Antifosfolipidni sindrom i trudnoća

Željka Kardum

Antiphospholipid syndrome (APS) is a chronic autoimmune disease characterized by the presence of antiphospholipid autoantibodies, such as anticardiolipin antibodies (aCL), antiβ2 glycoprotein 1 antibodies (aβ2GP1), and circulating lupus anticoagulant (LA).
The clinical festures include recurrent thrombosis of the arteries, veins, and microvasculature, which are the main features of vascular APS (vAPS), and/or obstetric complications that are part of obstetric APS (oAPS). Obstetric complications have a direct effect on maternal and fetal morbidity, causing recurrent pregnancy miscarriages, fetal death, and signs of placental insufficiency that include preeclampsia, intrauterine growth restriction, and HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelets) syndrome.
In APS, thrombosis is the most prominent feature of the disease. In oAPS, the main pathological findings include impaired spiral artery remodeling, decidua inflammation with neutrophil infiltration, local tumor necrosis factor (TNF) -α production, deposition of complement split products, and placental infarction, which suggest a state of thrombo-inflammation. Antiphospholipid antibodies have both a direct embryotoxic and an effect on the placenta, causing a pro-inflammatory state, disrupting trophoblast development and implantation, and impaired spiral artery remodeling. Standard oAPS therapy includes low-molecular-weight heparin and low-dose aspirin. Approximately 20–30% of oAPS patients do not benefit from standard treatment, and additional therapeutic options are necessary in those refractory cases, which may include small doses of prednisolone, hydroxychloroquine, plasmapheresis, immunoglobulins, TNF-α inhibitors, statins, and eculizuma.

Antifosfolipidni sindrom (APS) je kronična autoimunosna bolest karakterizirana prisutnošću antifosfolipidnih protutijela kao što su lupus antikoagulans (LA), antikardiolipinska protutijela (aCl) i anti-β2 glikoprotein I protutijela (aβ2GPI ). Klinička slika može varirati od pojave tromboze vena, arterija i mikrožilja koja je klinička slika tzv. vaskularnog APS-a (vAPS) i/ili opstetričkih komplikacija koje su obilježje opstetričkog APS-a (oAPS). Najčešća su komplikacija oAPS-a višestruki pobačaji, fetalna smrt te prijevremeni porod zbog insuficijencije posteljice koja uzrokuje zastoj u fetalnom rastu, preeklampsiju ili HELLP-sindrom (hemoliza, povišeni jetreni enzimi i niski trombociti; engl. hemolysis, elevated liver transaminase enzymes, low platelet counts). U vAPS-u je tromboza vodeće kliničko obilježje bolesti, dok u oAPS-u vodeća patološka obilježja uključuju nepotpuno remodeliranje spiralnih arterija, upalu decidue uz infiltraciju neutrofila, lokalnu sintezu čimbenika tumorske nekroze alfa (engl. tumor necrosis factor [TNF] -α), odlaganje komponenti komplementa i infarkte posteljice koji upućuju na stanje tromboinflamacije. Antifosfolipidna protutijela imaju izravan embriotoksični učinak djelujući i na embrij i na posteljicu, aktivirajući proupalno stanje i uzrokujući prekid normalnog razvoja trofoblasta te posljedično dovode do nemogućnosti implantacije i nepotpunog remodeliranja spiralnih arterija. Standardna terapija u oAPS-u uključuje niskomolekularni heparin i niske doze acetilsalicilne kiseline. U 20 – 30% slučajeva bolesnice s oAPS-om imat će opstetričke komplikacije unatoč standardnoj terapiji. U tim refraktornim slučajevima dodatna terapija je potrebna, a može uključivati male doze prednizolona, hidroksiklorokin, plazmaferezu, imunoglobuline, TNF-α inhibitore, statine i ekulizumab.