I. Clinical manifestations
Recurrent arteriovenous thrombosis, recurrent miscarriage, medium to high titers of antiphospholipid antibodies and thrombocytopenia, reticulocytosis, cardiac valvulopathy, anemia of lysis and chorea.
II. Treatment
1. Objective: To prevent thrombosis and avoid pregnancy failure.
2. Methods: mainly anticoagulation, hormonal and immunosuppressive therapy, other treatments such as IVIG, anti-CD20 monoclonal antibody and potential targeted therapy. Anticoagulation therapy is divided into two main areas, namely the treatment of APS combined with thrombosis and the treatment of APS pregnancy.
Third, the risk factors of APS thrombosis stratification
1. Type and titer of antiphospholipid antibodies. The correlation between antiphospholipid antibodies and thrombosis includes.
(2) Antibody type: LA>aβ2GP1>Acl,LA is the highest.
(3) Antibody titers: high titers > low titers.
(4) Number of antibodies: multiple > single, “triple positive” is the strongest predictor of thrombosis and adverse pregnancy risk.
(5) Target antigen site: high specificity of antibodies against Gly40-Arg43 peptide sequence in the D1 region of β2GP1.
2, autoimmune status, increased risk for those with combined autoimmune disease.
3, cardiovascular risk factors: hypertension as an independent risk factor, age, diabetes, lipids, obesity, smoking, high HCY, PC/PS/ATIII deficiency.
4.Site of thrombosis: arteriovenous, anatomical site, and history of arterial thrombosis are predictors of new arterial thrombosis.
4. Is primary prevention of thrombosis aPL-positive, asymptomatic patients in need of prevention?
Several studies have shown that the incidence of thrombosis in patients with triple-positive antibodies increases year by year with a longer medical history, and the incidence of thrombosis is significantly higher in those with combined autoimmune diseases.
1. Patients with primary prevention include.
(1) High-risk conditions: Low-molecular heparin is highly recommended – trauma, infection, surgery, prolonged braking.
(2) “Triple-positive” patients: low-dose aspirin.
(3) Patients with combined autoimmune disease: low-dose aspirin, hydroxychloroquine.
V. Secondary prevention of thrombosis 1.
1, about 4-6% patients, the risk of recurrence is higher in patients without anticoagulants, the risk of recurrence of thrombosis is 29% in triple-positive patients with anticoagulation, and 51% in patients without anticoagulation.
2. Venous thrombosis.
(1) Heparin/LMWH for at least 5 days, overlap with warfarin, switch to warfarin long-term use.
(2) Anticoagulation intensity: standard intensity INR2-3, high recurrence rate of standard intensity in triple-positive patients (45%/6 years).
(3) Anticoagulation duration: indefinite anticoagulation, high recurrence rate, ESP aPL lasts >6 months, patients with low titers and temporary triggers can continue anticoagulation for 3-6 months, review angiographic ultrasound and D-dimer before discontinuation.
3. Arterial thrombosis.
Indefinite anticoagulation, may be combined with low-dose aspirin, intensity of.
(1) standard intensity INR2-3 + low-dose aspirin.
(2) High intensity INR3-4.
(3) low-dose aspirin only.
VI. Treatment of other clinical manifestations of APS
1. Hematologic system: moderate to severe thrombocytopenia and AIHA, application of hormones, IVIG, immunosuppressants, rituximab, splenectomy. Primary prevention: aPL-positive with thrombocytopenia, especially in the presence of vascular risk factors or LAC-positive, should consider the application of aspirin or hydroxychloroquine for thromboprophylaxis.
2, neurological: chorea, myelitis, multiple sclerosis-like lesions: application of hormones, immunosuppressants; anticoagulation; symptomatic.
3, valve disease: oral aspirin for those without previous thrombosis and asymptomatic; oral anticoagulation for those with symptoms, secondary to heart valve disease at high risk of thromboembolic events; heart valve surgery, high risk of bleeding and thrombosis, strict testing of anticoagulation.
Seven, the new direction of APS treatment
1, elevated oxidative stress state: N-acetylcysteine inhibits ROS-mediated thrombosis; coenzyme Q10 inhibits aPL-mediated ROS formation.
2, Defective endothelial-type nitric oxide synthase function: Statin drugs upregulate eNOS activity. 3, Anti-β2GP1 antibody receptor activation: ApoE receptor 2 analogs and synthetic functional region I inhibit β2GP1-mediated thrombosis.
4, elevated tissue factor expression: protein disulfide isomerase inhibitors attenuate thrombotic events in mice; tatin drugs inhibit TF-dependent thrombosis in APS mice.
5, increased free thiol form of factor XI: disulfide isomerase and factor XI inhibitors attenuated thrombus formation in animal models.
6, Membrane association protein A5 shielding was disrupted: hydroxychloroquine inhibited the disruption of membrane association protein protective membrane by anti-β2GP1 antibody and reduced thrombus formation in mice.
7, antibody-mediated activation of complement C3 and C5: c5 inhibitor eculizumab improves CAPS.
8, Elevated TLR7, TLR8 expression: Hydroxychloroquine inhibits TLR7 activation and reduces thrombotic events in SLE.
9, Increased BAFF: BAFF inhibitors reduce thrombotic effects in a mouse model.