Diagnosis of factor VIII deficiency

Abstract

Summary. The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, onestage and two-stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one-stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one-stage and two-stage assays are reviewed and discussed.

Analytical variation in factor VIII one‐stage and chromogenic assays: Experiences from the ECAT external quality assessment programme

“…The results of this study showed that the variation between laboratories is higher when FVIII activity levels are lower, both in the OSA and CSA. These results are consistent with the results by Verbruggen et al in 2008, who also showed a J‐shaped relationship between FVIII activity levels and CV, for FVIII results predominantly from the OSA. In their study, the CV increased strongly below 0.20 IU/mL with a maximal CV between 30% and 40%.…”

“…In the ECAT surveys, many different lot numbers were used by the different laboratories, and therefore, we do not expect that typical properties of a single lot will be able to influence the results from the ECAT surveys. Finally, previous studies have shown that some activators (STA Cephascreen [Stago] and Actin FS [Siemens]) are not optimal in diagnosing severe haemophilia A patients which may also have influenced the FVIII activity levels found in this study …”

“…The use of varying products may partially explain the between‐laboratory variation in FVIII results. However, it is still unclear what the precise impact is of varying in reagents and equipment on the variability of FVIII activity measurements . A possible explanation may be that particular companies provide the majority of products applied for the haemostatic testing which is standard in haemophilia.…”

Evaluation of an automated chromogenic assay for Factor VIII clotting activity measurement in patients affected by haemophilia A

“…Haemophilia A diagnosis is usually done considering family and/or personal history of bleeding and the presence of an isolated prolonged activated partial thromboplastin time (aPTT) justified by reduced or absent FVIII:C in patient's plasma. Based on the residual FVIII:C, haemophilia A is defined as severe (FVIII:C < 1 IU/dL), moderate (FVIII:C 1‐5 IU/dL) or mild (FVIII:C 6‐40 IU/dL) . Usually age at diagnosis and bleeding frequency are inversely related to the residual FVIII:C levels.…”

Considerations in the laboratory assessment of haemostasis

“…The APTT reagent is also the test base for one-stage factor assays and the variable responsiveness is also propagated to these assays. The importance of choosing the correct APTT reagents for FVIII:C and FIX:C activity assays was recently shown by two investigations that illustrate how the diagnostic value can differ between reagents [14,15]. The laboratory phenotype known as discrepant mild haemophilia A is another example where the APTT-based onestage FVIII:C assay may be poorly correlated to the bleeding phenotype.…”