HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Eby, C. Search for Related Content PubMed PubMed Citation Articles by Eby, C. Related Collections Laboratory Management Hemostasis and Thrombosis

Standardization of APTT Reagents for Heparin Therapy Monitoring: Urgent or Fading Priority?

Department of Pathology, Saint Louis University Health Sciences Center, 3635 Vista Ave. at Grand Blvd., St. Louis, MO 63110, ebycs@sluh_his.sluh.edu

Tremendous improvements have been made in the outcomes of patients with acute venous thromboembolic events (VTE) since Murray et al. successfully administered heparin to postsurgery patients in 1937 (1). Advances include accurate methods for diagnosis of deep vein thromboses (DVT) and pulmonary emboli (PE); effective regimens for initial and long-term anticoagulation; and wide acceptance of a system for standardization of thromboplastin sensitivities to the anticoagulant effects of warfarin (International Normalized Ratio; INR). In this issue of Clinical Chemistry, van den Besselaar et al. (2) address an unresolved aspect of anticoagulation therapy: standardization of activated partial thromboplastin time (APTT) reagents for monitoring heparin therapy.

Heparin is a glycosaminoglycan extracted from mast cells of porcine intestinal mucosa or bovine lung. It is composed of long chains of alternating D-glucuronic acid and N-acetyl-D-glucosamine sugar residues, which undergo a series of chemical modifications, primarily sulfation, leading to unique pentasaccharide sequences that serve as a binding site for antithrombin III (AT III) (3). The anticoagulant effect of heparin is mediated through this interaction, which markedly accelerates the rate of AT III inhibition of thrombin (factor IIa) and factor Xa. Heparin polysaccharides are heterogeneous in length and anticoagulation activity and range in mass from 5000 to 30 000 kDa. Commercial preparations are calibrated in USP units, 1 unit being defined as the quantity that prevents 1.0 mL of citrated sheep plasma from clotting for 1 h after the addition of 0.2 mL of 10 g/L CaCl₂ (3).

Low-molecular-weight heparins (LMWH) are produced from unfractionated heparin to yield smaller polysaccharides with average molecular masses of 4000–5000 kDa. These shorter molecules lose the ability to accelerate AT III inhibition of thrombin but retain the ability to catalyze factor Xa inhibition. Decreased in vivo protein binding . . . [Full Text of this Article]

References

The following articles in journals at HighWire Press have cited this article:

				H. Gorki, V. Malinovski, and R. D.L. Stanbridge The antiphospholipid syndrome and heart valve surgery Eur. J. Cardiothorac. Surg., February 1, 2008; 33(2): 168 - 181. [Abstract] [Full Text] [PDF]