Hot topics in coagulation testing: Important considerations for testing children for bleeding/thrombotic disorders

The accurate use and interpretation of diagnostic investigations are essential for safe and effective patient care. Appropriate application and interpretation of coagulation testing can be challenging, and many controversies exist relating to the standardization of testing procedures, the application of relevant tests to different patient populations and the interpretation of test results. We present a list of the most prominent controversies in coagulation testing and have selected three specific examples (age-appropriate reference ranges, therapeutic anticoagulation monitoring and tests of thrombin generation) for closer discussion, highlighting examples with a paediatric framework. We discuss the limitations of discrete age-partitioned reference intervals, given the established principle of developmental haemostasis; the difficulties in establishing normative data across different laboratories; important pre-analytical variables affecting coagulation testing; the challenges in interpreting APTT and anti-Xa assays for monitoring unfractionated heparin therapy in different clinical situations; and the limitations in interpreting tests of thrombin generation due to current available thrombin-specific substrates and the complicating factor of variable alpha2-macroglobulin levels. These controversies are demonstrated using paediatric examples, but raise important implications for coagulation testing in patients of all ages and highlight the pressing need for further research in these areas.