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.

External quality assessment (EQA) is used to evaluate laboratory performance in tests of hemostasis; however, some esoteric tests are performed by too few centers in any one EQA program to allow valid statistical assessment. To explore the feasibility of pooling data from several EQA providers, an exercise was carried out by the External Quality Assurance in Thrombosis and Haemostasis group, using the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (SSC) plasma standard for thrombophilia screening assays. Six EQA providers took part in this exercise, distributing the SSC plasma standard as a "blinded" sample to participants for thrombophilia tests between November 2020 and December 2021.

Automation of a Factor XIII Activity Assay Utilizing a Plasma Blank Measurement.

Factor XIII (FXIII) is an essential coagulation factor that stabilizes fibrin clots and allows the clot to resist fibrinolysis. Inherited or acquired FXIII deficiency is a severe bleeding disorder with manifestations that can include fatal intracranial hemorrhage. Accurate FXIII laboratory testing is necessary for diagnosis, subtyping, and treatment monitoring.

Von Willebrand factor testing ratios in the diagnosis and subtyping of von Willebrand disease.

Von Willebrand disease (VWD) is a common bleeding disorder of platelet adhesion with six currently recognized subtypes. Laboratory diagnosis consists of an initial test panel including antigen, activity and factor VIII measurements, sometimes followed by further specialized testing. VWF activity/antigen testing ratios help to differentiate type 1 and type 2 disease, which is important for selection of proper therapy.

Analysis of College of American Pathologists von Willebrand Factor Proficiency Testing Program.

Von Willebrand factor (VWF) level and/or function is altered in von Willebrand disease (VWD), the most common heritable bleeding disorder worldwide. Laboratory assessment of VWF is continually evolving. Historically, the primary method for the assessment of VWF platelet-binding activity was the ristocetin cofactor assay (VWF:RCo).

Analysis of College of American Pathologists von Willebrand Factor Proficiency Testing Program.

Von Willebrand factor (VWF) level and/or function is altered in von Willebrand disease (VWD), the most common heritable bleeding disorder worldwide. Laboratory assessment of VWF is continually evolving. Historically, the primary method for the assessment of VWF platelet-binding activity was the ristocetin cofactor assay (VWF:RCo).

Monoclonal and oligoclonal anti-platelet factor 4 antibodies mediate VITT.

Kanack and colleagues analyze anti-platelet factor 4 antibodies from 5 patients with vaccine-induced thrombotic thrombocytopenia (VITT) secondary to COVID-19 adenoviral vaccination and antibodies from patients with spontaneous heparin-induced thrombocytopenia (HIT) and classical HIT. VITT antibodies are monoclonal or oligoclonal, similar to spontaneous HIT, whereas classical HIT antibodies are polyclonal. Heparin inhibits antibody-induced platelet activation in VITT, suggesting that heparin should be considered for the treatment of VITT.

Establishing reference intervals for von Willebrand factor multimers.

Background: von Willebrand factor (VWF) multimers (VWF:MM) methodologies are technically difficult, laborious, time consuming, non-standardized and results vary between laboratories. A new semi automated VWF:MM assay is available for routine use (Sebia). Due to lack of reference values for VWF:MM fractions, results interpretation can be challenging in some cases.

Persistence of Ad26.COV2.S-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies.

Rare cases of COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.

Direct oral anticoagulant (DOAC) interference in hemostasis assays.

Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results.

Cryptogenic oozers and bruisers.

Bleeding disorders with normal, borderline, or nondiagnostic coagulation tests represent a diagnostic challenge. Disorders of primary hemostasis can be further evaluated by additional platelet function testing modalities, platelet electron microscopy, repeat von Willebrand disease testing, and specialized von Willebrand factor testing beyond the usual initial panel. Secondary hemostasis is further evaluated by coagulation factor assays, and factor XIII assays are used to diagnose disorders of fibrin clot stabilization.

ADAMTS13 testing update: Focus on laboratory aspects of difficult thrombotic thrombocytopenic purpura diagnoses and effects of new therapies.

TTP is a life-threatening disorder diagnosed using a combination of clinical information and laboratory results. ADAMTS13 activity and antibody testing represent a major advance in the field, but results can sometimes be difficult to interpret due to technical aspects of the tests and characteristics of the causative antibodies in acquired TTP. Genetic testing for ADAMTS13 mutations is also now available to assist with the diagnosis of inherited TTP.

Interlaboratory Performance in Measurement of Dabigatran and Rivaroxaban.

Context.—: Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios.

Objective.

Genotype and Phenotype Concordance for Pharmacogenetic Tests Through Proficiency Survey Testing.

Context.—: As pharmacogenetic testing is incorporated into routine care, it is essential for laboratories to provide accurate and consistent results. Certified laboratories must successfully complete proficiency testing.

Heparin-induced thrombocytopenia: An international assessment of the quality of laboratory testing.

Background: Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential to ensure timely treatment and prevent complications. Current diagnostic assays include enzyme-linked immunosorbent assays (ELISAs) and rapid immunoassays (RIs). RIs offer fast turnaround times but were not significantly represented in previous external proficiency testing challenges.

External Quality Assurance of Platelet Function Assays: Results of the College of American Pathologists Proficiency Testing Program.

Context.—: The College of American Pathologists (CAP) developed proficiency testing for platelet function assays by using blood collected by the participant added to challenge tubes containing either saline (normal) or tirofiban (abnormal).

Objective.

Venous Thrombotic Risk in Transgender Women Undergoing Estrogen Therapy: A Systematic Review and Metaanalysis.

Background: Transgender women are female individuals who were recorded men at birth based on natal sex. Supporting a person's gender identity improves their psychological health, and gender-affirming hormones reduce gender dysphoria and benefit mental health. For transgender women, estrogen administration has clinically significant benefits.