Therapeutic monitoring of unfractionated heparin – trials and tribulations

Abstract

Heparin is one of the oldest biological medicines with an established role in prevention and treatment of arterial and venous thromboembolism. Published therapeutic ranges for unfractionated heparin (UFH) mostly precede the large increase in the number of activated partial thromboplastin time (APTT) reagent/instrument combinations that now show wide variability. Areas covered: This paper explores the use of UFH, the development of heparin therapeutic ranges (HTRs), and the strengths and limitations of the methods used to monitor heparin's anticoagulant effect. Expert commentary: Despite longstanding use of UFH for management of thromboembolic conditions, the optimal test for monitoring UFH remains undetermined. Although used extensively for monitoring UFH, routine APTT-derived HTRs are based on limited science that may have little relevance to current laboratory practice. Anti-FXa levels may provide better and more reliable HTRs; however, even these levels show considerable inter-laboratory variation, and there are insufficient clinical studies proving improved clinical efficacy. Alternative tests for monitoring UFH reported over time have not been proven effective nor feasible, secondary to technical or cost issues, or lack of general adoption. Thus, despite limited evidence of clinical utility, an uncomfortable marriage of convenience represented by heparin laboratory monitoring is unlikely to be terminated in the immediate future.

Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

“…The anticoagulant heparin is given to patients for many reasons, including anticoagulant therapy to treat or prevent thrombosis, to maintain patency of circuits during operative procedures (e.g., cardiac surgery), and to maintain patency of central lines . Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet‐factor 4‐heparin (“anti‐PF4‐heparin”).…”

An update on the Immunopathology of Immune thrombocytopenia (ITP)

“…The most common approach to establishing a TR for UH by APTT is to perform correlation studies against an anti-FXa assay and to identify the APTT range representing an UH level of 0.3-0.7 U/mL by anti-FXa, 1 with this anti-Xa range representing a common TR for UH. 2 There are many common pitfalls with this approach, including high variability in APTT according to anti-FXa according to individual variation, especially considering that anti-FXa testing represents a more discrete analyte compared to the global assay of APTT. Several additional confounders, including FXII deficiency and lupus anticoagulants, both not uncommon in patients on UH therapy, as well as many undefinable events, lead to poor correlation between APTT and anti-FXa.…”

Preanalytical issues that may cause misdiagnosis in haemophilia and von Willebrand disease

“…Heparin anticoagulant, for example, is used ubiquitously in hospital settings, not only as anticoagulant therapy for treatment/prevention of thrombosis, but also to maintain patency of lines, during cardiac surgery or haemodialysis, and in heparinized needles for blood‐gas collections . Depending on the level of heparin “contaminating” any plasma sample, raised coagulation tests (eg APTT) may lead to investigation of factor “deficiency” and false identification thereof, as noted previously.…”