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.

Department of Hemato Oncology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Department of Immunology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Department of Internal Medicine 3 Nephrology Rheumatology and Endocrinology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Laboratory for Inherited Metabolic Disorders Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Laboratory of Molecular and Cellular Immunology Institute of Molecular Biology NAS RA Yerevan 0014 Armenia

Masaryk Hospital Usti nad Labem Department Clinical Hematology 40113 Usti nad Labem Czech Republic

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