Clinical and laboratory diagnosis of autoimmune factor V inhibitors: A single institutional experience.

BACKGROUND: Coagulation factor V inhibitors (FV-i) may occur in patients with congenital FV deficiency or previously hemostatically normal patients (autoimmune (AI)-FV-i). Most of the published literature is confined to case reports. OBJECTIVE: Describe clinical and laboratory features of AI-FV-i identified through the Special Coagulation Laboratory at Mayo Clinic, Rochester, Minnesota. METHODS: In this retrospective study individuals with FV-i screens performed from January 1999 to February 2017 were identified through the special coagulation laboratory database. Clinical presentation, management, and outcomes were collected for our institutional patients while detailed laboratory data was collected for all tested patients. RESULTS: Of patients with FV-i managed at our institution, 2/8 (25%) patients experienced no bleeding. There was no correlation between inhibitor titers and/or FV activity (FV:C) levels and clinical bleeding. Hemostatic management included fresh frozen plasma, platelet transfusion, activated prothrombin complex concentrates, and recombinant factor VIIa. Only 2 patients received immunomodulatory treatment. FV-i mixing studies with normal pooled plasma (n = 26) demonstrated inhibition on immediate mix but progressive inhibition after 1 h of incubation could not be demonstrated. 71% of platelet neutralization procedures were falsely positive while 59% of DRVVT assays were indeterminate. CONCLUSION: FV-i demonstrates immediate inhibition on mixing studies; however our limited data does not support a time dependent inhibition. Our clinical cohort confirms the variable clinical phenotype for individuals with FV-i and supports the notion that management of FV-i should be guided by clinical symptoms and not FV:C or FV-i titer.

Local verification and assignment of mean normal prothrombin time and International Sensitivity Index values across various instruments: recent experience and outcome from North America.

Warfarin dosing relies on accurate measurements of international normalized ratio (INR), which is calculated from the prothrombin time (PT), International Sensitivity Index international sensitivity index (ISI) of the thromboplastin, and the geometric mean of normal PT (MNPT). However, ISI assignments of certain reagent/instrument combinations are frequently unavailable, especially when the reagent and instrument are not from the same manufacturer. The effort to be in compliance with widely endorsed Clinical and Laboratory Standards Institute (CLSI) guidelines by locally verifying or assigning an ISI to an unsupported reagent/instrument combination is further hindered by the lack of US Food and Drug Administration (FDA)-approved certified plasmas designated for a particular reagent/instrument combination. The objectives of the study include development of a process to verify/assign ISI and MNPT of a single thromboplastin reagent from one manufacturer across multiple instruments including several from another manufacturer and across several campuses of a single institution, the Mayo Clinic. In this study, RecombiPlasTin 2G (R2G), was evaluated on the ACL TOP 700 (IL), STA-R Evolution, STA Compact, and STA Satellite. Random normal donor samples (n = 25) were used to verify/assign MNPT. A subset of the normal donors (n = 8) and 13 warfarin pools (INR range: 1.3-3.9), created from stable warfarin patient plasma, were used for ISI verification/assignment. The manufacturer's assigned ISI was first verified on the ACL TOP 700 (reference method), then assigned on three unsupported instruments using orthogonal regression analysis. The MNPT and manufacturer assigned ISI (11.0, 0.95) were verified on the ACL TOP 700 and subsequently assigned on the STA-R Evolution (11.6, 1.04); STA Compact (11.5, 1.02); and STA Satellite (10.9, 0.99). Linear correlations of the INR results from all the four instruments demonstrated an r2 > 0.99. This process provides a reproducible approach to assigning ISIs on unsupported reagent/instrument combinations. Our data also confirm that ISIs of the same PT reagent differ significantly on different instruments, thus confirming the requirement for evaluations and validation of ISIs for different reagent/instrument combinations.