Young women are a high-risk group.
Given the high number of patients with morbid pregnancies in our country and the fact that some of them have an unknown etiology, it is necessary to be alert to the presence of antiphospholipid syndrome. Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease clinically manifested by symptoms such as arterial and venous thrombosis, habitual miscarriage and thrombocytopenia, with the presence of antiphospholipid antibodies (aPL) in the serum, and the above-mentioned symptoms can be present individually or in combination.
The term was first identified and introduced by Hughes et al. in 1986. The disease can occur either secondary to systemic lupus erythematosus (SLE) or other autoimmune diseases, called secondary antiphospholipid syndrome (SAPS), or alone, known as primary antiphospholipid syndrome (PAPS). There is also a rare clinical form of malignant APS (CAPS), which presents as APS involving at least 3 different organs or systems occurring simultaneously within a short period of time (no more than 1 week) and with histopathologically confirmed small vessel occlusive-like changes in one or more organs or systems, which can result in multi-organ failure or even death.
APS is a common acquired thrombophilia with the following characteristics of thromboembolism: thrombus can occur in all vessels, thrombus can occur in a single site or multiple sites simultaneously, and intermittent episodes of recurrent thrombosis. The etiology of primary APS is still unclear and may be related to genetics, infection and other factors.
It is common in adults, mostly in young people, with a male to female incidence ratio of 1:9 and a median age of 30 years for women. Common triggers of catastrophic APS include infection, surgical operations (e.g., biopsy, tooth extraction, etc.), anticoagulant withdrawal or underdose, tumors, lupus activity, and oral contraceptives, as well as about 30% of patients without a definite precipitating event.
Placental thrombosis as a cause of miscarriage.
There is no significant difference in the clinical presentation of primary and secondary APS; any organ can be involved, and the manifestations of the disease vary between organs or tissues. Catastrophic APS presenting with large vessel thrombosis is relatively rare and more often manifests as small vessel acute thrombotic microangiopathy (TMA)-like changes involving multiple organs. The kidney is the most commonly involved organ in catastrophic APS, followed by the lung, central nervous system, heart, and skin, etc. Disseminated intravascular coagulation occurs in approximately 25% of catastrophic APS.
In addition to arteriovenous thrombosis, thrombocytopenia is another important manifestation of APS. The main manifestations of antiphospholipid syndrome nephropathy are renal artery thrombosis/stenosis, renal ischemic necrosis, renal victory hypertension, renal vein thrombosis, microvascular occlusive nephropathy, and associated end-stage renal disease.
Placental vascular thrombosis and infarction can lead to placental insufficiency, which in turn can cause habitual abortion, intrauterine distress, intrauterine growth retardation, or stillbirth. A typical APS miscarriage occurs after 10 weeks of gestation or earlier, and serious complications can occur in pregnant women with APS, including early pre-eclampsia, hemolysis, elevated liver enzymes, and thrombocytopenia.
There are six types of relevant diagnoses.
The diagnosis of primary APS relies mainly on clinical manifestations and laboratory tests, and other autoimmune diseases and thrombosis caused by infections and tumors must also be excluded. APS should be considered possible when patients present with moderate to high titers of anticardiolipin antibodies (aCL) or lupus-like anticoagulant (LA) antibodies and have
I. Unexplained arterial or venous thrombosis.
II. Thrombosis occurring in an uncommon site (e.g., kidney or adrenal gland).
III. Thrombosis occurring in young people.
IV. Recurrent thrombosis.
V. Recurrent episodes of thrombocytopenia.
VI. Miscarriage occurring in the middle and late stages of pregnancy. Venous thrombosis needs to be differentiated from protein C, protein S and antithrombin III deficiency, thrombotic thrombocytopenic purpura (TTP), fibrinolytic abnormalities, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria, leukoaraiosis and thrombosis associated with oral contraceptives. Arterial thrombosis needs to be differentiated from hyperlipidemia, diabetic vasculopathy, thrombo-occlusive vasculitis, vasculitis, and hypertension.
According to the 2006 Sydney criteria, the relevant diagnoses mainly include
I. Confirmation of APS: presence of thrombosis or recurrent miscarriage with positive aPL.
II. probable APS or pre-APS: refers to positive aPL with clinical manifestations suggestive of APS, such as reticulocytosis, chorea, thrombocytopenia, miscarriage and heart valve lesions, but not yet meeting the diagnostic criteria.
III. Seronegative APS: There are typical clinical manifestations of APS, such as arteriovenous thrombosis and morbid pregnancy, but aPL, anti-β2GPI antibodies and other laboratory tests for aPL are negative.
IV. Asymptomatic APS: positive for aPL, but no associated clinical manifestations.
V. Microvascular APS: refers to the absence of macrovascular thrombosis, but exhibits microvascular thrombosis and positive aPL, including TTP, hemolytic-uremic syndrome (HUS), catastrophic antiphospholipid antibody syndrome (CAPS), and HELLP syndrome (hemolysis, elevated liver enzymes, and thrombocytopenia syndrome).
Warfarin is contraindicated in the treatment of pregnant women.
Treatment of APS is primarily symptomatic to prevent recurrence of thrombosis and miscarriage. Treatment with hormones or immunosuppressive agents is generally not required, except in special cases such as secondary antiphospholipid syndrome. Anticoagulation therapy is mainly used in patients with aPL positive with thrombosis, or in antibody positive pregnant women with a history of recurrent miscarriage. Anticoagulation is not indicated for asymptomatic antibody-positive patients. It is important to note that the commonly used anticoagulant drug Warfarin has teratogenic effects and is contraindicated in pregnant women.
Pregnant women with APS should be treated as follows.
I. No previous history of miscarriage, or miscarriage occurring in the first 10 weeks of gestation, usually treated with low-dose aspirin.
II. Previous history of miscarriage after 10 weeks of gestation, after confirmation of pregnancy, heparin should be used until discontinued before delivery.
III. Prior history of thrombosis, anticoagulation with heparin or low molecular heparin should be started before pregnancy.
IV. For postpartum treatment, anticoagulation therapy should be continued for 6-12 weeks after delivery because of the great risk of thrombosis within 3 months after delivery, and if possible, heparin can be changed to warfarin 2-3 weeks after delivery. Both Warfarin and heparin do not affect breastfeeding.