Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome

• Published in: International journal of molecular sciences 2022-08, Vol.23 (16), p.8973
• Main Authors: Bradáčová, Pavla, Slavík, Luděk, Skoumalová, Adéla, Úlehlová, Jana, Kriegová, Eva, Manukyan, Gayane, Friedecký, David, Piskláková, Barbora, Ullrychová, Jana, Procházková, Jana, Hluší, Antonín
• Format: Article
• Language: English
• Subjects: Activated protein C; Annexin V; anti-cardiolipin; anti-β2-glycoprotein-I; Antibodies; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid antibodies; Antiphospholipid syndrome; Antiphospholipid Syndrome - complications; Autoimmune diseases; beta 2-Glycoprotein I; Cardiolipin; Coagulation factors; Criteria; Factor V; Female; Glycoproteins; Hemostasis; Hemostatics; Humans; Laboratories; Lupus; Mutation; Patients; Phosphatidylserine; Phosphatidylserines; Pregnancy; Pregnancy complications; Protein C; Proteins; Prothrombin; seronegative APS; Subgroups; Thrombin; thrombogenicity; Thrombosis; Thrombosis - etiology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23168973

Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.