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Antithrombin Deficiency Affects Heparin Assays

Another important issue addressed by Dr. James Quesenberry, St. Luke’s Laboratory, Sioux City, Iowa. His message: I understood from early on that antithrombin (AT, antithrombin III, ATIII) deficient patients can’t be assayed for unfractionated heparin using the Stago chromogenic anti-Xa heparin assay.  I thought this was an all-or-none issue, only a big deal in congenital severe AT  deficient folks. Today I learned that clients need to locally establish the AT level below which they believe the assay in their hands at their locale to be not accurate.  This seems highly impractical to do, particularly in the non-university small to medium sized community hospital setting.  We were mainly curious as to how other Stago users deal with this.

Hello, Dr. Quesenberry, and thank you. I brought your question to Dr. Paul Riley, Stago’s Scientific Business Development Manager, who has provided assistance. The question raises several issues…

  • Acquired or inherited AT deficiency, though rare may affect partial thromboplastin time (PTT, activated partial thromboplastin time, APTT)-based heparin monitoring. Depending on the patient’s factor levels or other issues in critically ill patients, the PTT may fail to prolong or the prolongation may be very significant as heparin dosage is raised.  Though heparin’s anticoagulant effect relies on its upregulation of AT ‘s “serine protease inhibitor” property. The phenomenon has been named “heparin resistance.”
  • Some chromogenic anti-Xa heparin assay manufacturer’s kits do not include AT. Manufacturers may offer alternative kits which include AT supplementation, however according to CAP survey results, a minority of labs choose the supplemented AT option.
  • “Non-AT” kits are preferred because AT sensitivity (heparin resistance) provides clinicians with an accurate picture of the anticoagulation the patient is receiving. If the AT is deficient, the heparin is not working and the patient may require AT supplementation or alternative anticoagulation. This picture would be masked if the lab was using an AT-supplemented anti-Xa (Gehrie E, Laposata M. Test of the Month: The chromogenic anti-factor Xa assay. Am J Hematol 2012; 87: 194–7).
  • It is not practical, nor necessary, to measure AT in all heparin patient specimens, though it may be helpful to establish the patient AT level at which the anti-Xa assay is sensitive to lower than normal levels. Subsequently, it is only necessary to check the AT in patients whose clinical circumstances and anti-Xa results hint at AT deficiency or “heparin resistance.” In these cases, the AT assay would help direct therapy.  Critically ill patients, including those with AT deficiency may also have other interferences caused by their respective clinical conditions (e.g. hemolysis) which could affect the anti-Xa results.
  • For pediatric populations, only a “non-AT” assay is recommended in the ISTH guideline pulbished in Ignjatovic V, Kenet G, Monagle P; Perinatal and Paediatric Haemostasis Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Developmental hemostasis: recommendations for laboratories reporting pediatric samples. J Thromb Haemost 2012; 10: 298–300.

I hope this information is helpful, and I would be happy to get posts from other anti-Xa kit users.

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