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Antithrombin

Medically reviewed by Drugs.com. Last updated on Jul 29, 2020.

Pronunciation

(an tee THROM bin)

Index Terms

  • Antithrombin Alfa
  • Antithrombin III
  • AT
  • AT-III
  • ATIII
  • hpAT
  • rhAT
  • rhATIII

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [human, preservative free]:

Thrombate III: 500 units, 1000 units [contains heparin; exact potency labeled on each vial]

Brand Names: U.S.

  • Thrombate III

Pharmacologic Category

  • Anticoagulant
  • Blood Product Derivative

Pharmacology

Antithrombin is the primary physiologic inhibitor of in vivo coagulation. It is an alpha2-globulin. Its principal actions are the inactivation of thrombin, plasmin, and other active serine proteases of coagulation, including factors IXa, Xa, XIa, and XIIa. The inactivation of proteases is a major step in the normal clotting process. The strong activation of clotting enzymes at the site of every bleeding injury facilitates fibrin formation and maintains normal hemostasis. Thrombosis in the circulation would be caused by active serine proteases if they were not inhibited by antithrombin after the localized clotting process (Schwartz, 1989).

In patients with hereditary antithrombin (AT) deficiency, spontaneous thrombosis may occur due to decreased AT concentrations; therapy with human or recombinant AT restores functional AT activity.

Half-Life Elimination

Plasma derived (Thrombate III): Biologic: 2.5 days (immunologic assay); 3.8 days (functional AT assay). Half-life may be decreased following surgery, with hemorrhage, acute thrombosis, and/or during heparin administration.

Use: Labeled Indications

Hereditary antithrombin deficiency: Thrombate III: Treatment and prevention of thromboembolism and prevention of perioperative and peripartum thromboembolism in patients with hereditary antithrombin deficiency.

Off Label Uses

Intraoperative heparin resistance during cardiopulmonary bypass

Data from a limited number of patients suggest that antithrombin may be beneficial to improve heparinization during cardiopulmonary bypass in patients with difficulty achieving therapeutic activated clotting time values [Lemmer 2002].

Contraindications

Thrombate III: There are no contraindications listed in manufacturer's labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to antithrombin, other anticoagulants, or any component of the formulation.

Dosing: Adult

Hereditary antithrombin deficiency:

Thrombate III: Prophylaxis of thrombosis during surgical or obstetrical procedures or treatment of thromboembolism:

IV:

Initial loading dose: Dosing is individualized based on pretherapy antithrombin (AT) levels. The initial dose should raise AT levels to 120% and may be calculated based on the following formula:

[(desired AT level % - baseline AT level %) x body weight (kg)] divided by 1.4 = units of antithrombin required

For example, if a 70 kg adult patient had a baseline AT level of 57%, the initial dose would be:

[(120% - 57%) x 70] divided by 1.4 = 3150 units

Maintenance dose: In general, subsequent dosing should be targeted to keep levels between 80% to 120%, which may be achieved by administering 60% of the initial loading dose every 24 hours. Adjustments may be made by adjusting dose or interval. Maintain level within normal range for 2 to 8 days depending on type of procedure/situation.

Intraoperative heparin resistance during cardiopulmonary bypass (off-label use):

Thrombate III: IV: Initial: 500 units once (dose can be rounded to the nearest vial size); a repeat dose of 500 units may be considered if activated clotting time remains subtherapeutic after the initial dose (Lemmer 2002).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Thrombate III: Bring drug and diluent to room temperature prior to reconstitution. Reconstitute with sterile water for injection. Do not shake; swirl to mix to avoid foaming. Filter through sterile filter needle provided prior to administration.

Administration

IV: Thrombate III: Infuse over 10 to 20 minutes.

Dietary Considerations

Some products may contain sodium.

Storage

Thrombate III: Store intact vials at temperatures not exceeding 25°C (77°F); avoid freezing. Administer within 3 hours after reconstitution. Do not refrigerate reconstituted product.

Drug Interactions

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

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. 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

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

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. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

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

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

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

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

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

Heparins (Low Molecular Weight): Antithrombin may enhance the anticoagulant effect of Heparins (Low Molecular Weight). Monitor therapy

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

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. 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

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

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

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

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

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

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

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

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

Adverse Reactions

1% to 10%:

Cardiovascular: Chest pain (≤2%)

Central nervous system: Dizziness (2%)

Gastrointestinal: Liver enzyme abnormalities (≤2%)

Genitourinary: Hematuria (≤2%)

Hematologic & oncologic: Hemorrhage (≥5%), hematoma (≤2%)

Local: Infusion site reaction (≥5%)

Neuromuscular & skeletal: Hemarthrosis (≤2%)

<1%, postmarketing, and/or case reports: Blurred vision, chest tightness, chills, dizziness, dyspnea, fever, gastrointestinal fullness, muscle cramps, nausea, unpleasant taste, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions, including severe hypersensitivity reactions (eg, anaphylaxis), may occur; monitor closely during infusions. If hypersensitivity symptoms occur, discontinue immediately and institute supportive emergency care.

• Infections: Thrombate III: Thrombate III is AT collected from pooled human plasma (hpAT). A product of human plasma, it may potentially contain infectious agents which could transmit disease, including the Creutzfeldt-Jakob Disease (CJD) agent; screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces this risk. Infections suspected to be transmitted by this product should be reported to the manufacturer.

Other warnings/precautions:

• Pharmacokinetic differences: Half-life and clearance differ significantly (~7 to 9 times) between the plasma-derived and the recombinant-derived product.

Monitoring Parameters

Hereditary antithrombin deficiency:

Thrombate III: Initially, monitor antithrombin (AT) at baseline, 20 minutes postinfusion (peak), 12 hours postinfusion, then preceding next infusion (trough level). Measure peak and trough AT levels with each subsequent dose until predictable levels achieved (between 80% and 120%). Some situations (eg, following surgery, hemorrhage or acute thrombosis, concurrent IV heparin administration), may require more frequent AT monitoring.

AT concentrations in neonates of parents with hereditary AT deficiency should be measured immediately after birth.

Intraoperative heparin resistance during cardiopulmonary bypass (off-label use):

Due to laboratory turn-around times, routine monitoring of AT levels before or after Thrombate III administration is not feasible in the intraoperative setting. Therefore, therapeutic response should be monitored with activated clotting time (Lemmer 2002).

Pregnancy Considerations

The risk of thromboembolic events such as venous thromboembolism (VTE) is increased in patients with hereditary antithrombin (AT) deficiency. Pregnancy-induced physiologic changes also increase this risk; risk is dependent upon maternal antithrombin levels and personal or family history of thromboembolism (ACOG 197 2018). Thrombate III is approved for use in pregnant women with hereditary AT deficiency to replace endogenous antithrombin and reduce the risk of peripartum thromboembolism. Antithrombin replacement can be used in pregnant patients with hereditary AT deficiency in high-risk settings (eg, childbirth, miscarriage, surgery) when other anticoagulant therapy (eg, low molecular weight heparin [LMWH]) is withheld or as adjunctive therapy to LMWH in pregnant women at high risk for VTE (Bauer 2016; Ilonczai 2015; James 2017; Rogenhofer 2014).

Patient Education

What is this drug used for?

• It is used to treat antithrombin deficiency.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Cramps

• Change in taste

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Chest pain

• Severe dizziness

• Passing out

• Severe nausea

• Vomiting

• Burning or numbness feeling

• Restlessness

• Shortness of breath

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.