation of circuit:

Intermittent hemodialysis:

Standard dose: IV: Initial: Bolus 2,000 units; repeat bolus halfway through hemodialysis treatment or may start a continuous infusion of 500 units/hour after the initial bolus; titrate to maintain an ACT of 200 to 250 seconds throughout procedure. If an infusion is used, turn off the infusion 30 minutes before the end of the procedure (Kovalik 2018).

Minimum dose (for patients at high risk for bleeding): IV: Initial: Bolus 500 units; repeat boluses every 30 minutes or may start a continuous infusion of 250 to 500 units/hour after the initial bolus; monitor frequently and titrate to maintain an ACT of 150 to <200 seconds throughout procedure (Kovalik 2018).

Continuous renal replacement therapy (alternative agent): IV: Initial: Bolus 500 to 1,000 units; followed by a continuous infusion of 500 units/hour; titrate to maintain an aPTT of ~45 seconds. (Davenport 2018).

Note: Standard dosing has not been established. Protocols should be individualized based on coagulation abnormalities and risk for bleeding.

Interstitial cystitis (bladder pain syndrome) (off-label use): Intravesical: Note: Various dosage regimens of heparin (20,000 to 50,000 units) alone or with alkalinized lidocaine (1% to 4%) have been used. When lidocaine and heparin are mixed, there is a risk of precipitation if proper alkalinization does not occur. Lidocaine stability and pH should be determined after the components have been mixed, prior to administration.

Single-dose regimen: Instill the combination of 50,000 units of heparin, lidocaine 200 mg, and sodium bicarbonate 420 mg in 15 mL of sterile water into the bladder via catheter and allow to dwell for 30 minutes before draining (Parsons 2012).

Once-weekly dosing regimen: Instill the combination of 20,000 units of heparin, lidocaine 4% (5 mL), and sodium bicarbonate 7% (25 mL) into an empty bladder via catheter once weekly for 12 weeks and allow to dwell for 30 minutes before draining (Nomiya 2013).

Twice-weekly dosing regimen: Instill 25,000 units of heparin (diluted with 5 mL of sterile water) into bladder via catheter twice weekly for 3 months (Kuo 2001).

Maintenance of catheter patency (continuous infusion): Using heparin 2 unit/mL large volume IV solutions, may administer at an infusion rate of 3 mL/hour (equivalent to 6 units/hour); however, rate of infusion dependent upon age, weight, clinical condition of patient, and procedure being employed. Do not use as a "catheter lock flush".

Venous thromboembolism (VTE):

VTE prophylaxis (alternative agent):

Hospitalized medical patients with acute illness at moderate to high risk for VTE (including patients with active cancer): SubQ: 5,000 units every 8 to 12 hours (a frequency of every 12 hours has been used in cancer patients but appears to be less effective); recommended duration is length of hospitalization or until fully ambulatory (ACCP [Kahn 2012]; ASCO [Lyman 2013; Lyman 2015]; Pai 2018a).

Major nonorthopedic surgery (patients with active cancer):Note: Regimens vary and include the following:

SubQ: 5,000 units 2 to 4 hours prior to surgery, then 5,000 units every 8 hours thereafter (a frequency of every 12 hours has been used but appears to be less effective) (ASCO [Lyman 2013])

or

SubQ: 5,000 units every 8 to 12 hours started ~6 to 24 hours after surgery (Bauer 2019a)

Note: The optimal duration of prophylaxis has not been established. It is usually given for a minimum of 7 to 10 days; extending for up to 4 weeks may be reasonable in those undergoing major abdominal or pelvic surgery (ASCO [Lyman 2013]; ASCO Lyman 2015]).

Nonorthopedic surgery (patients without cancer): Note: For patients with moderate and high risk of VTE and low risk of bleeding: SubQ: 5,000 units every 8 to 12 hours, with initial dose given 2 hours prior to surgery. Alternatively, may postpone pharmacologic prophylaxis until after surgery (eg, high bleeding risk) when it is safe to initiate. Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days) (ACCP [Gould 2012]; Pai 2018b).

Orthopedic surgery (eg, hip fracture surgery [HFS]; total hip arthroplasty [THA], or total knee arthroplasty [TKA]): SubQ: 5,000 units every 8 to 12 hours, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved; optimal duration of prophylaxis is unknown but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days; some experts suggest a duration in the lower end of the range (10 to 14 days) for TKA or higher end of range (~30 days) for THA (Falck-Ytter 2012; Pai 2018c). For extended prophylaxis, may transition to an oral anticoagulant or alternative subcutaneous anticoagulant with less frequent dosing (Pai 2018c).

Pregnancy: Note: For patients at moderate and high VTE risk during antepartum and postpartum periods. Dose intensity is individualized based on risks of thrombosis and bleeding complications.

Prophylactic dose:

First trimester: SubQ: 5,000 to 7,500 units every 12 hours (ACOG 2018)

Second trimester: SubQ: 7,500 to 10,000 units every 12 hours (ACOG 2018)

Third trimester: SubQ: 10,000 units every 12 hours (reduce dose if the aPTT is elevated) (ACOG 2018; Bauer 2019b)

Adjusted dose (therapeutic): SubQ: 10,000 units every 12 hours; adjust dose to target an aPTT of 1.5 to 2.5 times control, measured 6 hours after injection; reserved for patients at the highest risk (eg, history of recurrent thrombosis or severe thrombophilia) (ACCP [Bates 2012]; ACOG 2018)

Note: Discontinue heparin ≥12 hours before delivery in patients receiving 7,500 units every 12 hours or 10,000 units every 12 hours. Discontinue heparin ≥24 hours before delivery in patients receiving >10,000 units every 12 hours; consider checking coagulation parameters (eg, aPTT) before delivery; appropriate discontinuation is particularly important if neuraxial anesthesia is planned; may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred (ACOG 2018). Anticoagulation should continue for up to 6 weeks postpartum in high-risk women (ACCP [Bates 2012]).

Deep vein thrombosis and/or pulmonary embolism treatment:

Initial anticoagulation:

Note: Some experts prefer IV heparin for initial therapy in patients who are hemodynamically unstable, have extensive clot burden and who may need invasive procedures or thrombolysis, have renal failure, when discontinuation or reversal is anticipated, or in obese patients when monitoring is desired. In other patients, a low-molecular weight heparin, fondaparinux, rivaroxaban, or apixaban may be used for initial therapy (Lip 2018).

IV: Inpatient setting: 80 units/kg (or alternatively 5,000 units) IV bolus followed by an initial continuous infusion of 18 units/kg/hour (or alternatively 1,000 units/hour) (ACCP [Guyatt 2012]) to maintain an aPTT equivalent to anti-Xa activity in the range of 0.3 to 0.7 units/mL (ACCP [Garcia 2012]; Bates 2001; Hirsh 1994; Vandiver 2012).

SubQ: Unmonitored dosing regimen (alternative for patients who decline IV access and have a contraindication to other anticoagulants): Initial: 333 units/kg, followed by 250 units/kg every 12 hours (ACCP [Guyatt 2012]; Holbrook 2012; Lip 2018)

Long-term (maintenance) anticoagulation: Note: Unfractionated heparin is not a recommended option for long-term (maintenance) anticoagulation; alternative agents are preferred (eg, direct oral anticoagulants, warfarin, low molecular weight heparin [LMWH]) (Hull 2018; ACCP [Kearon 2012]; ACCP [Kearon 2016]).

Transitioning between anticoagulants:

Transitioning from another anticoagulant to IV heparin:

Transitioning from a therapeutic dose of SubQ LMWH or SubQ fondaparinux to a therapeutic dose of IV heparin: Start IV heparin (rate based on indication) 1 to 2 hours before the next dose of LMWH or fondaparinux would have been due. No heparin bolus is needed (Nutescu 2007).

Transitioning from IV heparin to another anticoagulant:

Transitioning from therapeutic dose IV heparin infusion to therapeutic SubQ LMWH or SubQ fondaparinux: Discontinue IV heparin and begin SubQ LMWH or SubQ fondaparinux within 1 hour. Note: If aPTT is not in therapeutic range at the time heparin is discontinued, consult local protocol (Nutescu 2007).

Transitioning from VTE prophylaxis regimens to therapeutic IV heparin: Therapeutic IV heparin (rate based on indication) should be started without delay. An IV heparin bolus/loading dose (based on indication) may be used if indicated.

Transitioning from therapeutic dose IV heparin to warfarin for VTE treatment: Start warfarin on the first or second treatment day and overlap with IV heparin until INR is ≥2 for ≥2 measurements ~24 hours apart (duration of overlap is usually 4 to 5 days) (ACCP [Ageno 2012]; Hull 2018).

Transitioning from therapeutic dose IV heparin to warfarin for nonvalvular atrial fibrillation: In patients not at high risk of immediate thromboembolism, warfarin is usually started without parenteral anticoagulant (ie, no bridging). In patients at high risk of immediate thromboembolism, overlapping with IV heparin until INR is within therapeutic range (bridging) may be considered (ACCP [You 2012]).

Transitioning from therapeutic dose IV heparin to a direct oral anticoagulant (DOAC): Start DOAC when the parenteral anticoagulant infusion is stopped (consult local protocol if the aPTT is above the target range). Note: In treatment of VTE, some DOACs (dabigatran, edoxaban) require 5 days of parenteral anticoagulation prior to transitioning (Hull 2018).

Dosing: Geriatric

Patients >60 years of age may have higher serum levels and clinical response (longer aPTTs) as compared to younger patients receiving similar dosages. Lower dosages may be required.

Dosing: Pediatric

Note: Many concentrations of heparin are available and range from 1 to 20,000 units/mL. Carefully examine each prefilled syringe, bag, or vial prior to use to ensure that the correct concentration is chosen. Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Prophylaxis:

Central line flush; patency (intermittent doses): Limited data available (ACCP [Monagle 2012]; Conway 2014; Lee 2005): Infants, Children, and Adolescents: When using intermittent flushes of heparin to maintain patency of single and double lumen central catheters, various recommendations exist; refer to institution specific protocols. Capped polyvinyl chloride catheters and peripheral heparin locks require flushing more frequently (eg, every 6 to 8 hours). Volume of heparin flush is usually similar to volume of catheter (or slightly greater). Dose of heparin flush used should not approach therapeutic unit per kg dose. Additional flushes should be given when stagnant blood is observed in catheter, after catheter is used for drug or blood administration, and after blood withdrawal from catheter.

ECMO venoarterial (VA)/Cardiac, anticoagulation: Note: While used to prevent thrombosis, full anticoagulation dosing is necessary; Infants, Children, and Adolescents: IV: 100 units/kg prior to ECMO cannulation followed by continuous IV heparin infusion to maintain the 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 (AHA [Giglia 2013])

Parenteral nutrition (PN) additive, venous access patency: Infants, Children, and Adolescents: 1 unit/mL (final heparin concentration in PN), both central and peripheral. The final concentration of heparin used for PN solutions may need to be decreased to 0.5 units/mL in small infants receiving larger PN volumes in order to avoid approaching therapeutic amounts (Corkins 2015).

Peripheral arterial catheters in situ: Infants and Children: Intra-arterial (via arterial catheter): Continuous infusion of heparin at a final concentration of 5 units/mL at 1 mL/hour (ACCP [Monagle 2012]; Butt 1987)

Thromboprophylaxis in CHD patients with systemic to pulmonary artery shunts (eg, Sano shunt, Blalock-Taussig shunt, central shunt) or central venous lines in certain CHD patients (eg, previous thrombosis or hypercoagulable states): Infants, Children, and Adolescents: Low Dose: Continuous IV infusion: 10 to 15 units/kg/hour (AHA [Giglia 2013])

Thrombosis, treatment:

Systemic heparinization:

Infants: IV: Initial loading dose: 75 units/kg over 10 minutes; then initial continuous maintenance infusion at: 28 units/kg/hour; adjust dose to maintain an anti-Xa activity of 0.35 to 0.7 units/mL or an aPTT range that correlates to this anti-Xa range or a protamine titration range of 0.2 to 0.4 units/mL (ACCP [Monagle 2012])

Children and Adolescents: IV: Initial loading dose: 75 units/kg over 10 minutes, then initial continuous maintenance infusion at: 20 units/kg/hour; adjust dose to maintain an anti-Xa activity of 0.35 to 0.7 units/mL or an aPTT range that correlates to this anti-Xa range or a protamine titration range of 0.2 to 0.4 units/mL (ACCP [Monagle 2012])

Note: Because of variation among hospitals with reagents (lot numbers) and corresponding control of aPTT values, individual institutions should establish unique, institution-specific nomograms based on current reagent. Due to extensive variability within reagents and anti-Xa levels with corresponding aPTTs, a specific nomogram has not been provided; refer to guidelines for a specific nomogram (ACCP [Monagle 2012]).

Systemic to pulmonary artery shunt thrombosis (eg, Sano shunt, Blalock-Taussig shunt, central shunt); treatment in CHD patients: Infants, Children, and Adolescents: IV: 50 to 100 units/kg, ongoing continuous infusion should be considered (AHA [Giglia 2013])

Administration

SubQ: Inject in subcutaneous tissue only (not muscle tissue). Injection sites should be rotated (usually left and right portions of the abdomen, above iliac crest).

IM: Do not administer IM due to pain, irritation, and hematoma formation.

Continuous IV infusion: Infuse via infusion pump. If preparing solution, mix thoroughly prior to administration.

Heparin lock: Inject via injection cap using positive pressure flushing technique. Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Central venous catheters: Must be flushed with heparin solution when newly inserted, daily (at the time of tubing change), after blood withdrawal or transfusion, and after an intermittent infusion through an injectable cap. A volume of at least 10 mL of blood should be removed and discarded from a heparinized line before blood samples are sent for coagulation testing.

Intravesical (off-label use): Various dosage regimens of heparin (20,000 to 50,000 units) alone or with alkalinized lidocaine (1% to 4%) have been instilled into the bladder.

Storage

Heparin solutions are colorless to slightly yellow. Minor color variations do not affect therapeutic efficacy. Heparin should be stored at room temperature. Protect from freezing and temperatures >40°C.

Stability at room temperature and refrigeration:

Prepared bag: 24 to 72 hours (specific to solution, concentration, and/or study conditions)

Premixed bag: After seal is broken, 4 days.

Out of overwrap stability: 30 days.

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the adverse/toxic effect of Heparin. Specifically, the risk for bleeding/bruising may be increased. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Consider therapy modification

Aliskiren: Heparin may enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Angiotensin II Receptor Blockers: Heparin may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Heparin may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy

Antithrombin: May enhance the anticoagulant effect of Heparin. Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Aspirin: May enhance the anticoagulant effect of Heparin. Monitor therapy

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Corticorelin: Heparin may enhance the adverse/toxic effect of Corticorelin. Significant hypotension and bradycardia have been previously attributed to this combination. Avoid combination

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Consider therapy modification

Drospirenone: Heparin may enhance the hyperkalemic effect of Drospirenone. Monitor therapy

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination

Eplerenone: Heparin may enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification

Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Management: Avoid such combinations when possible. If used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds). Consider therapy modification

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

Nitroglycerin: May diminish the anticoagulant effect of Heparin. Nitroglycerin may decrease the serum concentration of Heparin. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Consider therapy modification

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Oritavancin: May diminish the therapeutic effect of Heparin. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor IV heparin effectiveness, which could lead to incorrect decisions to decrease heparin doses. Avoid combination

Palifermin: Heparin may increase the serum concentration of Palifermin. Management: If heparin is used to maintain an intravenous line, rinse the line with saline prior to and after palifermin administration. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Pentoxifylline: May enhance the anticoagulant effect of Heparin. Monitor therapy

Potassium Salts: Heparin may enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Potassium-Sparing Diuretics: Heparin may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Streptokinase: May enhance the anticoagulant effect of Heparin. Avoid combination

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Telavancin: May diminish the therapeutic effect of Heparin. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor IV heparin effectiveness, which could lead to incorrect decisions to decrease heparin doses. Avoid combination

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tobacco (Smoked): May decrease the serum concentration of Heparin. Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination

Test Interactions

Increased thyroxine (competitive protein binding methods); increased PT

Aprotinin significantly increases aPTT and celite Activated Clotting Time (ACT) which may not reflect the actual degree of anticoagulation by heparin. Kaolin-based ACTs are not affected by aprotinin to the same degree as celite ACTs. While institutional protocols may vary, a minimal celite ACT of 750 seconds or kaolin-ACT of 480 seconds is recommended in the presence of aprotinin. Consult the manufacturer’s information on specific ACT test interpretation in the presence of aprotinin.

Adverse Reactions

Note: Frequency not defined. Thrombocytopenia has been reported to occur at an incidence between 0% and 30%. It is often of no clinical significance. However, immunologically mediated heparin-induced thrombocytopenia (HIT) has been estimated to occur in 1% to 2% of patients, and is marked by a progressive fall in platelet counts and, in some cases, thromboembolic complications (skin necrosis, pulmonary embolism, gangrene of the extremities, cerebrovascular accident, or myocardial infarction).

Cardiovascular: Chest pain, shock (including hemorrhagic shock), thrombosis, vasospasm (allergic; possibly related to thrombosis)

Central nervous system: Chills, dysesthesia (feet), headache, peripheral neuropathy

Dermatologic: Dermal ulcer (rarely reported with deep subcutaneous injections; intramuscular injection [not recommended] is associated with a higher incidence of this effect), eczema, erythematous plaques (case reports), localized erythema (rarely reported with deep subcutaneous injections; intramuscular injection [not recommended] is associated with a higher incidence of this effect), skin necrosis, transient alopecia (delayed), urticaria

Endocrine & metabolic: Adrenal hemorrhage, hyperkalemia (suppression of aldosterone synthesis), hyperlipidemia (rebound; on discontinuation), ovarian hemorrhage

Gastrointestinal: Constipation, hematemesis, melena, nausea, vomiting

Genitourinary: Erectile dysfunction (frequent or persistent erection), hematuria

Hematologic & oncologic: Bruise (unexplained), gingival hemorrhage, hematoma (rarely reported with deep subcutaneous injections; intramuscular injection [not recommended] is associated with a higher incidence of this effect), hemorrhage, pulmonary hemorrhage, purpura, retroperitoneal hemorrhage, thrombocytopenia (see note)

Hepatic: Increased liver enzymes

Hypersensitivity: Anaphylactoid reaction, hypersensitivity reaction

Local: Local irritation, local pain (rarely reported with deep subcutaneous injections; intramuscular injection [not recommended] is associated with a high incidence of these effects)

Neuromuscular & skeletal: Osteoporosis (chronic therapy effect)

Ophthalmic: Allergic conjunctivitis, lacrimation

Respiratory: Asthma, bronchospasm (case reports), epistaxis, hemoptysis, rhinitis

Miscellaneous: Drug tolerance, fever

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: May occur, including fatal events. Use with caution in patients with an increased risk of bleeding, including subacute bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; continuous GI tube drainage; severe uncontrolled hypertension; history of hemorrhagic stroke; use shortly after brain, spinal, or ophthalmologic surgery or other invasive procedures including spinal tap or spinal anesthesia; concomitant treatment with platelet inhibitors; recent GI bleeding; impaired hemostasis; thrombocytopenia or platelet defects; patients with hereditary antithrombin deficiency receiving concurrent antithrombin replacement therapy; severe liver disease; hypertensive or diabetic retinopathy; renal failure; or in patients (especially women) >60 years of age. Monitor patient closely for signs or symptoms of bleeding. Discontinue if bleeding occurs; severe hemorrhage or overdosage may require protamine (consult Protamine monograph for dosing recommendations).

• Heparin resistance: 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, elevations in factor VIII and/or fibrinogen; frequently encountered in patients with fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, MI, cancer, and in postsurgical patients; measurement of anticoagulant effects using antifactor Xa levels may be of benefit.

• Hyperkalemia: Monitor for hyperkalemia; can cause hyperkalemia by suppressing aldosterone production.

• Hypersensitivity reactions: May occur; only in life-threatening situations when use of an alternative anticoagulant is not possible should heparin be cautiously used in patients with a documented hypersensitivity reaction. Some products are derived from animal tissue and may be contraindicated in patients with animal allergies (ie, pork); consult individual prescribing information.

• Osteoporosis: May occur with prolonged use (>6 months) due to a reduction in bone mineral density.

• Thrombocytopenia: May occur. Heparin-induced thrombocytopenia (HIT), a serious antibody-mediated reaction resulting from irreversible aggregation of platelets, may also occur. Patients who develop HIT may be at risk of developing a new thrombus (heparin-induced thrombocytopenia and thrombosis [HITT]). Monitor platelets closely; discontinue therapy and consider alternatives if platelets are <100,000/mm3 and/or thrombosis develops. HIT or HITT may be delayed and can occur up to several weeks after discontinuation of heparin. Use with extreme caution (for a limited duration) or avoid in patients with history of HIT, especially if administered within 100 days of HIT episode (Dager 2007; Warkentin 2001).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant drug-drug interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: 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 in these patients. May require lower doses.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol as a preservative. In neonates, large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome"); the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. Use in neonates, infants, or pregnant or nursing mothers is contraindicated by some manufacturers; the use of preservative-free heparin is, therefore, recommended in these populations.

• Sulfites: Some preparations contain sulfite which may cause allergic reactions.

Other warnings/precautions:

• Fatal medications errors: Many concentrations of heparin are available ranging from 1 unit/mL to 20,000 units/mL. Clinicians must carefully examine each prefilled syringe or vial prior to use ensuring that the correct concentration is chosen; fatal hemorrhages have occurred related to heparin overdose especially in pediatric patients.

Monitoring Parameters

Hemoglobin, hematocrit, signs of bleeding; fecal occult blood test; aPTT (or antifactor Xa activity levels) or ACT depending upon indication

Platelet counts should be routinely monitored (eg, every 2 to 3 days on days 4 to 14 of heparin therapy) when the risk of HIT is >1% (eg, receiving therapeutic dose heparin, postoperative antithrombotic prophylaxis), if the patient has received heparin or low molecular weight heparin (eg, enoxaparin) within the past 100 days, if pre-exposure history is uncertain, or if anaphylactoid reaction to heparin occurs. When the risk of HIT is <1% (eg, medical/obstetrical patients receiving heparin flushes), routine platelet count monitoring is not recommended (Guyatt 2012).

For intermittent IV injections, aPTT is measured 3.5 to 4 hours after IV injection.

Note: Continuous IV infusion is preferred over IV intermittent injections. For full-dose heparin (ie, nonlow-dose), the dose should be titrated to an aPTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 units/mL of anti-Xa activity or 0.2 to 0.4 unit/mL by protamine titration. Because of variation among hospitals in the control aPTT values, nomograms should be established at each institution, designed to achieve aPTT values in the target range. (ACCP [Garcia 2012]; ACCP [You 2012]; Bates 2001; Hirsh 1994; Vandiver 2012). Measurements should be made prior to heparin therapy, 6 hours (pediatric: 4 hours) after initiation, and 6 hours (pediatric: 4 hours) after any dosage change, and should be used to adjust the heparin infusion until the aPTT exhibits a therapeutic level. When two consecutive aPTT values are therapeutic, subsequent measurements may be made every 24 hours, and if necessary, dose adjustment carried out. In addition, a significant change in the patient's clinical condition (eg, recurrent ischemia, bleeding, hypotension) should prompt an immediate aPTT determination, followed by dose adjustment if necessary. In general, may increase or decrease infusion by 2 to 4 units/kg/hour dependent upon aPTT.

Pregnancy Considerations

Heparin does not cross the placenta (ESC [Regitz-Zagrosek 2018]).

Heparin may be used for anticoagulation in pregnancy (ACOG 196 2018). Due to a better safety profile and ease of administration, the use of low molecular weight heparin (LMWH) is generally preferred over heparin (unfractionated heparin [UFH]) in pregnancy (ACOG 196 2018; Bates 2018; ESC [Regitz-Zagrosek 2018]). Anticoagulant therapy for the prevention and treatment of thromboembolism in pregnant females can be discontinued prior to induction of labor or a planned cesarean delivery (Bates 2018) or LMWH can be converted to UFH in higher risk women (ESC [Regitz-Zagrosek 2018]). UFH or LMWH may be used in pregnant patients with mechanical heart valves (ESC [Regitz-Zagrosek 2018]; Nishimura 2014).

Some products contain benzyl alcohol as a preservative; their use in pregnant females is contraindicated by some manufacturers; use of a preservative-free formulation is recommended.

Patient Education

What is this drug used for?

• It is used to thin the blood so that clots will not form.

• It is used to treat blood clots.

• It is used to keep blood from clotting in catheters.

• It may be given to you for other reasons. Talk with the doctor.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes.

• DVT like edema, warmth, numbness, change in color, or pain in the extremities.

• Severe dizziness

• Passing out

• Confusion

• Severe headache

• Coughing up blood

• Groin or pelvic pain and swelling

• Chills

• Chest pain

• Back pain

• Shortness of breath

• Injection site skin discoloration or skin breakdown

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

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