Abstract Number: PB0477
Meeting: ISTH 2021 Congress
Background: It is surmised that differences in coagulation phenotype contribute to the variable bleeding phenotype in severe haemophilia A (SHA).
Aims: We measured thrombin generation (TGA) in a cohort of SHA in the absence of FVIII:C utilizing three concentrations of tissue factor (TF).
Methods: Venous blood (20mL) was collected from 25 SHA patients and 6 normal donors (NDs) (3.2% citrated Sarstedt Monovette™ tube Numbrecht, CTI 18 μg/mL, Cambridge Biosciences) and triple spun platelet poor plasma (PPP) prepared. Addition of 20 BU/mL FVIII:C antibody (Cambridge Biosciences) reduced FVIII:C activity to < 1IU/dL. TGA was triggered with 0.5, 1 and 2 pM TF (Innovin®, Siemens UK) and 4uM phospholipid (Rossix, Quadratech Diagnostics Ltd). 20 μL of trigger and 80 μL of PPP were pre-incubated for 5 min at 37°C and 20 μL FluCa (0.1 M CaCl2/Fluorogenic substrate, Thrombinoscope BV) initiated TGA (Hemker method with calibrator). (Ethical approval, Katharine Dormandy coagulation research plasma bank, REC No:14/YH/1272).
Results: Patients demonstrated decreased TF concentration dependent thrombin generating capacity compared to NDs. 0.5, 1 and 2pM TF, SHA and NDs, Median (5-95% quantiles) respectively. Lagtime (mins) 9.5(5.2-23.1), 5.7(3.7-11.3), 3.3(2.7-7.1); 6.1(4.4-9.2), 3.7(3.4-4.8), 3.3(2.5-3.6). ttPeak (mins) 50.2(19.6-62.7), 28.5(18.3-53.2), 15.8(8.4-28.8); 43.6(26.2-55.0), 17.7(11.0-24.7), 12.1(8.4-16.9). Peak (nM FIIa) 6.9(1.6-15.2), 12.0(4.6-22.5), 27.7(10.2-53.0); 9.1(6.2-13.0), 20.7(10.3-30.0), 66.6(55.1-97.1). SHA results showed a highly significant correlation between Lagtime and ttPeak, R=0.83 (0.5TF) p= .01,0.85 (1TF) p=0, 0.61 (2TF) p=0. Peak and ETP (endogenous thrombin potential) showed weak correlation with these parameters (data not shown).
Conclusions: TG in SHA demonstrates less TF dependent thrombin generating capacity than normal donors in the absence of FVIII:C activity with greater variation in response. Lack of correlation between ETP and Peak with Lagtime and ttPeak suggest that the latter are independent variables that may contribute to phenotypic differences.
To cite this abstract in AMA style:Hamid C, Dunster J, Aradom E, McVey J, Chowdary P. Differences in Thrombin Generating Capacity in Severe Haemophilia A [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/differences-in-thrombin-generating-capacity-in-severe-haemophilia-a/. Accessed August 15, 2022.
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