Antiphospholipid syndrome (APS) is a disorder characterized by recurrent arterial or venous thrombosis, morbid pregnancy and persistent positive antiphospholipid antibodies (APL), which can occur secondary to SLE or other autoimmune diseases, but can also occur alone (primary APS). There is no difference in the clinical presentation and laboratory tests between primary and secondary APS. The incidence of APS is significantly higher in women than in men, and the familial tendency of APS is not obvious, but antiphospholipid antibodies are often positive in relatives of patients.
I. Etiology
The occurrence of APS is also associated with other factors, as only some patients in the APL-positive population present with clinical manifestations. It has been suggested that these antibodies inhibit the coagulation waterfall reactions catalyzed by negatively charged phospholipids. Inhibition of protein C activation or neutralization of factor Va inactivation by APL may place the patient in a “pre-thrombotic state”. Cross-reactivity of anticardiolipin antibodies (ACL) with phosphatidylserine has been shown to bind to platelets and activate them, which can also cause thrombosis. Other possible mechanisms include increased platelet synthesis of thromboxane, inhibition of prostacyclin synthesis, and stimulation of tissue factor production by endothelial cells.
A plasma protein called β2 glycoprotein 1 (β2GP1) is of interest in the APL-mediated thrombosis process. It is now believed that APL can cause thrombosis by neutralizing the anticoagulant effect of β2GP1.
Autoimmune APL binds negatively charged phospholipids by binding to β2GP1 or other phospholipid-binding proteins and is β2GP1-dependent APL. However, infections such as syphilis, non-syphilis spirochetes, Burkholderia spirochetes, human immunodeficiency virus (HIV), leptospira and parasites, as well as drugs and malignancies induce the formation of antiphospholipid antibodies that usually bind directly to phospholipids and are β 2GP1 non-dependent antibodies.
II. Clinical manifestations
The clinical manifestations of APS vary in degree from asymptomatic APL positivity (no history of thrombosis or morbid pregnancy) to malignant APS (extensive thrombosis within a few days).
1. Vascular embolism
Arterial, venous and small vessel thrombosis of any tissue or organ can occur. It often occurs in rare sites, at a young age of onset, and repeatedly.
2.Miscarriage
A typical miscarriage in patients with APS occurs after 10 weeks of gestation, but also earlier than 10 weeks, the latter more often due to chromosomal or other genetic defects. early 3 months of pregnancy in patients with APS are mostly normal, later on, fetal growth is slow and amniotic fluid is reduced, and eclampsia and pre-eclampsia may also occur.
3. Non-specific manifestations
Reticulocytosis, thrombocytopenia, autoimmune hemolytic anemia, heart valve disease (valve redundancy or thickening), diffuse alveolar hemorrhage, pulmonary hypertension, multiple sclerosis-like syndrome, chorea or other myelopathies, etc.
4. Malignant antiphospholipid syndrome (CAPS)
This is a rare and sudden life-threatening complication that presents within days with extensive thrombosis of the middle and small arteries (despite the use of adequate anticoagulation therapy), causing stroke, cardiac, hepatic, adrenal, renal, and intestinal infarction, and peripheral tissue gangrene.
iii. tests
Positive lupus anticoagulant, ACL, or anti-β2GP1 antibodies help confirm the diagnosis.
IV. Diagnosis
1. Clinical criteria
(1) Vascular embolism ≥ 1 thrombosis of arteries, veins and small vessels of any tissue or organ.
(2) abnormal pregnancy
1) ≥1 unexplained morphologically normal fetal death occurring at 10 or more weeks of gestation, or 2) ≥1 morphologically normal preterm neonatal birth due to severe pre-eclampsia, eclampsia, or definite placental insufficiency occurring before 34 weeks of gestation, or 3) ≥3 unexplained spontaneous abortions occurring before 10 weeks of gestation, maternal anatomic or hormonal abnormalities must be excluded and chromosomal abnormalities in both parents.
2. Laboratory criteria
(1) At least 2 positive lupus anticoagulants at least 12 weeks apart.
(2) Intermediate/high titer IgG/IgM type ACL tested at least 2 times with an interval of at least 12 weeks.
(3) IgG/IgM anti-β2GP1 antibodies tested at least 2 times at an interval of at least 12 weeks.
At least 1 clinical criterion and 1 laboratory criterion must be met for the diagnosis of APS.
V. Prognosis
The long-term prognosis of patients with primary APS is poor. Patients with pulmonary hypertension, neuropathy, myocardial ischemia, nephropathy, limb gangrene, and malignant antiphospholipid syndrome have a poorer prognosis.
Despite prophylaxis, serious perioperative complications may occur in patients with APS because of the increased risk of thrombosis at the time of surgery. Therefore, a clear coping strategy should be developed before any procedure, with pharmacological and physical anticoagulation measures to minimize the time without anticoagulation and minimize intravascular manipulation and testing.