Anti-phospholipid syndrome (APS) is a general term for a group of clinical signs caused by antiphospholipid antibodies, mainly manifesting as thrombosis, habitual abortion, thrombocytopenia, and neuropsychiatric symptoms. Antiphospholipid antibodies are composed of various components, one of which is very important is anti-cardiolipin antibody, therefore, antiphospholipid syndrome is also called anti-cardiolipin syndrome. 30% to 40% of lupus erythematosus patients are positive for antiphospholipid antibodies, antiphospholipid antibodies can also appear in immune diseases such as rheumatoid arthritis and dry syndrome, even in cerebrovascular accidents, hematological diseases, tumors, etc. Certain drugs such as chlorpromazine can also cause antiphospholipid antibodies. Some drugs such as chlorpromazine can also cause positive antiphospholipid antibodies. Antiphospholipid syndromes that are not associated with other diseases are called primary antiphospholipid syndromes, while those that develop on the basis of a certain disease are called secondary antiphospholipid syndromes. Some antiphospholipid syndromes manifest as small blood vessel thrombosis in multiple organs within a short period of time, causing infarction of brain, heart, liver, kidney and intestine, and the condition is so dangerous that it is called catastrophic antiphospholipid syndrome.
I. Key points of medical history taking
1. Present medical history.
(1) The course of the disease: the urgency of the onset of the disease, the date of onset.
(2) Main symptoms.
a thrombosis-related symptoms: venous thrombosis: mainly deep vein thrombosis, including kidney, retina, inferior vena cava; arterial thrombosis: stroke, myocardial infarction, pulmonary and renal infarction-related symptoms;
b spontaneous abortion, habitual abortion and intrauterine fetal death;
c thrombocytopenia: epistaxis, purpura and gum bleeding symptoms;
d reticular cyanosis of the skin.
e neuropsychiatric symptoms: cerebral thrombosis, cerebral hemorrhage, abnormal mental behavior, epilepsy, chorea and spinal cord lesions.
2. Past history: any history of systemic lupus erythematosus, rheumatoid arthritis, dry syndrome, etc., and any history of special medication.
3. Personal history: Any history of recurrent spontaneous miscarriage and stillbirth in female patients.
4. Family history: Is there any history of similar diseases in the family?
II. Key points of physical examination
Skin: skin cyanosis, reticular cyanosis, subcutaneous nodules, finger (toe) gangrene, chronic lower limb ulcers, vasculitis-like spots, unilateral lower limb swelling.
Heart: heart murmur, arrhythmia, etc.
Lungs: decreased breath sounds, signs of pulmonary hypertension, hyper P2.
Abdomen: liver size, pressure pain, tenderness.
Ophthalmologic examination: presence of retinal vascular thrombosis.
Neurological: presence of impaired consciousness, aphasia, sensory and motor abnormalities, presence of pathological signs.
Third, auxiliary examinations.
1. Laboratory tests.
(1) Anti-cardiolipin antibody;
(2) Lupus anticoagulant;
(3) Anti-nuclear antibody, anti-double-stranded DNA antibody and anti-ENA antibody;
(4) Routine examination: blood and urine routine, liver and kidney function and electrolytes; plasma immunoglobulin, protein electrophoresis, complement and blood sedimentation, etc;
2.Imaging and other special examinations.
(1) Vascular ultrasound: the preferred non-invasive method for diagnosing large arterial or venous thrombosis;
(2) Angiography: the gold standard for the diagnosis of intravascular thrombosis;
(3) Computed tomography (CT): meaningful for the diagnosis of cerebral infarction and pulmonary embolism;
(4) Magnetic resonance imaging (MRI): diagnosis of cerebrovascular diseases and beneficial for the diagnosis of large vessel lesions such as aorta and vena cava.
3. Histopathological biopsy: used to identify inflammatory vascular occlusion.
IV. Diagnosis and differential diagnosis
1.Diagnostic points
Antiphospholipid syndrome is clinically classified into: 1) primary antiphospholipid syndrome; 2) secondary to systemic lupus erythematosus; 3) secondary to lupus-like disease; 4) secondary to other autoimmune diseases.
Common diagnostic criteria 1988 Asherson diagnostic criteria
Clinical manifestations: ① venous thrombosis; ② arterial thrombosis; ③ habitual abortion; ④ thrombocytopenia
Laboratory history indicators: ①IgG antiphospholipid antibody (APL); ②IgM APL; ③LA positive
Diagnostic criteria: ① 1 clinical manifestation index plus 1 laboratory index; ② 2 positive APL with an interval of more than 3 months; ③ 5-year follow-up to exclude SLE or other autoimmune diseases.
Diagnostic criteria of Alarcon-Segovia 1989 classification
A definitive diagnosis is required to satisfy.
(i) two or more of the following clinical manifestations
(i) recurrent spontaneous abortion; (ii) venous thrombosis; (iii) arterial obstruction; (iv) lower extremity ulcers; (v) reticulocytosis; (vi) hemolytic anemia; (vii) thrombocytopenia
(ii) With high titer APL (IgG or IgM>5SD)
Suspicious: 1 clinical manifestation plus high titer APL or two or more clinical manifestations plus positive APL (IgG or IgM: 2-5SD)
2.Differential diagnosis
(1) Other diseases causing recurrent transvenous thromboembolism: including certain diseases with deficiency of anticoagulant factors; abnormal fibrinolysis; nephrotic syndrome; true erythrocytosis; leukoaraiosis; paroxysmal sleep hemoglobinuria and oral contraceptives, etc.
(2) Other diseases causing arterial occlusive disease: including hyperlipidemia, diabetes mellitus, hypertension, vasculitis, hyperhomocysteinemia, thrombo-occlusive vasculitis and sickle cell disease.
(3) Other diseases that cause thrombocytopenia: aplastic anemia, thrombocytopenic purpura, etc.
V. Treatment plan
The main goal of treatment is to inhibit thrombosis
1.Anti-platelet aggregation: Aspirin 150mg-350mg qd, small dose aspirin 80mg qd is also recommended.
2, anticoagulation: Warfarin has teratogenic effects and is not used in women of childbearing age. Low molecular heparin rarely causes bleeding and does not pass through the placenta.
3.For patients who have thrombosis, antithrombotic therapy is given in the acute stage, and surgical thrombus retrieval therapy is available in the acute stage of lower limb deep vein thrombosis.
4.For severe thrombocytopenia, glucocorticoids and immunosuppressants should be added.
5.Treatment during pregnancy
(1) Prevention of miscarriage: prednisone (40mg/d) combined with low-dose aspirin (about 80mg/d). The success rate of pregnancy with this regimen has been reported to be 60% to 70%. However, long-term treatment with prednisone is prone to side effects such as Cushing’s syndrome, adrenal insufficiency, secondary infection, diabetes mellitus, IUGR, preeclampsia and premature rupture of membranes. Trials have proven that heparin + low-dose aspirin is a better treatment. If heparin is effective, try not to use large amounts of prednisone to prevent osteoporotic fractures and other side effects.
(2) Prevention of thrombosis:The risk of thrombosis increases during pregnancy in pregnant women with APS. Heparin prophylaxis should also be given during pregnancy in those without a history of thrombosis. Heparin should be applied in high doses (20,000 U/d) in the middle and late stages of pregnancy, because small doses are not sufficient to prevent thrombosis. Low molecular weight heparin is safe for use during pregnancy. If low molecular weight heparin is used during pregnancy, there is an increased risk of bleeding during local anesthesia, and pubic plexus or epidural anesthesia must be instituted 24h after discontinuation.
(3) Improve placental function:Patients with APS should be closely monitored in the outpatient clinic for a long time, with weekly antenatal checkups and NST every 2 weeks for early detection of preeclampsia, fetal growth retardation and placental dysfunction. Starting from 18-20 weeks, ultrasound examination should be done every 4-6 weeks; after 32 weeks, NST should be done twice a week and amniotic fluid examination should be done. Patients should be taught to make fetal movement count. Dexamethasone is recommended for prenatal use, but should not be used repeatedly.
(4) Postpartum treatment:Patients should be informed of the possibility of other complications of APS after delivery. Anticoagulation should be continued until 6 weeks postpartum to reduce the risk of maternal thrombosis. Warfarin is available for postpartum anticoagulation. Patients with previous thrombosis should receive lifelong anticoagulation. oral estrogen-based contraceptives are contraindicated in patients with APL.
6. Observation during the course of the disease
Pay attention to monitoring blood coagulation analysis and blood picture during the course of the disease, and check liver function and kidney function when applying hormones and immunosuppressants. Pay attention to long-term close monitoring during pregnancy for early detection of pre-eclampsia, fetal growth retardation and placental dysfunction.
VI. Prognosis estimation
The prognosis mainly depends on the site of thrombosis and the degree of involvement of internal organs. Multiple sites of embolism, rapid progression and significantly higher titers of antiphospholipid antibodies are indicative of prognosis.