Pharmacology and clinical applications of human recombinant antithrombin.
BACKGROUND
Antithrombin therapy (AT) has been tested in various medical applications. With advances in genetics and biotechnology, large-scale production of human recombinant antithrombin (rhAT) is now feasible. The prospect of administering a recombinant protein rather than a pooled blood component, has rekindled interest in antithrombin therapy. However, many known properties of human pooled antithrombin (hpAT) still need to be investigated and established for rhAT.


METHODS
The manufacture and clinical pharmacology of antithrombin. The literature, evidence and our own views about the future of this drug and its potential clinical applications.


RESULTS
The reader will appreciate the biological rationale underpinning antithrombin administration in various clinical settings. The potential benefits and harms of the intervention are addressed. Novel future applications of recombinant antithrombin are broached.


CONCLUSIONS
rhAT has been approved for its use in congenital antithrombin deficiency. rhAT has also been used off-label to treat heparin-resistance in cardiac surgery and sepsis. It is a promising adjuvant for immunosuppression in organ transplantation, and may have role as an anti-angiogenic, anti-tumor and anti-viral agent. rhAT has clear safety advantages over phAT, such as the avoidance of infection transmission.
Washington University School of Medicine, Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, 660 South Euclid, Campus Box 8054, St Louis, MO 63110-1093, USA. paln@wustl.edu
Nirvik
N
Pal
Miklos D
MD
Kertai
Anand
A
Lakshminarasimhachar
Michael S
MS
Avidan
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D020152:Antithrombin III Deficiency / Q000188:drug therapy; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007430:Intraoperative Care; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy
D020533:Angiogenesis Inhibitors; D000925:Anticoagulants; D000991:Antithrombins; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins