Antiphospholipid Antibody Syndrome
The "Anti-phospholipid Antibody" Syndrome (APA Syndrome) is a clinical condition associated with the predisposition to arterial and venous thrombosis, and to recurrent spontaneous abortions, characterized by thrombocytopenia and the presence in the circulation of particular antibodies, called antiphospholipids.
Anti-phospholipid antibody syndrome can arise in an isolated manner (primitive form, therefore without clinical evidence of association with other autoimmune diseases) or afflict patients with systemic autoimmune diseases (secondary form); it is, for example, quite widespread in the presence of systemic lupus erythematosus (in about 30-50% of cases), and to a much lesser extent in patients with systemic sclerosis, rheumatoid arthritis, Behçet's disease, Crohn's disease, malignant tumors and infections (for example HIV infection). In addition, it can occur after taking some medications.
Antiphospholipid antibodies
Antiphospholipid antibodies (aPL) are a heterogeneous group of autoantibodies directed against negatively charged molecules and towards a combination of phospholipids and plasma proteins. They are divided into three classes: anticardiolipin (aCL), antibeta2glycoprotein1 (antiβ2GPI) and lupus anticoagulant (LAC). Their antibody action is directed against various combinations of phospholipids, high affinity proteins for phospholipids or phospholipid-protein complexes. In vitro Lac acts as an inhibitor of coagulation (anticoagulant), a fact demonstrated by the lengthening of the coagulation time in phospholipid-dependent hemocoagulation tests, but paradoxically in vivo it favors a displacement of the coagulative equilibrium in a pro-thrombotic sense (greater tendency to coagulation ). This is to emphasize that the exact mechanism by which these antibodies predispose to thrombosis is still uncertain.
NOTE: the prevalence of antiphospholipid antibodies in the healthy population varies from one to 5% and is considered greater in the elderly. It is not yet clear whether these subjects are at greater risk of developing thrombotic events or pregnancy complications. It is however believed that the accidental detection of low titre antiphospholipid antibodies entails a minimal risk of thrombosis, while the probabilities increase if these antibodies are present at high titre. It is known that in subjects who are positive for aPL who have had thrombosis, the risk of recurrence is higher than that of negative subjects; the same applies to abortions. Other studies have shown that 50 to 70% of patients with systemic lupus erythematosus and anti-phospholipid antibody experience a thrombotic syndrome during a 20-year follow-up. These epidemiological studies are very important, because they allow to reduce the thrombotic risk for prophylactic purposes; this result is obtained through the chronic use of anticoagulant and / or antiplatelet agents, avoiding the use of estrogens (including the contraceptive pill), high-dose steroids, alcohol and smoking, and combating hyperlipidemia with the diet, physical activity or possibly through the use of specific drugs such as statins, fibrates and megadoses of niacin.
Clinical manifestations
The thrombotic events that characterize the Anti-phospholipid antibody syndrome can affect arteries, veins or capillaries, and involve any organ or apparatus. Let us briefly recall how a thrombus is a lump, a blood clot that forms in the circulatory system and can grow to the point of using the blood vessel in which it originates; moreover, the thrombus can fragment, giving rise to emboli of a smaller size that - pushed towards the periphery by the blood - can completely or totally occlude smaller caliber vessels, reducing the blood supply of the downstream tissues. In the antiphospholipid syndrome the vascular occlusion is mainly due to the latter aspect (thromboebolism).
The main manifestation of arterial type is the ischemic cerebral stroke, often preceded by transient cerebral ischemic attacks; other times there is occlusion of visceral or peripheral arteries and myocardial infarction.
The main manifestation of venous type is deep vein thrombosis; sometimes there is thrombosis of the cerebral, renal and hepatic veins, and pulmonary embolism. Venous thromboses associated with aPL syndrome are more frequent and less severe than arterial ones.
Peculiarities of the antiphospholipid antibody syndrome are also pregnancy complications, with recurrent spontaneous abortions, fetal growth retardation and premature births due to severe pre-eclampsia or severe eclampsia, or severe placental insufficiency.
Symptoms
The clinical picture of the antiphospholipid antibody syndrome is very varied and depends on the possible onset of associated clinical manifestations, the symptoms of which are related to the location and extent of thrombosis. In fact, since thromboses can occur anywhere, the symptoms and signs that result can be the most variable, practically involving all medical specialties: in this regard, the following articles can be consulted: stroke symptoms; myocardial infarction symptoms; venous thrombosis symptoms; pulmonary embolism symptoms. Clinical pictures can vary from mild manifestations, characterized by superficial thrombophlebitis, to more serious ones, such as the so-called catastrophic syndrome caused by antiphospholipid antibodies, in which the multiple district dissemination of thrombuses seriously endangers the patient's life.
Diagnosis
The currently accepted diagnostic criteria for the definition of the syndrome are the so-called "Sapporo Criteria", established by an international group of experts in 1999. The diagnosis of APA Syndrome requires the presence of at least one of the following clinical criteria and a laboratory, independently of the time interval between the clinical event and the laboratory data:
| CLINICAL CRITERIA | CRITERIA LABORATORISTICS |
1. Vascular thrombosis: one or more episodes of arterial, venous or microcirculatory thrombosis, in any tissue or organ. Thrombosis must be confirmed by imaging, doppler or histopathology, with the exception of superficial venous thrombosis. For histopathological confirmation, thrombosis must be present without significant evidence of inflammation of the vascular wall. | 1. Positivity (high or moderate titre) for anticardiolipin IgG or IgM antibodies found on two or more occasions at a distance of at least 6 weeks, measured with an ELISA test standardized for anticardiolipin antibodies β2 - glycoprotein I - dependent. |
2. Obstetric pathology: - one or more deaths of morphologically normal fetuses of unknown cause at or beyond the 10th week of pregnancy. Normal fetal morphology must be documented by ultrasound or direct examination of the fetus; or - one or more premature births of morphologically normal newborns on or before the 34th week of pregnancy, due to severe pre-eclampsia or eclampsia, or severe placental insufficiency; or - three or more consecutive spontaneous abortions due to an unknown cause before the 10th week of pregnancy, with the exclusion of maternal anatomical or hormonal abnormalities or paternal or maternal chromosomal causes. | 2. Positivity for LAC diagnosed according to the SSC - ISTH criteria, found on two or more occasions at least 6 weeks apart: - Extension of at least one phospholipid-dependent coagulation test (screening test). - Evidence of inhibitory activity demonstrated by the effect of patient plasma on a pool of normal plasmas - Evidence that the inhibitory activity is dependent on phospholipids (confirmation test) - Exclusion of other coagulopathies |
Therapy
To learn more: Drugs for Anti-phospholipid Antibody Syndrome
Treatment of Antiphospholipid Antibody Syndrome does not differ from that listed for prophylaxis of thrombotic events in patients with high levels of these antibodies in the blood. It is therefore essentially based on the chronic use of dicumarolic anticoagulants, such as sintrom or coumadin, so as to bring the INR of the prothrombin time between 2.5 and 3.5, or of platelet anti-aggregates such as acetylsalicylic acid and the clopidogrel. In the acute phase, elective anticoagulants are represented by heparins of various molecular weight. In the case of a catastrophic syndrome caused by antiphospholipid antibodies, the plasma exchange rate and the joint use of inussopressor drugs and immunoglobulin boluses is expected.
