Anticardiolipin syndrome in childhood: a report of two cases

We describe two children with an otherwise unexplained deep vein thrombosis associated with high titer anticardiolipin antibodies (ACA) of the IgG class and circulating lupus anticoagulant (LAC). One of these patients had persistent proteinuria but neither had systemic lupus erythematosus. Our observation suggests that ACA and LAC assays should be performed in children with thromboembolic disease even when no underlying autoimmune disease can be found.     

Lupus anticoagulants in systemic lupus erythematosus: prevalence and clinical associations.

The prevalence of lupus anticoagulant (LAC) and its relation with reported clinical associations has been determined in 55 patients with systemic lupus erythematosus (SLE) from northern India who were studied prospectively. Kaolin clotting time was used to screen for LAC, which was detected in seven (13%) of the patients. Significant associations were found between LAC and thrombotic events, onset of disease at an early age, and disease of shorter duration. No statistically significant association could be found between LAC and recurrent abortions, pulmonary hypertension, thrombocytopenia, and neurological manifestations. It is concluded that LAC is a useful marker for a subset of patients with SLE at risk of thromboembolic events.     

Catastrophic antiphospholipid syndrome in a patient with Behçet's disease

We report on a patient who had a life-threatening relapse of Beh?et's disease associated with a catastrophic antiphospholipid syndrome. The patient experienced over a short time a recurrent acute myocardial infarction, multiple venous thromboses, uveitis, and erythema nodosum. Search for thrombophilic factors was positive only for lupus anticoagulant (LAC) and criteria for the diagnosis of the antiphospholipid antibody syndrome were fulfilled. LAC was not found three months after the discharge. At that time the patient had no evidence of clinically active disease or thrombosis. We suggest that LAC was the main triggering factor for the repeated thromboses in this patient.     

Lupus anticoagulant,Factor V Leiden,and methylenetetrahydrofolate reductase gene mutation in a lupus patient with cerebral venous thrombosis

We describe the case of a young Lebanese woman with systemic lupus erythematosus (SLE) and a positive lupus anticoagulant (LAC) who developed right internal jugular vein and sigmoid sinus thrombosis. Coagulation studies showed that in addition to the LAC the patient was heterozygous for the factor V (FV) Leiden mutation, and C677T mutation of the methylenetetrahydrofolate reductase gene. The high prevalence of FV Leiden in the eastern Mediterranean region suggests that we should probably screen our SLE patients in this area, especially those with anticardiolipin antibodies and/or LAC who have no history of thrombosis, for this and other thrombophilia markers. The detection of such abnormalities may have major practical consequences for the long-term management of these patients to prevent further thrombotic episodes.Abbreviations APS Antiphospholipid syndrome - CVT Cerebral venous thrombosis - LAC Lupus anticoagulant - DVT Deep vein thrombosis - SLE Systemic lupus erythematosus - SVC Superior vena cava     

A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus

OBJECTIVE: To determine the prevalence of anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies, and lupus anticoagulant (LAC) in a large cohort of children with systemic lupus erythematosus (SLE), and to evaluate the associations with neuropsychiatric manifestations. METHODS: A single-center retrospective cohort study with longitudinal followup of antiphospholipid antibodies (aPL) in 137 children with SLE (25 boys and 112 girls, mean age at diagnosis 13.0 years) was performed. Patients were followed up for a mean of 31 months. RESULTS: At the time of diagnosis, 65% of the children were aCL positive, 41% had anti-beta(2)GPI antibodies, and 26% were LAC positive. Analysis of the association between presence of aPL and individual neuropsychiatric manifestations at diagnosis showed a statistically significant association of positive LAC with cerebrovascular disease (5 patients; P = 0.015). A persistently positive aCL was observed in 50%, anti-beta(2)GPI antibodies in 29%, and LAC in 16% of children over time. The prevalence of anti-beta(2)GPI antibodies, but not aCL and LAC, was found to be statistically significantly higher in children with neuropsychiatric disease compared with those without (P = 0.02). Comparison for specific neuropsychiatric manifestations showed a statistically significant association between a persistently positive LAC and chorea (2 patients; P = 0.02). CONCLUSION: The prevalence of anti-beta(2)GPI antibodies was found to be higher in the group of SLE patients with neuropsychiatric disease compared with those without. Our data suggest an association between LAC and cerebrovascular disease at the time of SLE diagnosis and chorea over the disease course, but not between aPL and other neuropsychiatric manifestations.     

Distribution and clinical significance of lupus anticoagulant and anticardiolipin antibody in 349 patients with systemic lupus erythematosus.

Samples from 349 patients with systemic lupus erythematosus (SLE) were tested simultaneously for lupus anticoagulant (LAC) and anticardiolipin antibodies (ACL). LAC was detected in 27.2% of 349 SLE patients by a modified mixing kaolin clotting time. ACL was detected in 34.7% by enzyme-linked immunosorbent assay. Only half of the patients who had LAC or ACL were positive for both of them. In addition, isotypes of ACL in these patients were studied. The IgG isotype was detected in 81.8% of 121 patients, and more than half had only the IgG isotype. When clinical features of patients with LAC or ACL were studied, the incidence of thrombosis, fetal loss, and thrombocytopenia were significantly higher in both groups compared with patients without LAC or ACL. In particular, the patients with both LAC and ACL showed the highest risk of fetal loss (89%) during pregnancy. These results indicate that LAC and ACL are detected in partly different groups of SLE patients, but both of these groups are clinically similar.     

The association between the lupus anticoagulant and cerebral infarction in systemic lupus erythematosus

The lupus anticoagulant (LAC) is associated with the occurrence of thromboembolic complications. Assuming that thrombosis may underlie manifestations of the central nervous system (CNS) in patients with systemic lupus erythematosus (SLE), we studied 20 patients with SLE and CNS manifestations for the presence of LAC. In 8 patients (40%) including 4 with overt cerebral infarction, LAC was demonstrated. The 4 patients with LAC and cerebral infarction all had thrombocytopenia, 2 had a history of peripheral thrombosis, and one recurrent abortion. In the 4 LAC-positive patients without overt cerebral infarction, thrombocytopenia was present in 3, a history of thrombosis in 2, and fetal wastage in one. We conclude that LAC identifies within the CNS-SLE group a subpopulation of patients in whom CNS manifestations are caused by cerebral infarction. This subpopulation is further characterized by increased prevalence of thrombocytopenia, peripheral thrombosis and fetal wastage. A possible pathogenetic role of LAC may be related to a hypercoagulable state occurring in this subgroup of SLE patients.     

The prevalence and clinical associations of the lupus anticoagulant in systemic lupus erythematosus

To determine the prevalence and clinical associations of the lupus anticoagulant (LAC) in patients with systemic lupus erythematosus (SLE), we studied 74 patients with SLE, 6 with lupus-like disease and a heterogeneous group of 45 patients with various autoimmune diseases. LAC was demonstrated in 19 SLE patients (26%), 5 patients with lupus-like disease (83%) and in none of the other patients. Statistically significant associations were found between LAC and a history of thromboembolic events (p less than 0.001), fetal loss (p less than 0.001), thrombocytopenia (p less than 0.01), biologically false-positive VDRL test (p less than 0.02) and convulsions (p less than 0.05). A negative correlation was found between LAC and a history of butterfly rash (p less than 0.01) and the presence of antibodies against extractable nuclear antigen (p less than 0.01). No significant difference was found between LAC-negative SLE patients and patients with other autoimmune diseases with respect to the prevalence of thromboembolic events or fetal loss. We conclude that LAC is a useful marker to identify a subset of patients with SLE or lupus-like disease at risk of thromboembolic events, fetal wastage, and thrombocytopenia.     

Primary antiphospholipid syndrome: a report of two pediatric cases

Two cases of primary antiphospholipid syndrome are described. A girl presented with myocardial infarction at the age of 6. afterward developed chorea, livedo reticularis, thrombocytopenia and circulating lupus anticoagulant (LAC). A boy, age 7, had an episode of intracranial hypertension and a deep venous thrombosis of a lower left limb, both recurrent in the following years. A high titer of IgG anticardiolipin antibodies (aCI) was detected. These observations suggest that both LAC and aCI tests should be performed in children with thromboembolic phenomena when the criteria for a definite autoimmune disease are lacking.     

Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions.

Brain magnetic resonance imaging (MRI) was performed in 21 patients with systemic lupus erythematosus (SLE) with and without lupus anticoagulant (LAC), one lupus-like patient and 5 patients with primary antiphospholipid antibody syndrome. Thirteen patients had white matter focal brain lesions on MRI, 10 of whom had LAC (p = 0.03). We found no correlation between these lesions and neurologic manifestations, nor any clinical or serologic indices of activity of SLE. Our MRI lesions were similar to those described in multiple sclerosis and may indicate a similar pathologic process.     

Multiple cerebral infarctions in a patient with refractory idiopathic thrombocytopenic purpura

Multiple cerebral infarctions were observed in a patient with refractory idiopathic thrombocytopenic purpura who was positive for lupus anticoagulant (LAC) when her platelet counts were 2000 μL⁻¹. It is suspected that LAC may have played an important role in the pathogenesis of this patient's cerebral infarctions, although she had severe thrombocytopenia.     

Intestinal pseudo-obstruction in patients with systemic lupus erythematosus: A real diagnostic challenge

Intestinal pseudo-obstruction secondary to systemic lupus erythematosus (SLE) is a rare syndrome described in recent decades. There are slightly over 30 published cases in the English language literature, primarily associated with renal and hematological disease activity. Its presentation and evolution are a diagnostic challenge for the clinician. We present four cases of intestinal pseudo-obstruction due to lupus in young Mexican females. One patient had a previous diagnosis of SLE and all presented with a urinary tract infection of varying degrees of severity during their evolution. We consider that recognition of the disease is of vital importance because it allows for establishing appropriate management, leading to a better prognosis and avoiding unnecessary surgery and complications.     

Prolonged bleeding time and lupus anticoagulant: a second paradox in the antiphospholipid syndrome

OBJECTIVE: Systemic lupus erythematosus and antiphospholipid syndrome (APS) often appear concomitantly. Lupus nephritis and antiphospholipid antibody-related ischemic nephropathy cannot be distinguished clinically, although their etiology and treatment differ greatly. Examination of a renal biopsy sample is therefore essential in order to provide the correct treatment. We have observed that patients with lupus anticoagulant (LAC), a serologic marker for APS, often have a prolonged bleeding time, which is a contraindication for performing a percutaneous renal biopsy. We undertook this study to evaluate systematically the bleeding time in 27 consecutive patients. METHODS: The bleeding time was measured in 27 patients who were persistently positive for LAC and who were not exposed to aspirin or nonsteroidal antiinflammatory drugs. Platelet function and von Willebrand factor (vWF) parameters were subsequently assessed in patients with a prolonged bleeding time. RESULTS: Twenty-one of 27 patients (78%) had a prolonged bleeding time despite a normal platelet count in the majority of patients (81%). Platelet functioning and vWF parameters in these 21 patients were normal, except for those in 1 patient with a mild storage pool disease. CONCLUSION: With this study, we introduce yet another paradox in the phenomenon of APS. Although a prolonged bleeding time is generally accepted to be a sign of defective primary hemostasis, LAC is associated with thrombosis. Further studies are needed to elucidate the mechanism behind this disturbance of primary hemostasis.     

Bilateral recurrent laryngeal nerve palsy in systemic lupus erythematosus

An unusual occurrence of bilateral recurrent laryngeal nerve palsy as an initial manifestation of systemic lupus erythematosus (SLE) is described. The patient had positive lupus anticoagulant (LAC) and high titers of anti-dsDNA antibody. She showed rapid improvement following intravenous pulse dexamethasone.     

Lower rates of oral transmission of La Crosse virus by Aedes triseriatus venereally exposed after engorgement on immune chipmunks

Transmission rates of La Crosse (LAC) virus observed in Aedes triseriatus females that had engorged on chipmunks with antibody to LAC and had been mated by infected males 5-11 days later (24%, 69/288) were 40% lower than in those fed on chipmunks without antibody (38%, 112/293). Similar results were obtained in three separate trials using males infected 1) by inoculation with prototype LAC virus, 2) transovarially with a field strain, or 3) transovarially with the field strain following passage through a viremic chipmunk. Similar rates were also observed in trials with F2 and F3 progeny of several strains of Ae. triseriatus collected from LAC-endemic and non-endemic areas. Reduction of oral transmission by venereally infected females mated by transovarially infected males following engorgement of antibody in chipmunks or other vertebrates could be important in the natural control of LAC virus, since most adult chipmunks sampled in endemic areas have antibodies neutralizing LAC. Ten-fold higher rates of venereal infection found in females mated by infected males 5 or more days after engorgement on LAC antibody-negative chipmunks than in those mated without prior engorgement extend previous findings of higher rates of transmission after engorgement on laboratory mice to include the natural vertebrate host.     

Beta2 glycoprotein 1 in Indian patients with SLE.

Forty-five patients with systemic lupus erythematosus (SLE) were investigated to evaluate the role of antiphospholipid antibodies in causation of thrombosis in Indians. The antiphospholipid antibodies studied included lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-beta(2)-glycoprotein 1 (a beta(2)-GP1). Twenty-seven patients (60%) had clinical manifestations of antiphospholipid antibody syndrome. Nineteen patients (42.2%) had a history of thrombosis, and eight (17.7%) had a history of recurrent fetal loss. aBeta(2)-GP1 was (IgG) was positive in 23 (51.1%), aCL in 13 (28.8%), and LAC in four (8.8%). Of 19 patients with thrombosis, 14 (73.6%) were positive for abeta(2)-GP1, eight (42.1%) for aCL, and none of them was positive for LAC. Of the eight patients with recurrent fetal loss, two (25%) patients were positive for beta(2)-GP1, five (62.5%) for aCL, and one (12.5%) for LAC. Of 18 patients without any manifestations of antiphospholipid syndrome (APS), seven patients (38.8%) were positive for abeta(2)-GP1, and three (16.6%) for aCL and LAC each. It is concluded that presence of abeta(2)-GP1 increases the risk of thrombosis and therefore should be looked for in all cases of SLE to consider prophylactic antithrombotic therapy in these patients.     

Anticardiolipin antibodies in patients with venous thrombosis

The levels of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) were measured in 266 consecutive unselected patients with a history of venous thrombosis. 19 (7.1%) had elevated levels of IgG- or IgM-ACA. The prevalence of LAC was 1 of 266 (0.4%) in the whole patient group and 1 of 19 (5.3%) in the ACA-positive group. Patients with elevated ACA levels did not differ from those with normal ACA with regard to age at the first thrombosis, risk of recurrence, presence of arterial thrombosis, and other clinical features. 8 out of 19 (42.1%) patients with elevated ACA levels also had elevated levels of antinuclear antibodies, but only 1 fulfilled the criteria of systemic lupus erythematosus. These data indicate that in some patients with elevated ACA, autoimmune processes may be present. The clinical significance of elevated ACA levels is uncertain.     

Significance of persistent antiphospholipid antibodies in the elderly

OBJECTIVE: The prevalence of anticardiolipin antibodies (aCL) and of vascular diseases increases with age, and aCL may be associated with various diseases in the elderly. So the significance of aCL in the elderly remains difficult to determine. We sought to determine the significance of persistent antiphospholipid antibodies (aPL) in the elderly. METHODS: We retrospectively analyzed the files of 327 patients [149 patients with antiphospholipid syndrome (APS); 64 patients age >or= 65 yrs] with 2 positive aPL [lupus anticoagulant (LAC) and/or aCL]. RESULTS: The frequency of APS was 40.8% (n = 134) in our 263 young patients (< 65 yrs) and 23.4% (n = 15) in our 64 elderly patients (>or= 65 yrs). The clinical characteristics of patients with persistent aPL were the same in those under and over 65 years. LAC was positive in all but one elderly patient with APS, and occurred in this group more frequently than in the young patients (93.3% vs 44.6%; p < 0.006). The presence of LAC allowed to discriminate APS patients in our elderly population (93.3% in APS vs 48.9% in non-APS patients; p < 0.009). CONCLUSION: Interpretation of a positive determination of APL is difficult in the elderly; persistent LAC may be the most valuable biological marker of APS in the elderly.     

Analysis of risk factors for the development of thrombotic complications in antiphospholipid antibody positive lupus patients

The objective of this study was to characterize risk factors for thrombotic events in lupus patients. A total of 272 lupus patients were followed up for five years during which the presence of aPL antibodies [anticardiolipin (aCL), anti-beta2-glycoprotein I (abeta2GPI) and lupus anticoagulant (LAC)] were determined, and all thrombotic incidents and antithrombotic therapy-related data were collected. At baseline, three groups were constituted, an aPL- group with 107 aPL negative patients, an aPL+ group with 81 aPL positive patients without clinical thrombosis and a secondary antiphospholipid syndrome (APS) group with 84 aPL+ patients who met the Sapporo criteria. LAC was more common in the APS than the aPL+ group (32.1% versus 9.9%, P < 0.001). The prevalence of clinical thrombotic events was significantly higher when all three types of aPL were present compared to only aCL positive cases. During follow up, aPL appeared in 7.5% of the aPL- group, and 2.8% of this group had thrombotic complications. In the aPL+ group, thrombotic events reoccurred in 1.9% of those receiving antithrombotic prophylaxis and 6.9% of those without primary prophylaxis. Despite anticoagulant therapy, thrombotic events reoccurred in 8.3% of the APS group. These findings indicate that LAC, constant and cumulative presence of aPL and previous thrombosis are positive predictors for the development of thrombotic complication in lupus patients.     

IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus erythematosus: prevalence and diagnostic value for the antiphospholipid syndrome

OBJECTIVE: To investigate the prevalence of serum anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies and other antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). To study their diagnostic value for the antiphospholipid syndrome (APS). METHODS: Anti-beta2-GPI and IgG anticardiolipin (aCL) were determined in sera from 102 consecutive patients with SLE using ELISA. Serum and plasma tests were also done for lupus anticoagulant (LAC), syphilis, and antibodies to dsDNA. Clinical and laboratory features of APS were observed. RESULTS: Prevalences were 23.5% for aCL and 18.6% for anti-beta2-GPI. Correlations between the presence of aCL and anti-beta2-GPI and between their titers were statistically significant (p<0.0001). No associations were found between anti-beta2-GPI and disease activity criteria (SLEDAI, ECLAM, dsDNA). Anti-beta2-GPI were significantly associated with LAC (p = 0.005), APS (p = 0.005), and a high aCL titer (aCL > 5 SD; p< or =0.001). LAC was the best diagnostic criterion for APS. CONCLUSION: These data suggest that determination of anti-beta2-GPI in addition to aCL and LAC is unlikely to improve the diagnosis of APS in patients with SLE.