Abstract Number: PB1782
Meeting: ISTH 2020 Congress
Background: Antithrombin (AT) is a serine protease inhibitor (serpins) and plays a critical role in in the regulation of coagulation. Its major function is the inhibition of activated coagulation factors predominantly activated factor X (FXa) and thrombin (FIIa). Growing evidence demonstrates that antithrombin also exerts anti-inflammatory function via direct interactions with endothelium and indirectly by inhibiting coagulation factors that may be involved in complement activation. We hypothesized that patients with inherited antithrombin deficiency may have increased complement activation if the above was true.
Aims: To determine whether markers of complement activation are altered in patients with antithrombin deficiency compared to with healthy controls.
Methods: Twenty patients with AT deficiency and 20 healthy controls were bled using flawless venipuncture and plasma was prepared in the normal way and stored at -80C. Complement activation was determined by measuring C3a, iC3b and C5a with specific anti-human antibodies by ELISA (Hycult Biotech). The complement haemolytic activity (CH50) was also determined using Diamedix EZ Complement Cells. All samples tested in the same run to prevent inter-assay variability. Statistical analysis was conducted using IBM SPSS 25; the data were non-parametric and so the Mann Whitney test was used to compare results.
Results: Medians (minimum and maximum) and p values for all four complement activation makers are presented in table 1.
|PARAMETERS||CH50 [%]||C3a [ng/ml]||C5a [ng/ml]||iC3b [ng/ml]|
|AT deficient patients median (min and max)||134 (103-159)||201 (71-561)||3 (1-13)||2 (2-4)|
|Control group median (min and max)||130 (104-147)||113 (54-367)||2 (1-26)||2 (1-4)|
Conclusions: In this small study there was a trend for all markers of complement activation to be increased in those with antithrombin deficiency. This reached significance for C3a. This data suggests a novel observation that there is increased complement activation in patients with inherited AT deficiency compared to healthy individuals. Further studies are ongoing.
To cite this abstract in AMA style:Mayger K, Young J, Greenlaw R, Smith RA, Sacks S, Hunt BJ. The Role of Antithrombin in Complement Activation: Pilot Data from Patients with Inherited Antithrombin Deficiency [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-role-of-antithrombin-in-complement-activation-pilot-data-from-patients-with-inherited-antithrombin-deficiency/. Accessed January 27, 2022.
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