Antiphospholipid syndrome and kidney damage

Antiphospholipid syndrome (AFS) is a clinico-laboratory symptom complex associated with the synthesis of antibodies to phospholipids (aFL) and characterized by venous and / or arterial thrombosis, habitual miscarriage, thrombocytopenia. For the first time the disease of antiphospholipid syndrome was described by G. Hughes in 1983 in patients with systemic lupus erythematosus, and in the late 90s of the XX century he was called "Hughes syndrome" in recognition of the role of the scientist in studying this pathology.

[1], [2], [3], [4], [5], [6]

Epidemiology

Antiphospholipid syndrome, like systemic lupus erythematosus, develops mainly at a young age, in women 4-5 times more often than in men, but recently there has been a tendency to increase the incidence of the latter by the primary antiphospholipid syndrome. The true prevalence of antiphospholipid syndrome in the population has not yet been fully established. The frequency of detection of antibodies to phospholipids in healthy people is on the average 6 (0-14)%, however, their high titer associated with the development of thromboses is recorded in less than 0.5% of healthy individuals.

In women with recurrent obstetric pathology, these antibodies detect in 5-15% of cases. In patients with systemic lupus erythematosus, the frequency of detection of antibodies to phospholipids averages 40-60%, nevertheless the clinical manifestations of antiphospholipid syndrome develop less frequently: the incidence of thrombotic complications in patients with antibodies to phospholipids in systemic lupus erythematosus reaches 35-42%, whereas in their absence does not exceed 12%.

[7], [8], [9], [10], [11], [12], [13], [14]

Causes of the antiphospholipid syndrome

The causes of antiphospholipid syndrome are not known. The most common antiphospholipid syndrome develops with rheumatic and autoimmune diseases, mainly in  systemic lupus erythematosus. 

An increase in the level of antibodies to phospholipids is also observed in bacterial and viral infections ( streptococci  and  staphylococci, mycobacterium tuberculosis, HIV, cytomegalovirus, Epstein-Barr viruses, hepatitis C and B and other microorganisms, although thromboses rarely develop in such patients), malignant neoplasms some drugs (hydralazine, isoniazid, oral contraceptives, interferons).

Antibodies to phospholipids are a heterogeneous population of antibodies to antigenic determinants of negatively charged (anionic) phospholipids and / or to phospholipid-binding (cofactor) plasma proteins. To the family of antibodies to phospholipids include antibodies, which determine the false positive reaction of Wasserman; lupus anticoagulant (antibodies that prolong in vitro clotting time in phospholipid-dependent coagulation tests); antibodies reacting with cardiolipin AFL and other phospholipids.

[15], [16], [17], [18]

Symptoms of the antiphospholipid syndrome

Symptoms of antiphospholipid syndrome differ significantly in variety. Polymorphism of clinical manifestations is determined by the localization of thrombi in veins, arteries or small intragonal vessels. As a rule, thromboses recur either in the venous or in the arterial bed. The combination of thrombotic occlusion of peripheral vessels and vessels of the microcirculatory bed forms a clinical picture of multi-organ ischemia leading to multiple organ dysfunction in some patients.

[19], [20], [21], [22], [23], [24], [25]

Forms

At present, secondary antiphospholipid syndrome is associated with predominantly systemic lupus erythematosus, and primary, developing in the absence of any other disease and, apparently, is an independent nosological form. A special variant of the antiphospholipid syndrome is considered to be catastrophic, caused by acute thrombococclusive lesions of mainly the vessels of the microvasculature of vital organs (at least three simultaneously) with the development of multiple organ failure in the period from several days to several weeks. The primary antiphospholipid syndrome accounts for 53%, for the secondary - 47%.

[26], [27], [28], [29], [30], [31]

Diagnostics of the antiphospholipid syndrome

Characteristic signs of antiphospholipid syndrome are thrombocytopenia, usually moderate (the number of platelets is 100 000-50 000 in 1 μl) and not accompanied by hemorrhagic complications, and Coombs-positive hemolytic anemia. In a number of cases, a combination of thrombocytopenia with hemolytic anemia (Evans syndrome) is noted. In patients with nephropathy associated with antiphospholipid syndrome, especially with catastrophic antiphospholipid syndrome, Coombs-negative hemolytic anemia (microangiopathic) may develop. In patients with the presence of lupus anticoagulant in the blood, lengthening of activated partial thromboplastin time and prothrombin time is possible.

[32], [33], [34], [35], [36], [37], [38], [39]

Treatment of the antiphospholipid syndrome

Treatment of antiphospholipid syndrome and kidney damage is not clearly defined, since there are no large controlled comparative studies to date assessing the effectiveness of different regimens for this pathology.

• In the treatment of patients with secondary antiphospholipid syndrome within the framework of systemic lupus erythematosus, glucocorticoids and cytostatic drugs are used in doses determined by the activity of the disease. Suppression of the activity of the underlying disease, as a rule, leads to the disappearance of signs of antiphospholipid syndrome. In the primary antiphospholipid syndrome, glucocorticoids and cytotoxic drugs are not used.
• Despite the fact that treatment with glucocorticoids and cytostatic drugs leads to the normalization of the titre of AFL and the disappearance of lupus anticoagulant in the blood, it does not eliminate hypercoagulation, and prednisolone even strengthens it, which preserves the conditions for recurrence of thromboses in various vascular pools, including in the vascular bed kidney. In this regard, in the treatment of nephropathy associated with antiphospholipid syndrome, it is necessary to appoint anticoagulants in the form of monotherapy or in combination with antiaggregants. Eliminating the cause of kidney ischemia (thrombotic occlusion of the intracranial vessels), anticoagulants are able to restore renal blood flow and lead to improved renal function or inhibit the progression of renal failure, which, however, requires confirmation in studies evaluating the clinical efficacy of both direct and indirect anticoagulants in patients antiphospholipid syndrome-associated nephropathy.