Levels Of Antiphospholipid Antibodies Research Articles

Disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system in systemic lupus erythematosus

Increased thrombogenesis observed in systemic lupus erythematosus (SLE) is derived from multiple mechanisms, including: Enhanced coagulation factor VIII:VWf activity, lupus anticoagulants, anti-phospholipid antibodies, acquired deficiencies of natural anti-thrombotic mechanisms (protein C, protein S, anti-thrombin III), and impaired fibrinolytic mechanisms. We studied the fibrinolytic mechanisms of 18 patients with systemic lupus erythematosus, selected carefully to avoid other possible causes of abnormalities in the fibrinolytic activity. Despite the fact that the euglobulin lysis time in steady state was normal in all instances, disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system were found in all SLE patients: TPA activity was undetectable in all cases, whereas it was above 0.4 IU/ml in a control group. In 72 percent of patients, the undetectable TPA activity was correlated with abnormally high PAI activity; PAI levels were normal in all members of the control group, their mean value being 0.74 versus 8.63 IU/ml for SLE patients (P less than .01). Coagulation protein C deficiency was found in 3 patients (17%). Even though within normal range, fibrinogen levels were significantly higher in SLE than in normal controls (219 versus 192 mg/dl, P less than .01) and plasminogen levels were significantly higher in SLE than in controls (117 versus 78.2%, P less than .01). Cross-linked fibrin derivatives (D-D dimers) were negative in all patients with SLE. Sixty-eight percent of SLE patients had high levels of antiphospholipid antibodies, but no correlation with the disturbances of the TPA/PAI system was found. It is concluded that most patients with SLE display severe abnormalities in the TPA/PAI anti-thrombotic system and that these abnormalities may be related to the lupus thrombophilia, apparently multifactorial in its origin.

Repeated Intestinal Ulcerations in a Patient With Systemic Lupus Erythematosus and High Serum Antiphospholipid Antibody Levels

We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered.

MALIGNANT HYPERTENSION AND ANTIPHOSPHOLIPID ANTIBODIES AS PRESENTING FEATURES OF SLE IN A YOUNG WOMAN USING ORAL CONTRACEPTIVES

A 24-year-old woman developed malignant hypertension while on oral contraceptives (OCs). She was found to have incomplete systemic lupus erythematosus (SLE) with DNA antibodies and high levels of antiphospholipid antibodies (APLA). She later developed SLE and has had three miscarriages and a cerebellar infarction.

Oral Contraceptives in Systemic Lupus Erythematosus: Side-effects and Influence on the Activity of SLE

The risk of a disease flare-up and the side-effects experienced during the use of oral contraceptives (OCs) were studied in 85 female SLE patients, 18-44 years old, regularly attending two specialist rheumatological clinics. Thirty-one patients had used combined oral contraceptives (cOCs) during or after the onset of SLE. Initial manifestations or exacerbations of SLE were noted in 4 (13%) of these patients during the first six months after starting cOCs and three of these four patients had major renal involvement. The incidence of disease flare-ups was the same as in patients not using cOCs. Two patients developed deep venous thrombosis during cOCs, and they both had antiphospholipid antibodies. Thirty-two patients had used progestagen-only contraceptives (PCs) and they were discontinued in 25 (78%) of the patients because of minor side-effects, mainly reflecting poor gynaecological tolerance. Albeit there is no definitive proof that cOCs actually precipitate or exacerbate SLE some patients may be more likely to have adverse effects while taking cOCs. It appears best to avoid cOCs in SLE patients with high levels of antiphospholipid antibodies and in patients with active nephritis. PCs cause many side-effects in SLE patients, but do not seem to activate the disease.

Prevalence of High Levels of Antiphospholipid Antibodies in Otherwise Unexplained Juvenile Venous Thromboembolism

Prevalence of High Levels of Antiphospholipid Antibodies in Otherwise Unexplained Juvenile Venous Thromboembolism

Association between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus

purpose: Although the antiphospholipid antibodies are well recognized to be associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies and cardiac abnormalities in patients with SLE. patients and methods: A total of 75 consecutive SLE patients and 60 healthy sex- and age-matched control subjects were evaluated in a case-control study. All participants underwent M-mode, two-dimensional, and Doppler echocardiography. Antiphospholipid antibodies levels were assayed in each patient. The prevalence of antiphospholipid antibodies in patients with and without echocardiographic abnormalities was compared. results: Compared with the control group, SLE patients had significantly more pericardial abnormalities, left ventricular hypertrophy, left atrial enlargement, left ventricular dysfunction and verrucous valvular thickening, global valvular thickening with dysfunction, and mitral and aortic regurgitation. Among these abnormalities, antiphospholipid antibodies were significantly associated with isolated left ventricular (global or segmental) dysfunction (four of five positive; p <0.05), verrucous valvular (mitral or aortic) thickening (seven of nine positive; p <0.005), global valvular (mitral or aortic) thickening and dysfunction (five of six positive; p <0.02), as well as mitral regurgitation (16 of 19 positive; p <0.001) and aortic regurgitation (five of six positive; p <0.02). conclusion: Valvular lesions and myocardial dysfunction are associated with elevated antiphospholipid antibodies. This study has important implications for the pathogenic role of antiphospholipid antibodies in relation to these cardiac abnormalities.

Pathophysiology of antiphospholipid antibodies: Absence of prostaglandin-mediated effects on cultured endothelium

Antiphospholipid antibodies are associated with recurrent pregnancy loss and thrombosis. Studies suggest that antiphospholipid antibodies may inhibit the production of prostacyclin by vascular tissues. We incubated sera from women with moderate to high levels of antiphospholipid antibodies with primary human umbilical vein endothelial cell cultures. Intact confluent, subconfluent, hydrogen peroxide-damaged, and mechanically damaged endothelial cell monolayers were evaluated for the production of the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in the presence of sera that were positive and negative for antiphospholipid antibodies. All sera were assayed for baseline concentrations of 6-keto-prostaglandin F1 alpha before incubation with endothelial monolayers. Additionally, the extent of binding of antiphospholipid antibodies to intact and damaged endothelium was studied by immunofluorescent techniques and enzyme-linked immunosorbent assay. Our results indicate that prostacyclin production is not impaired by sera containing antiphospholipid antibodies, regardless of the condition of the endothelium. Further, we were unable to demonstrate binding of immunoglobulin from sera containing antiphospholipid antibodies to intact or damaged endothelium. However, the baseline concentration of 6-keto-prostaglandin F1 alpha was nearly fourfold higher in sera containing antiphospholipid antibodies. The finding of elevated baseline serum concentrations of prostacyclin metabolite in patients with antiphospholipid antibodies suggests a condition of long-term stimulation or altered metabolism of prostacyclin.

Renal artery thrombosis and hypertension in a 13 year old girl with antiphospholipid syndrome.

The case of a 13 year old girl with renal artery thrombosis and hypertension is described. A cerebrovascular accident and a probable occlusion of the superior mesenteric artery also occurred. Very high levels of 'lupus anticoagulant', anticardiolipin antibodies as well as false positive Venereal Disease Research Laboratory tests were repeatedly shown. Moreover, the patient fulfilled at least four classification criteria for systemic lupus erythematosus, but only a slight positivity for antinucleolar antibodies was present. The striking relation between antiphospholipid antibody levels and clinical events and the treatment of this complex syndrome are discussed.

Primary antiphospholipid syndrome: features of patients with raised anticardiolipin antibodies and no other disorder.

Raised levels of serum antiphospholipid antibodies have most commonly been reported in patients with systemic lupus erythematosus (SLE). There remains, however, a group of patients with raised antiphospholipid antibody levels who do not have any other well defined disease, but do have clinical features associated with these raised antibodies. The clinical, haematological, and serological features of 20 such patients are reported. Antiphospholipid antibody levels were measured by a solid phase assay for anticardiolipin activity. Fourteen patients had raised IgG antiphospholipid antibodies, 12 had raised IgM, and six had both. Nine out of 19 had raised antinuclear antibody levels; however, non fulfilled criteria for the diagnosis of SLE. Seven patients had a history of venous thrombosis and five of definite or presumed arterial thrombosis-for example, stroke. Of the 15 female patients who underwent pregnancy, 12 experienced fetal loss with up to eight abortions each (mean 3.6). Six individuals had thrombocytopenia and four others had migraines. Other clinical features included livedo reticularis, cardiac and neuropsychiatric disorders, arthralgias, and Raynaud's phenomenon. These findings confirm that the clinical features of individuals with what may be called the 'primary antiphospholipid syndrome' are similar to those in patients with other diagnoses who have raised antiphospholipid antibodies. They indicate that the antiphospholipid syndrome may be related to SLE and other autoimmune diseases, but that, although it frequently overlaps with these disorders, it also exists as a distinct entity.

Amaurosis fugax associated with antiphospholipid antibodies

In more than 50% of amaurosis fugax patients under 45 years of age no cause for the episodes of visual loss is identifiable. We have encountered 6 young adults (4 women and 2 men) with episodes of amaurosis fugax associated with elevated levels of antiphospholipid antibodies. Splinter hemorrhages of the nail beds were present in most patients. Treatment with antiplatelet medications and anticoagulants appeared to reduce the frequency of episodes and might prevent central retinal artery occlusions or stroke.