Laboratory Diagnostics for Thrombosis and Hemostasis Testing—Part IV

This is the fourth themed issue of Seminars in Thrombosis and Hemostasis (STH) focused on laboratory diagnostics. We are pleased to include two in-depth reviews covering the performance of D-dimer assays in clinical laboratories, as summarized by two external quality assessment (EQA) programs serving different parts of the world.[1] [2] D-dimer testing is non-standardized and non-harmonized but has important clinical uses for the exclusion of venous thromboembolism, diagnosis of disseminated intravascular coagulation, and provides prognostic information in serious illnesses, such as coronavirus disease 2019. Thus, the real-world performance of these assays has significant clinical implications.

A separate comprehensive review by Undas then covers an important topic in both clinical laboratories and research settings—laboratory testing for congenital and acquired fibrinogen disorders.[3] The review covers the use of common coagulation tests but also discusses molecular diagnosis and complex research assays that study fibrin formation and properties of fibrin clots.

In the subsequent review contributed by Jennings et al. on behalf of the EQATH organization, worldwide EQA results for thrombophilia assays are presented from testing performed on a plasma standard from the International Society on Thrombosis and Hemostasis Scientific and Standardization Committee.[4] The article provides proof of concept for pooling proficiency testing results from different EQA providers for analytes that are performed in only a few laboratories.

Next, Jin et al. present an original research study comparing anti-Xa and activated partial thromboplastin time (aPTT) results on hospitalized patients, with a particular focus on results that are discordant regarding the degree of heparinization and whether discordant values may predict clinical outcomes.[5]

Following this, Devreese provides an expert review on thrombosis in antiphospholipid syndrome, providing information on laboratory testing and how laboratory profiles can be used to risk-stratify patients and identify those at greatest risk of thrombotic events.[6]

Favaloro et al. then present an informative review on laboratory testing for ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity and also ADAMTS13 inhibitors.[7] In addition to discussion of use of ADAMTS13 testing to diagnose and manage thrombotic thrombocytopenic purpura (TTP), characterized by severe ADAMTS13 deficiency, the manuscript also discusses conditions with milder deficiencies and how disruption of the ADAMTS13–von Willebrand factor axis can create a prothrombotic milieu.

Favaloro and Arunachalam next present a review of practice for factor VIII inhibitor testing from Australasian and Asia-Pacific EQA data.[8] The data are reassuring since participating laboratories are mostly correct in their ability to identify the presence or absence of a factor inhibitor. However, the between-laboratory coefficients of variation on individual samples (affecting inhibitor titer) are rather large, highlighting opportunities for improved technical performance and standardization.

In a final review for this issue of STH, Ichinose provides detailed information about autoantibodies in autoimmune coagulation factor deficiencies.[9] For instance, these polyclonal antibodies can neutralize factor activity, accelerate factor clearance, or exhibit mixed features. The antibody characteristics have impacts on assays used to diagnose and monitor patients with these disorders.

Finally for this issue, in a Letter to the Editor, we learn about three patients with dysfibrinogenemia and unusual comorbid conditions.[10] The submission also includes information about important differences between von Clauss versus prothrombin time (PT) derived fibrinogen assays in patients with dysfibrinogenemia and potential use of the PT derived fibrinogen assay as a surrogate for fibrinogen antigen testing in this setting.

In summary, we are pleased to present this excellent issue of STH and hope readers value the content as much as we have during creation of the issue.

 

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Conflict of Interest

None declared.

• References

• 1 Favaloro EJ, Arunachalam S, Dean E. Variable performance of D-dimer testing by hemostasis laboratories: The Australasian/Asia-Pacific experience. Semin Thromb Hemost 2025; 51 (06) 629-640
• 2 Elbaz C, Hollestelle MJ, Meijer P, Liederman Z, Selby R. D-dimer-An international assessment of the quality of laboratory testing: Implications for D-dimer use in the real world. Semin Thromb Hemost 2025; 51 (06) 641-650
• 3 Undas A. Laboratory testing for fibrinogen disorders: From routine investigations to research studies. Semin Thromb Hemost 2025; 51 (06) 651-659
• 4 Jennings I, Meijer P, Arunachalam S. et al. Comparison of thrombophilia assay results for the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Plasma Standard from Different External Quality Assessment Providers-for the External Quality Assurance in Thrombosis and Haemostasis Group. Semin Thromb Hemost 2025; 51 (06) 660-666
• 5 Jin J, Gummidipundi S, Hsu J. et al. Discordant high activated partial thromboplastin time relative to anti-Xa values in hospitalized patients is an independent risk factor for increased 30-day mortality. Semin Thromb Hemost 2025; 51 (06) 667-675
• 6 Devreese KMJ. Thrombosis in antiphospholipid syndrome: Current perspectives and challenges in laboratory testing for antiphospholipid antibodies. Semin Thromb Hemost 2025; 51 (06) 676-686
• 7 Favaloro EJ, Pasalic L, Lippi G. Laboratory testing for ADAMTS13 for thrombotic thrombocytopenia purpura and beyond. Semin Thromb Hemost 2025; 51 (06) 687-697
• 8 Favaloro EJ, Arunachalam S. Factor inhibitor testing: An update from Australasia/Asia-Pacific. Semin Thromb Hemost 2025; 51 (06) 698-705
• 9 Ichinose A. Autoantibodies in autoimmune coagulation factor deficiencies: A review of inhibitory and clearance-accelerating mechanisms from Japanese practice. Semin Thromb Hemost 2025; 51 (06) 706-716
• 10 Kaya Z, Özdemir O, Kayhan G, Akdemir Ö. Unusual comorbid conditions in three children with congenital dysfibrinogenemia: Lymphedema, leukemia, and sternal defect. Semin Thromb Hemost 2025; 51 (06) 717-720

Publication History

Article published online:
08 August 2025