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Medication

Medication Summary

Plasma-derived antithrombin (AT) is approved by the US Food and Drug Administration (FDA) for use in patients with AT deficiency. In patients with congenital AT deficiency, replacement/prophylaxis is recommended in the following settings:

Before or following major surgery
During bed rest for longer than 24 hours, because of the increased risk of thrombosis
For thrombosis during pregnancy, to allow heparin to be effective
For acute deep venous thrombosis or pulmonary embolism.

Recombinant human AT (Atryn) is approved by the FDA for the prevention of perioperative and peripartum thromboembolism in patients with congenital AT deficiency. It is not approved for the treatment of thromboembolic events. Recombinant human AT is also approved for use in Europe for the perioperative prophylaxis of venous thromboembolism in patients with congenital AT deficiency.

Class Summary

For antithrombin replacement, the clinical goal is to maintain the level of antithrombin activity at 80% or greater for full effect. Serial monitoring of levels is necessary to ensure an adequate level. The anticoagulant effect of heparin is enhanced by antithrombin; thus, for heparinized patients, monitoring of the aPTT is necessary to determine the need to reduce the heparin dosage when heparin is being concomitantly administered with antithrombin.

Dosage calculation guidelines

The required dose of AT concentrate = (% desired – % baseline) × body weight (kg) divided by 1.4.

This calculation is based on an expected rise of 1.4% with 1 IU/kg given intravenously. Recoveries vary from patient to patient and are also affected by the underlying disease. Therefore, baseline and 20-minute post-infusion samples should be tested for antithrombin activity to determine the initial response to a dose. Subsequently, pre-dose trough level and immediate post-dose values provide trough and peak values to help in further dosing. Maintaining antithrombin activity levels of approximately 80% normal serum values are suggested. Surgery, bleeding, and active thrombosis affect the half-life of this product, but the duration of effect in normal volunteers was 22 hours. Following the initial loading dose, antithrombin activity levels rise to ~120%, and approximately 60% of that dose should be administered every 24 hours as a maintenance dose.

Antithrombin III, human (ATnativ, Thrombate III)

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A serine protease inhibitor (an alpha2-globulin) that inactivates thrombin, plasmin, and other serine proteases of coagulation, including factors IXa, Xa, XIa, XIIa, and VIIa. Made from pooled human plasma and is heat treated. Do not refrigerate after reconstitution, and administer within 3 h of reconstitution. Although there is a theoretical risk of infectious disease transmission because this product is derived from human plasma, there have been no reported cases to date.

Antithrombin, recombinant (Atryn)

View full drug information

Antithrombin (AT) regulates hemostasis by inhibiting thrombin and factor Xa, key proteases for blood coagulation. Indicated for prevention of perioperative and peripartum thromboembolic events in patients with hereditary AT deficiency. Not indicated for treatment of thromboembolic events.

Class Summary

Use inhibitors of fibrinolysis together with FFP replacement for minor surgical procedures (eg, dental extractions, sinus surgery) so that they can be accomplished on an outpatient basis with the use of a single dose of product.

Concern about the possible relationship to acute thrombotic events remains, although a causal relationship is being questioned because the underlying disease state determines the site and extent of thrombosis.

Pooled plasma, solvent-detergent treated (PLAS+SD)

Solvent-detergent (SD) treatment of pooled human plasma removes lipid-enveloped viruses, making this product safer than untreated FFP. SD treatment, however, does not remove all viruses from plasma. Efficacy and safety has been proven in the treatment of several coagulopathies. Per the package insert from the American Red Cross, the half-life of the coagulation factors in recipients of this product were similar to normal values at the time they were measured.

If available, SD-treated plasma can be used in patients with alpha2-antiplasmin deficiency, because no concentrate is available to treat this coagulation factor deficiency. As with any bleeding disorder, serial measurement of the specific coagulation factor in question is essential to assure hemostatic adequacy of levels. On average, 1 U of SD plasma raises factor levels by ~2-3%, whereas 4-6 U raises factor levels by ~8-18% in a 70-kg person. These numbers do not specifically apply to alpha2-antiplasmin and are being provided only as a general guide.

Serial monitoring of required alpha2-antiplasmin levels is necessary to follow these patients. This product should be stored at -18°C or colder, and thawed at 30-37°C in a water bath with very gentle shaking; once thawed, keep at room temperature and use as soon as possible, preferably within 24 h. Do not store thawed material in the cold.

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Media Gallery

Antithrombin (AT) neutralizes the enzyme (IIa) by forming a 1:1 stoichiometric complex (AT:IIa) between the arginine-serine sites of the 2 proteins. Binding of heparin to lysyl residues on AT results in a conformational change in AT, which makes it more available to bind thrombin (IIa), IXa, and Xa, thus markedly accelerating the rate of enzyme-inhibitor complex formation. AT also neutralizes XIa and XIIa.
Cell surface–directed hemostasis (image adapted from Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001). Initially, a small amount of thrombin is generated on the surface of the tissue factor–bearing (TF-bearing) cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation.
Antithrombin sites of action.

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Author

Drew H Barnes, MD Fellow Physician, Hospice and Palliative Medicine, The Ohio State University Wexner Medical Center

Drew H Barnes, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

David Aboulafia, MD Medical Director, Bailey-Boushay House, Clinical Professor, Department of Medicine, Division of Hematology, Attending Physician, Section of Hematology/Oncology, Virginia Mason Clinic; Investigator, Virginia Mason Community Clinic Oncology Program/SWOG

David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, AMDA - The Society for Post-Acute and Long-Term Care Medicine, American Society of Hematology, Infectious Diseases Society of America, Phi Beta Kappa

Disclosure: Nothing to disclose.

Bryan A Mitton, MD, PhD Clinical Instructor, Division of Pediatric Hematology-Oncology, Department of Pediatrics, Stanford University School of Medicine

Disclosure: Nothing to disclose.

Angela Steineck, MD, MS Assistant Professor of Pediatric Oncology, MACC Fund Center for Cancer and Blood Disorders - Children's Wisconsin, Medical College of Wisconsin

Angela Steineck, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Sara J Grethlein, MD Associate Dean for Undergraduate Medical Education, Indiana University School of Medicine

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Arun Rajan, MD Clinical Fellow, Medical Oncology Branch, National Cancer Institute/National Institutes of Health

Arun Rajan, MD is a member of the following medical societies: American Medical Association and American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Antithrombin Deficiency Medication

Medication Summary

Antithrombin Supplements

Class Summary

Antithrombin III, human (ATnativ, Thrombate III)

Antithrombin III, human (ATnativ, Thrombate III)

Antithrombin, recombinant (Atryn)

Antithrombin, recombinant (Atryn)

Antihemophilic Agents

Class Summary

Pooled plasma, solvent-detergent treated (PLAS+SD)

Antithrombin Deficiency Medication

Medication Summary

Antithrombin Supplements

Class Summary

Antithrombin III, human (ATnativ, Thrombate III)

Antithrombin III, human (ATnativ, Thrombate III)

Antithrombin, recombinant (Atryn)

Antithrombin, recombinant (Atryn)

Antihemophilic Agents

Class Summary

Pooled plasma, solvent-detergent treated (PLAS+SD)

References

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