antiphospholipid antibody syndrome
Introduction
Introduction to antiphospholipid antibody syndrome Antiphospholipid syndrome (APS) is a generic term for a group of clinical signs caused by antiphospholipid antibodies (APL antibodies). APL antibody is a group of antibodies that can immunoreact with a variety of antigenic substances containing phospholipid structures, mainly lupusanti-coagulant (LA), anti-cardiolipid antibody (ACL antibody), antiphospholipid Acid antibodies and anti-phosphatidylserine antibodies, and the like. The clinical manifestations associated with APL antibodies are thrombosis, habitual abortion, thrombocytopenia, and neuropsychiatric symptoms. APS is a common clinical manifestation in SLE patients. basic knowledge The proportion of illness: 0.002% Susceptible people: no specific population Mode of infection: non-infectious Complications: intracranial venous sinus thrombosis epilepsy dementia
Cause
Antiphospholipid antibody syndrome etiology
(1) Causes of the disease
Antiphospholipid antibodies refer to lupus anti-coagulant (LA), anti-cardiolipid antibody (ACL) or a group of autoantibodies against other phospholipids or phospholipid complexes. It is not clear that immunization of animals with bacteria can induce the production of antiphospholipid antibodies, indicating that infectious factors may play a role, in addition, may also be related to genetic factors, studies have reported that HLA-DR7 and DR4 appear in patients with antiphospholipid antibody syndrome The frequency of HLA-DR53 is higher in the anti-cardiolipin antibody-positive patients.
The most basic pathological feature of antiphospholipid antibody syndrome is thrombosis, and all clinical manifestations are related to it. In the past, antiphospholipid antibodies were only considered to be negatively charged phospholipids. It is now found that antiphospholipid antibodies may act more directly on one or more a plasma protein bound to phospholipids or a complex of these proteins and phospholipids, the most important of which is 2-glycoprotein I (2-GPI) and prothrombin, and the other phospholipid-binding protein has protein C, protein S and the surface molecules of vascular endothelial cells such as thrombomodulin, the role of antiphospholipid antibodies in thrombosis is mainly manifested in two aspects:
1 acts on vascular endothelial cells, mainly inhibiting the anticoagulant pathway of protein C. Under normal circumstances, thrombin induces the activation of protein C, and activated protein C can activate the factor under the synergistic action of protein S and factor V. V(Va) and VIII(VIIIa) are inactivated, thereby inhibiting the activation of thrombin, blocking the further development of blood coagulation to achieve a physiological balance between coagulation and anticoagulation, and antiphospholipid antibodies can inhibit the activation of protein C, thereby blocking the above reaction. The pathway inhibits the anticoagulant pathway of protein C and promotes coagulation and thrombosis. In addition, antiphospholipid antibodies can increase the expression of tissue factor (factor III) in vascular endothelial cells, thereby activating the exogenous coagulation pathway. The antiphospholipid antibody can inhibit the release of arachidonic acid from vascular endothelial cells, and reduce the production of prostacyclin and prostaglandin E2, thereby facilitating the adhesion of platelets to the vascular endothelium and thrombus formation.
2 acts on platelets, anti-phospholipid antibodies can increase the release of thromboxane A2 (Thromboxanes A2, TXA2), and thromboxane A2 can further activate other platelets and stimulate platelets to release various chemical factors, thereby causing the activation of platelet chain Activated platelets bind to fibrinogen through the surface receptors they express, and fibrinogen acts as a bridge to connect different platelets, leading to platelet aggregation and thrombosis.
(two) pathogenesis
The exact mechanism of APS antibody-induced APS is unclear. The mechanism of thrombosis in APS is related to APL antibody. Phospholipid itself is one of the components in normal anticoagulant system. Because APL antibody cross-reacts with certain proteins in anticoagulation system. Caused by abnormal hemagglutination, 2-glycoprotein I (2GPI, an apolipoprotein) itself has anticoagulant effect by inhibiting the activation of prothrombin, when it binds to APL antibody or anti-2GPI antibody Promotes hemagglutination, which causes thrombocytopenia due to the action of IgG-type APL antibody on phosphatidylserine (PTC) located on the inner side of the platelet membrane. When platelets are activated, PTC is exposed and binds to APL antibody to destroy platelets. Aggregation, APL antibody can also bind to PTC of red blood cells to cause hemolytic anemia. In addition, the effect of APL antibody on endothelial cells, prostacyclin and cross-reactivity with complement receptors, cell surface adhesion molecules, etc., may also be pathogenesis. a part of.
Prevention
Antiphospholipid antibody syndrome prevention
1. Early diagnosis and treatment must be done.
2. On a regular basis, you should maintain the law of life, feel comfortable, pay attention to exercise, and actively cooperate with treatment.
Complication
Antiphospholipid antibody syndrome complications Complications, intracranial venous sinus thrombosis, epilepsy dementia
If the lower extremity arterial embolization can occur intermittent claudication or gangrene, central nervous system involvement can also have cerebral venous sinus thrombosis, chorea, epilepsy, multiple sclerosis dementia, about 36% of primary antiphospholipid antibody syndrome and 48% of anti-phospholipid antibody syndromes with systemic lupus erythematosus have heart valve disease, and occasionally small intestinal infarction and hemorrhage, microangiopathic pancreatitis have been reported.
Symptom
Antiphospholipid antibody syndrome symptoms Common symptoms Nodular skin necrosis Dementia Hypertension Fetal growth retardation Cerebral ischemia Valve leaflet thickening Intermittent abortion Intravascular Coagulation
Thrombosis
Thrombosis is the most important clinical manifestation of antiphospholipid antibody syndrome. Thrombosis can occur in any part of the body. It is often involved in peripheral blood vessels, cerebrovascular and blood vessels of the heart, lungs, kidneys, etc. There is no significant relationship between the occurrence of thrombus and the change of serum antiphospholipid antibody titer, but sometimes the formation of large thrombus is often accompanied by a decrease in antibody titer.
(1) Peripheral blood vessels: Venous thrombosis is the most common symptom of antiphospholipid antibody syndrome, which occurs in deep veins and superficial veins of lower extremities. The superficial vein thrombosis of lower extremities often manifests as thrombophlebitis, and peripheral vascular artery embolism is not common. If the lower extremity arterial embolization can occur intermittent claudication or gangrene.
(2) Central nervous system: The anti-phospholipid antibody syndrome of arterial thrombosis mainly involves the cerebral arteries, among which the middle cerebral artery involvement is the most common, mainly manifested as a sudden stroke, without any prodromal symptoms, most stroke patients It can be associated with valvular disease and reticular plaque of the skin. Clinical, imaging, and cerebrospinal fluid examinations often show in situ thrombosis rather than embolism or hemorrhage. A small number of patients can also cause brain damage from emboli of heart valve sputum. Due to embolization, stroke of antiphospholipid antibody syndrome is often recurrent, and the presence of antiphospholipid antibodies is a risk factor for stroke. Studies have shown that after the first stroke, antiphospholipid antibody-positive patients have another stroke. The rate is 8 times higher than that of antiphospholipid antibody-negative patients. Another common symptom of central nervous system involvement is transient cerebral ischemic attack (TCIA), which may be caused mainly by small blood vessel obstruction. CT scan is generally No abnormal findings, but magnetic resonance imaging revealed a small area of T1, increased T2 signal, and involvement of the central nervous system. His performance as well as cerebral venous sinus thrombosis, chorea, epilepsy, multiple sclerosis, dementia and so on.
(3) Heart: The most common involvement of mitral and aortic valve, 36% of primary antiphospholipid antibody syndrome and 48% of anti-phospholipid antibody syndrome with systemic lupus erythematosus have heart valve disease, the main performance There are: valvular leaflet thickening, thrombotic neoplasm, mitral regurgitation and stenosis, epidemiological investigations show that about 6% of patients with primary antiphospholipid antibody syndrome die from congestive heart failure (mainly by two Due to regurgitation, it has recently been found that patients with antiphospholipid syndrome have a linear deposition of IgG-type anticardiolipin antibodies in the lower layer of heart valve endothelial cells, which may provide important explanations for the mechanism of heart valve disease in antiphospholipid syndrome. Clues, other manifestations of cardiac involvement, and coronary artery occlusion can lead to myocardial infarction, but the incidence of myocardial infarction with antiphospholipid syndrome is much lower than that of cerebral infarction, and the presence of antiphospholipid antibodies is not induced again. An independent risk factor for myocardial infarction. In addition, patients with antiphospholipid syndrome may have intraluminal (mainly left atrial and left ventricular) thrombosis, acute and chronic cardiomyopathy. Performance, the further development of cardiomyopathy may cause heart failure.
(4) Lung: mainly manifested as pulmonary embolism and pulmonary infarction. Repeated thromboembolism can lead to pulmonary hypertension. In addition, pulmonary microthrombus formation and intra-alveolar hemorrhage can be seen.
(5) Kidney: thrombosis of small renal blood vessels is common, early damage can be asymptomatic, generally manifested as proteinuria, moderate proteinuria is the most common clinical symptom, and can last for a long time, can also appear high renal Blood pressure, generally no hematuria and hypocomplementemia, long-term renal damage can develop into renal insufficiency, antiphospholipid antibody syndrome is associated with systemic lupus erythematosus, renal biopsy is required to identify kidney damage is caused by lupus nephritis Still caused by a blood clot.
(6) Skin: Reticulated bleu is one of the common symptoms of antiphospholipid antibody syndrome. Other manifestations of skin damage include skin ulcers, erythema, painful purpura and bloody blisters, and sometimes extensive skin necrosis. .
(7) Other manifestations: antiphospholipid antibody syndrome may have ocular damage, manifested as obstruction of retinal blood vessels, causing ischemia and necrosis of the retina, and may also have optic neuritis, etc., a few patients may have liver damage, such as Budd -Chiari syndrome, hepatic nodular hyperplasia, hepatic necrosis, increased liver enzymes (caused by occlusion of small veins) and portal hypertension, and occasionally reported small infarction and hemorrhage, microangiopathic pancreatitis.
(8) Severe antiphospholipid antibody syndrome: refers to a small number of patients with small blood vessels or large and small blood vessels in a short period of time (usually within a few days to weeks), resulting in extensive thrombosis, causing ischemia and Necrosis, also known as catastrophic anti-phospholipid syndrome (CAPS), in some cases, viral infection or allergy may be the cause of this severe antiphospholipid antibody syndrome, but most severely resistant There is no aura in the occurrence of phospholipid antibody syndrome. Patients generally have elevated white blood cells, elevated serum levels of various tissues and extensive intravascular coagulation. For some patients, antiphospholipid antibodies often drop before severe antiphospholipid antibody syndrome. The degree is high, but it is often negative at the time of onset and within a few months after the onset. Severe antiphospholipid antibody syndrome is generally prone to death.
2. Pregnancy performance
About half of pregnant women with antiphospholipid syndrome may have miscarriage. Abortion usually occurs in the middle and late pregnancy, mainly due to the decrease of placental function due to placental vascular thrombosis and placental infarction. The relationship between abortion and IgG antiphospholipid antibody Closely, the incidence of abortion in IgM and IgA antiphospholipid antibody-positive patients is extremely low. Other manifestations of antiphospholipid antibody syndrome during pregnancy include: pre-eclampsia, pregnancy-induced hypertension, fetal growth retardation, fetal distress and preterm birth, etc. The incidence of these is about 30%, these clinical manifestations are prone to aggravation during pregnancy, a small number of non-antiphospholipid antibody syndrome serum high titer of IgG antiphospholipid antibodies can increase the risk of miscarriage, but whether it causes other The increase in complications of obstetrics and gynecology is still unclear, and most pregnant women with non-antiphospholipid antibody syndrome, although serum anti-phospholipid antibodies are positive, but the clinical complications have not increased significantly, and can be normal pregnancy.
3. Thrombosis
Patients with antiphospholipid antibody syndrome often show moderate thrombocytopenia (generally >50×109/L). Although antiphospholipid antibody syndrome has thrombocytopenia, it is still prone to thrombosis, few bleeding symptoms, systemic erythema Common thrombocytopenia in lupus is associated with the presence of antiphospholipid antibodies. About 40% of patients with systemic lupus erythematosus-positive anti-phospholipid antibodies may have thrombocytopenia, but only 10% of anti-phospholipid antibody-negative systemic lupus erythematosus has thrombocytopenia. Conversely, 70% to 80% of patients with systemic lupus erythematosus with thrombocytopenia are positive for antiphospholipid antibodies.
4. Children's antiphospholipid antibody syndrome
Children's antiphospholipid antibody syndrome is more common in women (the ratio of male to female is about 2:3), and the age of onset is 8 months to 16 years (average 10 years). Most children are prone to recurrent thrombosis, arteriovenous The thrombus ratio is 1:0.6, and about 14% of patients can have arteriovenous thrombosis at the same time, but younger children are more likely to form arterial thrombosis than older ones. Among them, cerebral arterial thrombosis is more common, compared with adults. Children with pulmonary embolism are less common.
Examine
Examination of antiphospholipid antibody syndrome
1. Syphilis serum false positive test (BFP-STS) and VDRL test
The positive rate of BFP-STS test in lupus or other connective tissue diseases is 5% to 19%. The main antigen components of the two tests are a mixture of cardiolipin, phosphatidylcholine (lecithin) and cholesterol, thus for thrombosis. The sensitivity and specificity of the two test methods are not high.
2. Lupus anticoagulant (LA)
Kaolin agglutination time (KCT) is a more sensitive method in the LA screening test and is of great significance for the detection of LA substances during pregnancy.
3. Antiphospholipid antibody, anticardiolipin antibody
APL antibodies such as LA, ACL antibodies, etc., have a higher clinical significance when the titer is high. Several international standardization workshops have developed a unified ELISA method for the detection of APL, which can be used for APL IgG, IgA, IgM. For quantitative or semi-quantitative determination, it is now recommended to express APL results with negative, low, medium, and high positives to improve the consistency and repeatability of test results in each laboratory.
CT scans generally have no abnormal findings, but magnetic resonance imaging can detect small areas of T1 and T2 signals.
Diagnosis
Diagnostic identification of antiphospholipid antibody syndrome
Antiphospholipid antibody syndrome often has multiple clinical manifestations. Unexplained venous thrombosis is the most common symptom of antiphospholipid antibody syndrome, but tumor, oral contraceptive, nephrotic syndrome, thrombocytopenia, antithrombin III deficiency , protein C deficiency, protein S deficiency, abnormal fibrinogenemia, polycythemia, paroxysmal nocturnal hemoglobinuria and urinary homocysteinemia can cause thrombosis, need to be identified during diagnosis, anti- The thrombosis of phospholipid antibody syndrome is reproducible, but each time it is usually a single thrombus, which is emitted in different blood vessels. The interval between repeated episodes is often several months to several years. A few severe antiphospholipid antibody syndromes are short-lived. Extensive intravascular coagulation occurs in combination with sepsis, thrombotic thrombocytopenic purpura and DIC. Another common symptom of antiphospholipid syndrome is recurrent miscarriage, and many patients may be diagnosed as resistant to abortion as initial performance. Phospholipid antibody syndrome, but abortion is one of the common diseases in obstetrics and gynecology, many other factors can be caused, must be added Except, such as uterine abnormalities, other systemic diseases, chronic infections and genetic abnormalities and other factors.
