Abstract Number: PB0717
Meeting: ISTH 2020 Congress
Background: The clinical course of hereditary hypo- or dysfibrinogenemia is often unpredictable. Asymptomatic individuals at the time of diagnosis may carry a lifetime risk of adverse outcomes. Standard coagulation assays fail to predict the patient´s clinical phenotype (CP).
Aims: To assess the clinical outcome by studying thrombin generation (TG) and ROTEM in relation to various phenotypes.
Methods: 24 patients, 15 from Finland (11 unrelated families) and 9 unrelated from Switzerland were studied. Six experienced bleeding, 5 thrombotic complications, and 13 were asymptomatic with a familiar history of bleeds in 3 and thrombosis in 6. Fibrinogen (Fg) activity and antigen, and TG by Genesia with both Bleed- (STG-BLS) and ThrombosSreen (STG-TS) in the presence or absence of intrinsic pathway influence (corn-trypsin inhibitor, CTI) were studied in all. ROTEM was available for 11 patients. Genotyping was performed for 15 patients.
Results: Overall, 12 patients had hypo-, 10 dys- and 2 hypodysfibrinogenemia. Of the 15 different genetic defects, 6 were in the Fg gamma-chain, 4 in Fg Bbeta-chain and 3 in Fg Aalpha-chain. High inter-individual variation (up to 7-fold) in all TG variables with both STG-BLS and STG-TS was observed among the different groups, irrespectively of CP or Fg levels, use of TM (Figures 1 and 2) or of CTI. No correlation between Genesia and CP could be detected. FIBTEM picked up hypofibrinogenemia (MCF < 5 mm) in all patients, while being normal in dysfibrinogenemia. MCF by FIBTEM correlated with Fg antigen, unlike activity.
Conclusions: CP failed to associate with Rotem or TG in Genesia. FIBTEM detected hypofibrinogenemia but was unable to depict dysfunctional fibrinogen. The accordance of CP, Fg levels, fibrin clot structure and Genesia with genotypes will be explored as the next step. The impact of fibrin polymerization at the level of TG potential and FXIIIa activities may offer an underlying mechanism for these differences.
To cite this abstract in AMA style:Szanto T, Lassila R, Lemponen M, Lehtinen E, Neerman-Arbez M, Casini A. High Individual Variation of Thrombin Generation by Genesia and Correlation of Fibrin-Associated ROTEM with Fibrinogen Activity in Patients with Congenital Fibrinogen Defects [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/high-individual-variation-of-thrombin-generation-by-genesia-and-correlation-of-fibrin-associated-rotem-with-fibrinogen-activity-in-patients-with-congenital-fibrinogen-defects/. Accessed May 6, 2021.
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