Antithrombin Deficiency Medication

Updated: Oct 21, 2015
  • Author: Bryan A Mitton, MD, PhD; Chief Editor: Perumal Thiagarajan, MD  more...
  • Print
Medication

Medication Summary

Plasma-derived antithrombin is approved by the US Food and Drug Administration (FDA) for use in patients with antithrombin (AT) deficiency. In patients with congenital deficiency of antithrombin III, replacement/prophylaxis is recommended (1) before or following major surgery, (2) during bed rest for longer than 24 hours (because of the increased risk of thrombosis), (3) for thrombosis during pregnancy, to allow heparin to be effective, and (4) for acute deep venous thrombosis or pulmonary embolism.

Recombinant human antithrombin (Atryn) was approved by the FDA in early 2009 for the prevention of perioperative and peripartum thromboembolism in patients with congenital antithrombin deficiency. It is not approved for treatment of thromboembolic events. Recombinant human antithrombin is also approved for use in Europe for the perioperative prophylaxis of venous thromboembolism in patients with congenital AT deficiency.

The reader is encouraged to review the FDA package insert with each product that is used for therapy.

Next:

Antithrombin Supplements

Class Summary

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)

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)

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.

Previous
Next:

Antihemophilic Agents

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)

See details of discussion under Medical Care. 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.

Previous