Abstract Number: PB0715
Meeting: ISTH 2020 Congress
Background: Clot contraction is a key event of hemostasis, inducing compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin leading to the formation of an impermeable barrier. Red blood cell (RBC) retention in the clot is modulated by factor XIIIa crosslinking of α-chains. Patients with fibrinogen disorders have an abnormal clot structure and a heterogeneous clinical phenotype.
Aims: To assess if factor XIIIa-mediated RBC retention during clot contraction is altered in patients with hereditary fibrinogen.
Methods: Plasma rich plasma and whole blood clot contraction in the absence or presence of FXIIIa inhibitor (T101) was studied in hypofibrinogenemic and dysfibrinogenemic patients with either a bleeding and/or thrombotic phenotype, or asymptomatic. Contracted clots were weighed at 120 minutes and prepared for scanning electron microscopy.
Results: Overall, 4 dysfibrinogenemic and 6 hypofibrinogenemic patients were included (Table 1). The kinetics of clot contraction were similar between controls and patients, but clots formed from hypofibrinogenemic patients were significantly smaller and lighter (0.012±0.06 vs 0.029±0.09 mg/µl; p=0.001). Clot contraction was almost complete within the first hour in all samples. The contraction slope significantly varied among patients and was correlated to rate of polymerisation as measured by turbidity. There was no correlation between the clot contraction parameters and the clinical phenotype nor with the causative mutation. Inhibition of FXIII resulted in lighter and smaller clots in controls (0.477±0.33) and hypofibrinogenemia (0.314±0.27) but not in dysfibrinogenemia samples with both FGA and FGG variants (0.933±0.62; p=0.01). Scanning electron microscopy confirmed the presence of polyhedrocytes inside the contracted clots.
Conclusions: Clot contraction was slower in hypofibrinogenemic patients compared to controls, highlighting the influence of fibrinogen concentration in this process. FXIII-induced RBC retention in the clot was altered in all tested dysfibrinogenemia samples. Further investigations will allow to determine whether these observations could be correlated to patients’ clinical phenotype.
|FGA Arg35His||Dysfibrinogenemia||Asymptomatic||Fg:Act 0.7 g/L||Fg:Ag 2.8 g/L|
|FGB Trp 470X||Hypofibrinogenemia||Bleeding||1.3||1.6|
[Patients’ biological and clinical data]
To cite this abstract in AMA style:Marchi R, Macrae F, Neerman-Arbez M, Fontana P, Ariëns R, Casini A. Factor XIIIa-Mediated Red Blood Cell Retention in the Contracting Clot Is Impaired in Hereditary Dysfibrinogenemia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/factor-xiiia-mediated-red-blood-cell-retention-in-the-contracting-clot-is-impaired-in-hereditary-dysfibrinogenemia/. Accessed December 2, 2022.
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