Antiphospholipid syndrome – symptoms, diagnosis and kidney problems
With the term antiphospholipid syndrome the combination of antiphospholipid antibodies and clinical manifestations of arterial and venous thrombosis, habitual abortions (because of placental thrombosis) and thrombocytopenia is described. These are the main symptoms of the antiphospholipid syndrome.
In addition in some patients may occur the following: purple rash on the limbs similar to islands which is because of dermal microthrombosis (livedo reticularis), hemolytic anemia, headache (migraine), epilepsy, and endocarditis (according the type of Libman – Sacks).
Antiphospholipid antibodies are a heterogeneous family of antibodies directed against anionic phospholipids or proteins – phospholipids complexes which are found in autoimmune diseases, infectious diseases and others. Any vascular bed can be affected when there is antiphospholipid syndrome, but the venous thrombosis of lower limbs are most commonly met, and more rarely – of the retina, renal and hepatic veins. The arterial thromboses in the central nervous system lead to anemic infarctions or fleeting ischemic crises.
The diagnosis of antiphospholipid syndrome is based on the clinical symptoms and the moderate to high titers of anticardiolipins and/or lupus antibodies and false-positive serologic tests for syphilis. These antibodies can be associated with a systemic connective tissue disease, or could be found in isolation. In many patients with antiphospholipid syndrome can be found antibodies against β2 – glycoprotein-l, anti-mitochondrial antibodies, anti – endothelial, anti – platelet, anti – erythrocyte, etc.
Kidney problems in antiphospholipid syndrome
Involvement of the kidneys can be met in one quarter of the patients with antiphospholipid syndrome. In most of the cases it is combined with arterial hypertension which complications (for example cerebral haemorrhage) usually turn out to be the natural cause of death. The histopathological examination with them shows microtrombosis of glomerular capillaries and renal arterioles, with no evidence of active glomerulonephritis. Besides this thrombotic microangiopathy, thrombotic diathesis includes renal vein thrombosis, renal infarction or stenosis, reversible ischemic acute renal failure, increased incidence of thromboses in the transplanted kidneys and reduced survival of recipients. The combination of transition vessels thrombosis with thrombotic microangiopathy suggest two pathogenetic mechanisms of injury in the antiphospholipid syndrome: one associated with impaired coagulation, and the other – with immune damage of endothelial cells. Whatever the thrombotic changes are, they do not cover the probable spectrum of this pathology, in which the kidney damages can be the direct result of an immune conflict (glomerulonephritis). The first message in support of this possibility is of a focal proliferative glomerulonephritis without glomerular thrombosis in a 10-year-old child with antiphospholipid syndrome. Later is described a combination of initial antiphospholipid syndrome (with an amputation of the leg because of gangrene) with IgA-glomerulonephritis and membranous glomerulonephritis. Differential diagnostic problems arise in the cases of glomerulonephritis in a secondary antiphospholipid syndrome (lupus erythematodes disseminatus), since in these cases it is difficult to assess whether the renal damage is in a result of collagenous disease. In such cases, the leading role is given to the collagenous disease and the antiphospholipid syndrome is considered as a background state.
Pulmonary pathology in antiphospholipid syndrome
Pulmonary manifestations of antiphospholipid syndrome include multiple embolism, thrombosis of the pulmonary artery or microthrombosis (with or without capilliaritis), pulmonary hypertension, fibrosing alveolitis and alveolar hemorrhage. The presence of antiphospholipid antibodies is not usually associated with hemorrhagic events and when they are present although that in patients with antiphospholipid syndrome, then diathesis is due to the lack of any procoagulant factor, of the severe thrombocytopenia or because of the presence of severe renal failure or liver disease. Clinically they are represented by respiratory distress syndrome of adults (dyspnea, fever, and radiologically – pulmonary infiltrates).
An example of a combination of lung and kidney problems in antiphospholipid syndrome
The case of a 36-year old woman is described, who died of multi organ failure, with evidence of initial antiphospholipid syndrome - progressive weakness, anemia, preceding venous thrombosis of the leg, prolonged oral anticoagulant therapy, two full pregnancies in the past, polyarthralgia) and semilunar glomerulonephritis ( enhanced creatine values, severe proteinuria, hematuria and hyaline cylinders in the urine). She has developed progressive respiratory failure, with streaks of blood in the sputum, fever, decreased urine quantity and generalized edemas. The antinuclear antibodies were positive at a titre 1 / 200, as well as in the direct Coombs test. Immunological tests for SLE and ANCA were negative, the serum levels of C3 and C4 were normal. After her death it was documented that there were positive titers of IgG antiphospholipid antibodies (sixfold increase), whereas IgM antiphospholipid bodies were negative. Lupus anticoagulant was also positive. Later positive titers of the serum ß2-glycoprotein-I antibodies (cofactor of the antiphospholipid antibodies) were established. During the autopsy thrombotic microangiopathy in the kidneys, intestines, pancreas, spleen, adrenal glands, thyroid, muscles, lungs and heart, with micro infarctions were established. Thrombophlebitis of the lower limbs and non-infectious mitral valve endocarditis were also found. 87% of the glomerulus in the kidneys was involved by the semilunar with different degrees of maturity. Immunofluorescent study of necropsy material from the kidney (no specified time limit after death) was conducted. The results were negative regarding the C3, S1q, IgA and IgM, with traces of fibrin in some semilunars. Electro microscopically in the glomerulus, dense deposits were not detected (immune complexes). Evidence of acute and chronic focal pneumonia and picture of the so called ”shock lungs” were found in the lungs. The pathogenesis of the antiphospholipid syndrome is associated with activation of endothelium and secondary – of blood monocytes, provoked by the antiphospholipid antibodies.