Elevated Levels Of Anticardiolipin Antibodies Research Articles

Bilateral retinal hemorrhages after sequential endovascular treatment of bilateral unruptured cerebral aneurysms.

To report a case of bilateral retinal hemorrhages in a patient undergoing two separate endovascular interventions for bilateral cerebral aneurysms. A comprehensive ophthalmic examination was performed after the patient underwent each of two separate endovascular interventions for bilateral cerebral aneurysms. Multimodal imaging including widefield pseudocolor fundus photography, optical coherence tomography, and widefield fluorescein angiography (FA) was obtained. A systemic workup including genetic testing and hypercoagulability studies was performed. Dilated fundus examination revealed new visually significant ipsilateral retinal hemorrhages after each endovascular procedure. FA showed evidence of a peripheral retinal microangiopathy present in both eyes before the patient underwent her second endovascular procedure. Systemic workup revealed persistently elevated serum anticardiolipin IgM antibody levels at >99th percentile. Retinal complications after endovascular intracranial interventions are uncommon. This patient who developed bilateral retinal complications was found to have persistently elevated anticardiolipin antibody levels, a risk factor for thrombosis. Patients who develop retinal complications after endovascular intracranial intervention may benefit from systemic workup for hypercoagulable conditions.

Blocked mesocaval shunt with protein C deficiency in a child with extrahepatic portal hypertension

Portal vein thrombosis (PVT) is an important cause of extrahepatic portal hypertension in children. A majority of children with PVT of unknown etiology have functional protein C deficiency or abnormally elevated levels of anti-cardiolipin antibodies. We present an 8-year-old boy with portal hypertension with protein C deficiency, who underwent mesocaval shunt surgery due to recurrent episodes of bleeding esophageal varices and subsequently developed a block in the mesocaval shunt due to a thrombotic tendency.

A Case of Superior Mesenteric Artery Thrombosis Associated With Transient Elevation of Antiphospholipid Antibodies

Transient elevation of antiphospholipid antibody (APLA) is commonly observed in cases of viral infection; however, it is generally not associated with clinical thromboembolic events. In this report, we present a rare case of superior mesenteric artery (SMA) thrombosis associated with a transient elevation of APLA and discuss its relationship with fibromuscular dysplasia and adenomyosis of the uterus. Furthermore, we discuss the use of anticoagulant therapy in cases with transient elevation of APLA. In this case, a 46-year-old woman with no significant medical history was diagnosed with intestinal stenosis after SMA thrombosis that had been resolved with anticoagulant therapy. Laboratory examination showed elevated levels of anticardiolipin antibody. Resection of the stenosed ileum and hysterectomy for huge adenomyosis were performed. Anticardiolipin antibody level normalized 4 months after the operation. Anticoagulant therapy was withdrawn after anticardiolipin antibody normalized, and the patient has been free from thromboembolic events ever since. Transient elevation of APLA should be kept in mind in all patients with thromboembolic events, including those with no medical history of collagen diseases or infection. In the present case, association with fibromuscular dysplasia and adenomyosis of the uterus is suspected, but further investigation is required. Once the APLA level normalizes with the resolved thrombus, decision of withdrawing the anticoagulant therapy can be considered.

Thrombotic risk in the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPL). Patients who are diagnosed with APS are identified to have a high risk of recurrent thrombosis, which can occur despite anticoagulant therapy. The optimal type, intensity, and duration of anticoagulant therapy for the treatment of APS remain controversial issues, particularly for arterial thrombosis and recurrent thrombosis. Patients with persistently positive testing for lupus anticoagulant and elevated levels of anticardiolipin antibodies and anti-β2 glycoprotein I antibodies-known as triple positivity-appear to be at increased risk for thrombosis compared with patients who test positive for a single aPL. Recognizing that patients with APS may potentially have different thrombotic risk profiles may assist clinicians in assessing the risks, benefits, and optimal duration of anticoagulation. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.

Anti‐cardiolipin from periodontitis patients induces MCP‐1 production by human umbilical vein endothelial cells

Periodontal diseases are associated with a variety of systemic diseases, including cardiovascular disease and stroke, and patients with periodontitis demonstrate elevated levels of anti-cardiolipin antibodies. We sought to determine if anti-cardiolipin antibodies from periodontitis patients induced monocyte chemotactic protein-1 production by human vascular endothelial cells. IgG was purified from sera from 53 subjects, including chronic and aggressive periodontitis patients and periodontally healthy controls, with elevated or normal IgG anti-cardiolipin levels. In addition, anti-cardiolipin antibodies were specifically removed from some sera by immunoabsorption. We found that, irrespective of diagnostic category, IgG from subjects with elevated anti-cardiolipin induced significantly greater monocyte chemotactic protein-1 production by human vascular endothelial cells than IgG from those subjects with normal anti-cardiolipin titres. Removal of anti-cardiolipin from IgG preparations from periodontitis patients significantly reduced their ability to induce monocyte chemotactic protein-1. Since elevated titres of anti-cardiolipin are found in a significantly greater proportion of patients with periodontitis than in periodontally healthy individuals, and these antibodies activate endothelial cells to produce monocyte chemotactic protein-1, they may explain some of the associations noted between periodontal infections and systemic conditions.

Antiphospholipid-antibody-associated panniculitis

A 60-year-old man presented with intermittent, tender, erythematous nodules on the legs that were associated with mild arthralgias. He was otherwise asymptomatic but reported a history of lupus anticoagulant antibodies that were discovered incidentally on laboratory screening at the approximate time that his lesions first occurred. A biopsy specimen showed a septal and lobular panniculitis with neutrophils, histiocytes, numerous eosinophils, foci of fibrosis, and fat necrosis but no vascular pathology. An elevated activated partial thromboplastin time (PTT), appreciably elevated levels of anti-beta-2 glycoprotein I antibody (IgM and IgG), and moderately elevated levels of anticardiolipin antibody (IgM and IgG) were present. The onset and recurrence of his skin condition coincided with increased antiphospholipid antibody levels and treatment with 81 mg aspirin daily was associated with improvement.

What nephrologists need to know about antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies (aCL) and/or evidence of circulating lupus anticoagulant (LA). The kidney is a major target organ in both primary and secondary APS. With the expanding spectrum of renal diseases associated with APS, and the impact of APS in ESRD care, this subject is of increasing relevance to nephrologists. This review describes the various clinical manifestations and histological features of this syndrome, with reference to the kidney.

Evaluation of Serum Anti‐Cardiolipin and Oxidized Low‐Density Lipoprotein Levels in Chronic Periodontitis Patients With Essential Hypertension

The aim of the present study was to investigate whether chronic periodontitis caused the elevated levels of anti-cardiolipin antibodies (anti-CL) and oxidized low-density lipoprotein (oxLDL) in subjects with essential hypertension. Seventy-two subjects were categorized as healthy controls, subjects with essential hypertension and periodontal health (healthy-hypertension group), subjects with essential hypertension and gingivitis (gingivitis-hypertension group), or subjects with essential hypertension and chronic periodontitis (periodontitis-hypertension group). Individuals with essential hypertension who had been taking antihypertensive medication > or =2 years were included in the present study. The presence of supragingival plaque, bleeding on probing (BOP), probing depth (PD), and clinical attachment level were recorded, and blood samples were collected. Serum immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-CL and oxLDL levels were assessed by enzyme-linked immunosorbent assay. For IgM and IgG anti-CL assays, positive tests were defined as > or =15 IgM phospholipid units and > or =10 IgG phospholipid units, respectively. The mean IgM anti-CL level and the prevalence of subjects positive for IgM anti-CL were significantly higher in the periodontitis-hypertension group compared to the other groups (P = 0.001). No significant differences were observed in the mean IgG anti-CL and oxLDL levels or in the number of subjects positive for IgG anti-CL and positive for IgM or IgG anti-CL among the study groups. The Pearson correlation analysis revealed positive correlations between IgM anti-CL levels and supragingival plaque, BOP, and PD scores. Chronic periodontitis might play a causal role in the elevated serum levels of anti-CL antibodies in individuals with essential hypertension. These elevated anti-CL levels that are due to chronic periodontitis might contribute to an increased risk for atherosclerosis in individuals with essential hypertension.

Reticulate keloidal purpura associated with transient antiphospholipid antibodies and hyperhomocysteinaemia

A 66-year-old woman presented with a reticulate pattern of purpuric, keloidal scarring affecting her lower legs and necrosis of her left thumb and little finger as sequelae of an episode of staphylococcal septicaemia. Her premorbid past history includes three miscarriages, three episodes of pulmonary embolism and an internal iliac vein thrombosis. Skin biopsy specimens showed keloidal scar tissue in the dermis but no evidence of thrombosis or vasculitis. Blood tests demonstrated moderate hyperhomocysteinaemia. Elevated levels of anticardiolipin antibodies were found on one occasion but this was not detected on initial or repeat testing.

Placental Thrombosis in Experimental Anticardiolipin Antibodies‐Mediated Intrauterine Fetal Death

Anticardiolipin (aCL) antibodies are associated with stillbirths, recurrent miscarriages and recurrent in vitro fertilization implantation failure in women. Previous animal studies have demonstrated that these antibodies can cause early fetal demise and implantation failure in mice, but most previous studies have not allowed the immunized mice to proceed to the full term of gestation. Mice were immunized with either cardiolipin alone or cardiolipin in combination with beta2-glycoprotein I (beta2GPI) and have studied the effects of these antibodies on pregnancies which were allowed to progress to term. Immunization with cardiolipin alone induced significant levels of anticardiolipin antibodies in mice, but immunization with a combination of cardiolipin and beta2GPI produced even higher levels of antibodies. Mice with elevated levels of anticardiolipin antibodies had poor pregnancy outcomes. This study confirms previous results that anticardiolipin antibodies cause early pregnancy losses and also demonstrates that these antibodies cause stillbirth-like late fetal demise. This study further demonstrated that very high levels of anticardiolipin antibodies cause intrauterine death by facilitating the thrombotic episode in placenta. The present study concludes that the possible mechanism involves in stillbirth of aCL is possibly because of the thrombotic events of placenta.

A prospective study of anticardiolipin antibodies as a risk factor for venous thrombosis in a general population (the HUNT study).

We prospectively examined whether there is an association between elevated anticardiolipin antibody levels and the risk for a future first venous thrombosis (VT) in a general population. We studied this in a large population-based nested case-cohort study of 508 VT cases and 1464 matched control subjects from a cohort of 66,140 participants in the Health Study of Nord-Trøndelag in Norway. Venous thrombosis was validated using standardized criteria for venous thrombosis and pulmonary embolism. Prethrombotic serum anticardiolipin antibodies were measured by an enzyme-linked immunoassay. There was no association between elevated anticardiolipin antibody levels and subsequent venous thrombosis, overall or after stratification by sex, different age groups or idiopathic vs. secondary thrombosis. The overall odds ratio was 1.11 (95% CI: 0.71-1.74) for greater than vs. less than the 95th percentile of anticardiolipin antibody levels. In conclusion, in this general population sample elevated anticardiolipin antibody levels was not a risk factor for subsequent venous thrombosis.

Chagas disease and anticardiolipin antibodies in older adults

Infectious agents have been implicated in the induction of antiphospholipid antibodies and the development of antiphospholipid antibody syndrome. The objective of this study was to evaluate the association of anticardiolipin antibodies with Chagas’ disease antibodies. A total of 45 patients, who were positive for Chagas’ disease (American Trypanosomiasis) antibodies and had elevated levels of anticardiolipin antibodies, were investigated in a case–control study. Twenty-four of the patients were male and 21 female with ages ranging from 60 to 81 years and with a mean age of 68.3 years. Twenty-three female and 11 male individuals from a senior citizen support group who were apparently healthy formed a control group. Their ages varied from 62 to 80 years with a mean of 68 years. The measurement of anticardiolipin antibodies was performed by means of enzyme-linked immunoabsorbent assay (ELISA) for quantitative measurement of IgG and IgM antibodies against cardiolipins in serum and evaluation of Chagas’ disease was confirmed by the Machado Guerreiro test. Statistical analysis was made using Fisher's exact test with a confidence interval of 95% and a p-value <0.05. Elevated levels of anticardiolipin antibodies were detected in 48.8% of the patients and in 26.4% of the control group giving a p-value <0.038 using the Fisher's exact test. Thus, an association between Chagas’ disease antibodies and anticardiolipin antibodies was evidenced in this series of patients.

Adamantiades–Behçet's disease, deep venous thrombosis and anticardiolipin antibodies: report of two cases

Vascular thrombosis was found in different proportions of patients with Adamantiades-Behçet's disease (ABD), depending on the ethnicity of the population under study. Various thrombophilic factors, including the levels of anticardiolipin antibodies (ACA), were investigated for their role in the thrombotic process with conflicting results. The prevalence of ACA varies considerably in different studies, but their presence has not been associated with increased risk for vascular thrombosis. We present two cases with ABD, deep venous thrombosis (DVT) and elevated levels of ACA that fulfil the criteria for both ABD and antiphospholipid syndrome (APS).

Anti-cardiolipin antibodies in patients with inflammatory bowel disease.

Elevated levels of anti-cardiolipin antibodies are associated with an increased risk for venous and arterial thrombosis. In patients with inflammatory bowel disease thrombosis is a well known complication. We determined the prevalence of elevated anti-cardiolipin antibodies in 136 patients with inflammatory bowel disease compared with 136 healthy controls and analyzed thromboembolic complications in patients with increased anti-cardiolipin antibody levels. Anti-cardiolipin antibody titers were significantly elevated in patients with Crohn's disease (5.7 units/ml) and ulcerative colitis (5.3 units/ml) compared to the control group (2.5 units/ml). We found no correlation between disease activity and anti-cardiolipin antibody levels. Seven patients had deep venous thrombosis in their history, in three of them this was complicated by pulmonary embolism. In only two of the seven patients with deep venous thrombosis were anti-cardiolipin antibody levels increased. In conclusion, anti-cardiolipin antibody titers were significantly increased in patients with inflammatory bowel disease. Elevated anti-cardiolipin antibody levels appear to play no role in the pathogenesis of thromboembolic events in patients with inflammatory bowel disease.

Elevated levels of anticardiolipin antibodies and epilepsy in lupus patients.

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we investigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies (P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.

Anticardiolipin antibodies in systemic lupus erythematosus: Clinical and laboratory correlations

To examine the link between anticardiolipin antibodies and the features of antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE). In this prospective cohort study conducted in a single center, 390 SLE patients were followed up between June 1991 and 1994. At each assessment, a complete history, physical examination, and laboratory evaluation (including measurement of anticardiolipin antibodies) were performed according to a standard protocol. Forty-seven percent of the patients had an elevated level of anticardiolipin antibodies. In the univariate analysis, elevated anticardiolipin antibody levels were found to correlate with thrombocytopenia (P = 0.006), prolonged activated partial thromboplastin time (aPTT) (P = 0.003), and positive direct and indirect Coombs' test result's (P < 0.001). No correlation was identified with any of the clinical features of antiphospholipid syndrome. In the multivariate analysis, anticardiolipin antibodies remained highly associated with thrombocytopenia (odds ratio [OR] 4.05, P = 0.02), positive direct Coombs' test (OR 2.31, P < 0.001), and prolonged aPTT (OR 1.73, P = 0.03). In the multivariate model using venous/arterial thrombosis as the outcome variable, only prolonged aPTT was associated with venous/arterial thrombosis (OR 7.9, P < 0.001). None of the laboratory variables were found to correlate with fetal loss. The presence of anticardiolipin antibodies in patients with SLE is associated with prolonged aPTT, thrombocytopenia, and positive Coombs' test result, but not with antiphospholipid syndrome. Prolonged aPTT is strongly associated with venous/arterial thrombosis.

Fetal Outcome in Women With Primary Sjogren's Syndrome

OBJECTIVE To study fetal outcome in women with primary Sjogren's syndrome (SS) compared to that in women with systemic lupus erythematosus (SLE) and healthy women, and to study the possible association of fetal loss with anticardiolipin antibodies (aCL) and antibodies to SS-A/Ro and SS-B/La in women with primary SS. METHODS A retrospective analysis of the fetal outcome in 55 pregnancies in 21 patients with primary SS compared to that in 100 pregnancies in 42 patients with SLE and 94 pregnancies in 42 healthy women matched for age, parity and the onset of the autoimmune disease with respect to pregnancy. IgG-, IgM- and IgA-aCL were determined by a cofactor-dependent ELISA and antibodies to SS-A/Ro and SS-B/La by ELISA using human recombinant antigens and affinity-purified antigens. RESULTS Of all the 55 pregnancies in patients with primary SS, 8 (15%) occurred after the onset of primary SS symptoms. Eleven (20%) of the 55 pregnancies ended in fetal loss. The relative risk (RR) for fetal loss in patients with primary SS was 2.7 (95% CI 1.1-6.5; p = 0.023), and after the exclusion of the patient with four spontaneous abortions it was 2.0 (0.7-5.3; p = 0.18). In SLE the level of risk was 2.2 (0.9-5.0; p = 0.065). Fetal loss in patients with primary SS was not associated with elevated levels of anticardiolipin antibodies (aCL) or autoantibodies to SS-A/Ro or SS-B/La. Newborns of mothers with primary SS were not more premature or growth retarded than newborns of healthy women, but the absolute and the relative birth weights of the newborns of mothers with SLE was significantly lower than in healthy controls (P < 0.001 and P < 0.0001, respectively). CONCLUSION We conclude that the majority of pregnancies in women with primary SS occur before the onset of the disease and that these women have an increased risk of fetal loss, which is not associated with elevated levels of ACL or antibodies to SS-A/Ro or SS-B/La. The risk of fetal loss in primary SS is similar to that in women with SLE, but fetal growth retardation appears to be more common in SLE than in primary SS.

Hemiballismus in systemic lupus erythematosus: possible association with antiphospholipid antibodies

The neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are diverse but, among them, movement disorders are distinctly uncommon. We describe a 30-year-old female with SLE who developed sudden onset of right-sided hemiballismus. Previous cerebral venous thrombosis and a poor obstetric history suggested the antiphospholipid syndrome but only minimally elevated levels of anticardiolipin antibodies were detected. The underlying pathology could not be established but was most likely to have been a microinfarct of the contralateral subthalamic nucleus. Our patient responded rapidly to haloperidol alone without the requirement for corticosteroids.

Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis.

To determine whether the presence of anticardiolipin antibodies is a risk factor for ischemic stroke and venous thrombosis in healthy adult men. A nested, case-control study in a prospective cohort. A nationwide study of physicians. The study sample was drawn from the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 male physicians. At entry, 68% of the participants submitted plasma samples that were subsequently frozen at -80 degrees C. During 60.2 months of follow-up, follow-up for nonfatal outcomes was 99.7% complete and ascertainment of fatal outcomes was 100% complete. We identified men with documented ischemic stroke, deep venous thrombosis of the leg, or pulmonary embolus and for whom a plasma sample was available. A control was matched by age, smoking history, and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep venous thrombosis or pulmonary embolus. Plasma samples were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay. The mean anticardiolipin antibody titers of the case patients in the two diagnostic groups (ischemic stroke; venous thrombosis or pulmonary embolus) were compared with those of the control groups, and relative risks were calculated for patients in increasing percentile categories of anticardiolipin antibodies by conditional logistic regression. The anticardiolipin antibody titers were higher in case patients with deep venous thrombosis and pulmonary embolus than in their matched controls (P = 0.01). Persons with anticardiolipin antibody titers above the 95th percentile had a relative risk for developing deep venous thrombosis or pulmonary embolus of 5.3 (95% CI, 1.55 to 18.3; P = 0.01). The anticardiolipin antibody titers in case patients with ischemic stroke and controls were not significantly different (P > 0.2), and no clear trend of higher risks among those with elevated levels of anticardiolipin antibodies was observed. An anticardiolipin antibody level above the 95th percentile is an important risk factor for deep venous thrombosis or pulmonary embolus but not for ischemic stroke in healthy adult men.

Antibodies to Cardiolipin in Stroke: Association with Mortality and Functional Recovery in Patients Without Systemic Lupus Erythematosus

Antibodies to cardiolipin were measured in 100 consecutive patients with first ever stroke, on admission and at three and six months after the acute event. One hundred healthy, age- and sex-matched, British elderly individuals were also screened for antibodies to cardiolipin as a control group. Elevated levels of anticardiolipin antibody (i.e. 5 SD above the laboratory control mean) were present in none of the control group, but in 21 per cent of the patients with stroke. Thirteen of these 21 patients (62 per cent) died within three months, compared to 17 (21.5 per cent) of the seventy-nine patients without elevated levels of anticardiolipin antibodies (p less than 0.001). Six of the eight survivors with persistently elevated anticardiolipin antibodies had significant residual disability following stroke (Barthel score 0-9) compared to 11 of the 62 without (p less than 0.001). Two patients with initially raised anticardiolipin antibodies who became independent at six months showed a progressive decline in the level of these antibodies to normal. The presence of high levels of anticardiolipin antibody did not correlate with other recognized prognostic indices of stroke, except for incontinence. No correlation was noted between levels of antibody to cardiolipin, antinuclear factor, antibody to double-stranded DNA and C-reactive protein, either in the stroke patients or in the elderly control population. Hypertension was significantly more common in the patients with high anticardiolipin antibodies than in the rest of the patients in the stroke population (p = 0.33). There was no correlation between levels of anticardiolipin antibody and age. Anticardiolipin antibody may be considered as an independent prognostic marker for both mortality and clinical outcome after acute stroke.