IgM Anticardiolipin Antibodies Research Articles

Abstract TP419: PFO Stroke With Thrombophilia Has Higher Risk of Recurrent Stroke and Responds to PFO Closure

Background: Hypercoagulability due to thrombophilia may increase the risk of paradoxic embolism. However, previous randomized controlled trials that evaluated the efficacy of PFO closure or medical therapy on the risk of recurrent stroke and/or transient ischemic attack (TIA) events, have excluded these potentially high-risk thrombophilia patients. In this study, we want to investigate the effect of PFO management on the risks of recurrent stroke and/or TIA among patients with thrombophilia. Methods: Patients with a PFO attributable ischemic stroke or TIA are prospectively recruited. Hypercoagulable tests for protein C, protein S, antithrombin III, homocysteine levels, IgG and IgM anticardiolipin antibodies, factor V Leiden and prothrombin gene variant were obtained. The primary outcome was occurrence of stroke and/or TIA after index event. Results: Thrombophilia is diagnosed in 120 PFO stroke patients who subsequently underwent PFO closure (n= 76) vs medical therapy (n= 44) ( Table 1 ). The mean duration of follow-up was 45 months in the closure group and 40 months in the medical-therapy group. The primary end point occurred in 5 patients (6.6%) in the closure group and in 14 (31.8%) in the medical therapy group (hazard ratio for medical therapy vs. closure, 5.797; 95% confidence interval [CI], 2.094 to 16.051; P = 0.001) ( Figure 1 ) with recurrent rate of 18.2% vs. 5.3% for TIA (P = 0.023) and 13.6% vs. 1.3% for stroke (P = 0.018) respectively. Conclusions: PFO stroke patients with hypercoagulable state had higher rate of recurrent stroke than those patients in clinical trials. Among patients who had cryptogenic embolism with thrombophilia, closure of a PFO was associated with a lower rate of recurrent stroke and/or TIA than medical therapy.

Sekundarni fosfolipidni sindrom otkriven kod pacijenta sa pneumonijom - prikaz slučaja

Introduction: Secondary antiphospholipid syndrome (SAPS) is APS that occurs in the context of another medical condition. Although antiphospholipid antibodies (aPL) can occur in patients with viral, bacterial, or protozoal infections, they are rarely associated with thrombosis. Aim: To present an uncommon case of pneumonia and pleural effusion complicated with pulmonary thromboembolism in a patient with systemic lupus erythematosus (SLE), due to non-diagnosed secondary antiphospholipid syndrome. Case report: A 28 years old woman, never pregnant, with a family history of systemic lupus erythematosus, has been suffering from SLE from the age of 18. She had only articular and skin manifestations, without internal organ involvement. She has been taking Methotrexate (10 mg weekly) and Prednisone (5 mg daily) in the previous 10 years. She was presented at the Emergency department with the radiological finding of pleuropneumonia followed by temperature up to 39C, shortness of breath, cough, fatigue, and weakness. Results: She was treated initially with three antibiotics and thoracocentesis. She developed pulmonary thrombosis without deep venous thrombosis. Laboratory findings were: ESR = 37 mm/h, CRP = 2+, ANA = 1/80 peripheral, RF negative, anti-dsDNA = 147 (positive > 40), anti-Sm negative, anticardiolipin IgG antibody 158 GPL (up to 12), anticardiolipin IgM antibody 5.5 MPL (up to 10), anti-beta2-glycoprotein IgG and IgM were negative and lupus anti-coagulant was 88" (18"-55"). The patient underwent Heparin and Warfarin treatment, by checking INR to be in a 2.6 to 3.5 range. Prednisolone and Hydroxychloroquine were also started. Conclusion: All patients suspected with SLE should be evaluated for antiphospholipid antibodies (APL). However, APS diagnosis requires both clinical and laboratory features.

Stroke Associated With Recent Mycoplasma Pneumoniae Infection: A Systematic Review of Clinical Features and Presumed Pathophysiological Mechanisms.

Introduction: An association between Mycoplasma pneumoniae (MP) infection and stroke has been described, especially in children. However, current knowledge on this rare potential cause of stroke is scant. The purpose of this systematic review of all published cases was to help better understand the relationships between recent MP infection and ischemic stroke on a clinical, radiological and pathophysiological perspective.Material and Methods: A PubMed and Embase search was performed in September 2018 to identify all published cases of stroke occurring within 4 weeks after MP infection.Results: Twenty-eight patients with ischemic stroke associated with MP infection were identified. Median age was 8 years (range: neonate to 57). The middle cerebral artery territory was involved in 25 (89%) patients. Fifteen (54%) patients had at least one arterial occlusion. Elevated D-dimer and/or fibrinogen was reported in 8 (29%) patients. Four patients had transient anticardiolipin IgM antibodies. Cerebrospinal fluid analysis showed pleocytosis in 7/20 (35%) patients (median: 19 leucocytes/μL, range: 10 to 63) and MP PCR was positive in 3/8 (38%) patients. The etiological work-up was considered inconclusive in 25 (89%) patients. Three (11%) patients died during follow-up, all of early respiratory deterioration. Neurological functional outcome was good in 22/27 (81%) patients.Conclusion: The association between MP infection and ischemic stroke in children and young adults is rare. Underlying pathogenesis might include hypercoagulability and vasculitis. Most patients achieve a favorable recovery. Whether MP infection could be a long-term risk factor for stroke by promoting atherosclerosis is uncertain and deserves further investigation.

High incidence of co-existing factors significantly modifying the phenotype in patients with Fabry disease

Fabry disease results from deficiency of the lysosomal enzyme alpha-galactosidase A.The families of 11 index cases were screened by enzyme and molecular assays. Further clinical and laboratory investigations were carried out in all cases.Including 33 new patients, a total of 28 females (Age 25,82 ± 12,1 Range 8–46) and 16 males (Age 24,56 ± 15,04 Range 2–48) were investigated. Ten different disease-causing variants were found two of them being novel. One patient had co-existing familial mediteranian fever, one had celiac disease and three had rheumatological disorders. Lipoprotein (a) levels were elevated in 17,6%, homocysteine in 22,2%, total and low density cholesterol in 12% and antithrombin 3 levels were elevated in 13,3%. One patient was found to be heterozygous for prothrombin p.G20210A disease-causing variant (5,8%) and two for factor V Leiden disease-causing variant (11,7%). Anticardiolipin IgM antibody was found to be positive in 11,7%. The patients with abnormal cranial imaging were also noticed to have additional risk factors for thrombosis.This study provides the largest data about Fabry patients from Turkey and implies that co-existing risk factors unrelated to Fabry Disease have significant association with the presence of clinical symptoms in females and might cause an early and severe clinical course in males.

168. Comparison between frequency of thrombophilia in patients with and without severe preeclampsia in a Brazilian Tertiary Center.

Introduction In the last two decades studies have associated thrombophilia with the risk of developing severe preeclampsia (PE). Few of them, however, have been conducted in Latin America to assess the importance of thrombophilia in these patients. Objective Evaluate thrombophilia frequency among patients with and without severe preeclampsia in a Brazilian Tertiary Center. Methods From October 2009 to October 2015, a retrospective case-control study was conducted in pregnant women with severe PE and compared to normal pregnant women at Hospital das Clinicas, FMUSP. The patients with PE who had no gestational trophoblastic disease, foetal malformation or chromosomal abnormalities and who underwent thrombophilia screening during the postnatal period were included. Pregnant women without comorbidities and normal obstetric outcome were included to make up the normal group, and were screened for thrombophilia during prenatal care (when functional dosages were abnormal, they were repeated in the postnatal period). Factor V Leiden (FVL), G20210A prothrombin mutation (PM), antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The frequency of thrombophilia in the two groups was compared. Results We included 199 patients with severe pre-eclampsia and 50 normal pregnant women. In patients with severe PE we found 55 (27,6%) women that had at least one thrombophilia (14 Antiphospholipid Syndrome,10 heterozygous PM, 10 protein S deficiency, 9 hyperhomocysteinemia, 9 heterozygous FVL, 2 antithrombin deficiency, 4 association of thrombophilia). In the control group 2 (4%) women had positive thrombophilia research (1 heterozygous PM and 1 heterozygous FVL), p Discussion Our results show a higher rate of thrombophilia among the patients with servere PE (p

Association of anticardiolipin IgM antibody with preeclampsia

The objective of this study was to evaluate association of anticardiolipin IgM antibody with preeclampsia among the 70 pregnant women having preeclampsia from March 2016 to February 2017. Equal number of age matched normotensive healthy pregnant women was selected as control. Demographic, obstetric and relevant laboratory data were collected and compared between the two groups. The level of anticardiolipin IgM antibody was significantly higher in preeclamptic women than in normal pregnant (mean 8.7 vs 5.8 U/mL, p<0.001). Even in categorical distribution when the value was considered as positive by assessing a cut-off, cases had three times more chance to have positive level of anticardiolipin IgM antibody than controls (OR=3.3, 95% CI=1.1-9.6, p=0.046). Pearson’s correlation test revealed that both systolic and diastolic blood pressure had a positive correlation with the level of anticardiolipin IgM antibody. (p<0.05). In conclusion, this study shows that anticardiolipin IgM antibody was associated with preeclampsia. The level of this anticardiolipin IgM antibody is directly proportional to the severity of preeclampsia and both systolic and diastolic blood pressure.

Cryptogenic stroke as initial manifestation of CNS vasculitis: demonstration of vessel wall enhancement on 1.5T MRI using volumetric T1 TSE sequence

Central nervous system (CNS) vasculitis secondary to lupus anticoagulant is a rare but potentially lethal condition.1 We present a case report of a patient who presented with stroke and subsequently...

Efficiency of IgM Anti-Cardiolipin Serum Level Screening for Monitoring Response to Anti-Tuberculosis Treatment in Comparison with Sputum Smear Conversion Test

Background: Two original methods for evaluation of response to tuberculosis treatment are sputum smear and culture. Sputum smear test has a low sensitivity and sputum culture is not available in many countries with endemic tuberculosis. There are some biomarkers diseases such as IgM anti-cardiolipin antibody which could be assessed for this purpose. Objectives: Therefore, we decided to measure the reduction rate of IgM anti-cardiolipin antibody during treatment of smear positive pulmonary tuberculosis (PTB) patients for monitoring response to treatment and then compare efficiency of this test with sputum smear conversion. Methods: In this research study 30 sputum smear positive PTB patients were included by convenient sampling method and then their serum samples were taken before and after the first 3 months of anti-TB treatment for measurement of IgM anti-cardiolipin antibody serum level by Elisa method. Their serum level changes during treatment were analyzed by paired t test with SPSS software (ver.18). Results: The mean IgM anti-cardiolipin serum level during treatment showed significant reduction relative to its level at baseline in 27 (90%) of total patients (P < 0.0001). Also, this result was confirmed in both cavitary (P < 0.0001) and non-cavitary (P = 0.005) groups. The sensitivity of test (90%) was equal with sputum smear conversion rate in our study (90%) and was associated with clinical improvement in all of 30 cases (100%). Conclusions: The reduction of IgM anti cardiolipin serum level during treatment, could be a reliable indicator of effective treatment and specially it may be applicable in PTB patients who have negative sputum smear test or cannot deliver sufficient sputum for evaluation of response to anti-TB treatment.

Hydralazine-associated vasculitis: Overlapping features of drug-induced lupus and vasculitis.

Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447.6 or ICD10 code: I77.6, I80, L95, M30, or M31) and positive ANCA lab results over the past 15 years were identified. Age, gender, comorbid conditions, medications taken over the prior 6 months, laboratory data, including electrolytes, urine studies and serologies, chest x-rays, CT scans, and pathologic biopsy records were abstracted from the electronic medical record. 323 cases of AAV were identified, of which 12 were exposed to hydralazine, all at the time of diagnosis. The average duration of hydralazine therapy was 22 months and mean cumulative dose was 146g. Patients were typically older (70.3 years old) with slight female preponderance (7 females). Eleven patients presented with dyspnea, fatigue, and unintentional weight loss. Five had polyarthralgias and 8 had lower extremity petechiae. All 12 patients were both ANA and ANCA positive. ANA titers ranged from 1:160 and 1:2560. Ten were of diffuse pattern while 2 were nucleolar. ANCA titers ranged from 1:320 to 1:2560. Eleven had a pANCA pattern while one had cANCA. All 12 patients were positive for histone and 11 were positive for myeloperoxidase antibodies. Eleven also had dsDNA antibodies, and 4 had anti-cardiolipin IgG or IgM antibodies. Nine patients were also hypocomplementemic (mean C3 level: 88.4mg/dL; mean C4 level: 16.5mg/dL). All patients had variable levels of proteinuria (1+ to 3+) and eleven had active urine sediment. Urine protein:creatinine ratios ranged from 0.2 to 1.7. Of the 6 patients who underwent kidney biopsy, all 6 showed pauci-immune crescentic glomerulonephritis. Seven patients had bilateral pulmonary interstitial infiltrates and four had pleural effusions on CT scan. Four had pericardial effusions as demonstrated by echocardiography. Hydralazine-associated vasculitis is a drug-associated autoimmune syndrome that presents with interstitial lung disease, hypocomplementemia, and pauci-immune glomerulonephritis. Patients have elements of both DIL and DIV, as manifested by high ANA and ANCA titers as well as the presence of histone and MPO antibodies. Further research is needed to understand the etiopathogenesis of this condition.

Can thrombophilia worsen maternal and perinatal outcomes in cases of severe preeclampsia?

To evaluate whether thrombophilia worsens maternal and foetal outcomes among patients with severe preeclampsia (PE). From October 2009 to October 2014, an observational retrospective cohort study was performed on pregnant women with severe PE diagnosed before 34 weeks of gestation and their newborns hospitalized at the Clinics Hospital, FMUSP. Patients who had no heart disease, nephropathies, pre-gestational diabetes, gestational trophoblastic disease, foetal malformation, or twin pregnancy and who underwent thrombophilia screening during the postnatal period were included. New pregnancies of the same patient; cases of foetal morphological, genetic, or chromosomal abnormalities after birth; and women who used heparin or acetylsalicylic acid during pregnancy were excluded. Factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The groups with and without thrombophilia were compared regarding their maternal clinical and laboratory parameters and perinatal outcomes. Of the 127 patients selected, 30 (23.6%) had thrombophilia (hereditary or acquired). We found more white patients in thrombophilia group (p = .036). Analysis of maternal parameters showed a tendency of thrombophilic women to have more thrombocytopenia (p = .056) and showed worsening of composite laboratory abnormalities (aspartate aminotransferase ≥ 70 mg/dL, alanine aminotransferase ≥ 70 mg/dL, platelets < 100,000/mm3, serum creatinine ≥ 1.1 mg/dL; p = .017). There were no differences in foetal perinatal outcomes. The presence of thrombophilia leads to worsening of maternal laboratory parameters among patients with severe forms of PE but without worsening perinatal outcomes.

Late Presentation of SLE and Secondary Anti-phospholipid Syndrome, Following Initial Evans Syndrome

Background: Evans syndrome associated with secondary anti-phospholipid syndrome has not been reported in case studies and we report a case of SLE and secondary anti-phospholipid syndrome diagnosed seven years after the initial diagnosis of Evans syndrome. Case presentation: A 21-years-old female was diagnosed with Evans syndrome since the age of 14 years, and was on treatment for seven years. At the onset of disease her immunological screening for ANA, Ds-DNA were negative. She was treated with immunosuppressants and steroids and the disease was complicated with Cryptococcal meningitis. Seven years later at the age of 21 years she started to have joint arthritis, and the ANA test converted to positive together with a positive Ds-DNA. Later on she had a single episode of unprovoked deep vein thrombosis in a leg (below knee), and became positive for lupus anticoagulant and IgM anticardiolipin antibodies. Her cardiac imaging (Echo-cardiogram) revealed that she had developed moderate pulmonary hypertension. She was treated with physiotherapy, Methotrexate, Hydroxychloroquine, Warfarin and Sildenafil with good control of the disease. Her lupus is in remission with treatment with no anaemia. Conclusion: Haematological manifestations of systemic lupus erythematosus could vary. Hence, Lupus should be kept in mind always during management of complicated hematological conditions as the patient might fulfill cumulative SLE classification criteria over time.

Subclinical myocardial dysfunction by tissue Doppler echocardiography in primary antiphospholipid syndrome: Preliminary results

Aim of the workTo preliminary evaluate the myocardiac function in asymptomatic primary antiphospholipid syndrome (PAPS) patients using conventional and tissue Doppler echocardiogram. Patients and methodsNine female PAPS patients asymptomatic for cardiac manifestations and 7 matched controls were enrolled. Myocardial function was determined by echocardiogram (conventional and tissue Doppler imaging ‘TDI’ techniques). ResultsThe median age of the patients was 43 (26–55years) and disease duration 10 (3–19)years. Traditional cardiovascular risk factors were similar in PAPS and controls. Venous and arterial events were present in 55.6%, 22.2% showed obstetric features, 33.3% had stroke, 44.4% deep venous thrombosis and 66.7% had livedo reticularis. All patients were under oral anticoagulants with international normalization ratio within therapeutic range (2–3). 88.9% were positive for IgG and/or IgM anticardiolipin antibodies and 66.7% were positive for lupus anticoagulant. Conventional echocardiographic data were not altered in all evaluated parameters comparing patients and controls. Regarding TDI, a lower S’ (systolic wave which is related to systolic function in the analysed segment) of lateral wall of left ventricle was observed in PAPS in comparison to controls [0.085 (0.007–0.12) vs. 0.12 (0.09–0.13), p=0.004] as well as A′ wave of the septum (related to late diastolic function in the analysed segment) [0.07 (0.06–0.08) vs. 0.09 (0.07–0.11), p=0.02]. ConclusionThe present study demonstrated subclinical myocardial dysfunction using TDI in asymptomatic PAPS patients. TDI is non-invasive and cost effective. Prospective studies including a large number of participants in order to confirm these preliminary data are needed.

Total IgM and Anti-Phosphatidylcholine IgM Antibody Secretion Continue After Clearance of Mycobacterium bovis Bacillus Calmette-Guerin Pleural Infection.

The cellular immune response to Mycobacterium tuberculosis infection has been well characterized, while the humoral antibody response remains underexplored. We aimed to examine the total and anti-phospholipid IgM levels in the pleural lavage from mice with Mycobacterium bovis BCG extrapulmonary infection. We found that the levels of total and anti-phosphatidylcholine IgM antibodies remained significantly higher in infected mice as compared to non-infected mice up to day 90 after BCG infection, while the anti-cardiolipin IgM antibody levels decreased with bacteria clearance. Our findings suggest that IgM antibodies are secreted and their composition vary during early and late immune response to BCG pleurisy.

Thrombophilia in 153 Patients With Premature Cardiovascular Disease ≤Age 45.

We assessed contributions of thrombophilia to premature cardiovascular disease (CVD) events (≤ age 45) in 153 patients. Test results of thrombophilia-hypofibrinolysis were obtained in 153 patients with CVD ≤ age 45, 110 healthy normal controls, and 110 patients who had venous thromboembolism (VTE) without CVD. Of the 153 patients with CVD, 121 (79%) had sustained myocardial infarction, 70 (46%) had coronary artery stenting, and 53 (35%) had coronary artery bypass grafts. The first CVD events occurred at ages >20 to 35 in 47 patients and at ages >35 to 45 in 106 patients. At study entry, median low-density lipoprotein cholesterol was 126 mg/dL, 56 (37%) smoked, 56 (37%) had hypertension, and 56 (37%) were diabetic. Cases differed from normal controls for high factor VIII (10 [22%] of 45 vs 7 of 103 [7%], P = .007), high homocysteine (32 [21%] of 151 vs 5 [5%] of 107, P = .0002), low free protein S (5 [11%] of 44 vs 2 [2%] of 96, P = .032), high anticardiolipin antibodies (ACLA) IgM (11 [9%] of 129 vs 2 [2%] of 109, P = .024), high lipoprotein (a) [Lp(a)] (46 [30%] of 151 vs 21 [19%] of 110, P = .038), and the lupus anticoagulant (4 [11%] of 37 vs 2 [2%] of 110, P = .035). There were no differences ( P > .05) between cases and VTE controls except free protein S and Lp(a). Free protein S was more often low in VTE controls (24 [28%] of 85 vs 5 [11%] of 44, P = .03) and Lp(a) was more often high in cases (46 [30%] of 151, VTE controls 12 [17%] of 71, P = .032). In 153 patients with premature CVD ≤ age 45, thrombophilia was pervasive (high factor VIII, homocysteine, ACLA IgM, low free protein S, high Lp(a), and lupus anticoagulant), evidencing thrombotic contribution to premature CVD. Moreover, thrombophilia in patients with premature CVD was comparable to VTE controls, emphasizing the pervasive nature of thrombophilia in premature CVD.

Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

BackgroundFamilial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON.Case presentationCase 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. CT scan revealed bilateral femoral head ON without collapse. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). Apixaban 5 mg twice daily was substituted for warfarin; and L-arginine 9 g/day was started to increase NO. On Apixaban for 8 months, he became asymptomatic. Case 2: A 32-year-old hypogonadal Caucasian male had 10 years of unexplained tooth loss, progressing to primary jaw ON with cavitation 8 months after starting TT gel 50 mg/day. Coagulation studies revealed FVL heterozygosity, PAI 4G/4G homozygosity, and the lupus anticoagulant. TT was discontinued. Jaw pain was sharply reduced within 2 months.ConclusionsIdiopathic ON, often caused by thrombophilia-hypofibrinolysis, is worsened by TT, and its progression may be slowed or stopped by discontinuation of TT and, thereafter, anticoagulation. Recognition of thrombophilia-hypofibrinolysis before joint collapse facilitates anticoagulation which may stop ON, preserving joints.

Clinical relevance of antiphospholipid antibodies in systemic sclerosis: A systematic review and meta-analysis.

To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in systemic sclerosis (SSc). A systematic search of EMBASE and PubMed databases from January 1983 to July 2016 was carried out according to PRISMA guidelines whereas Peto׳s odds ratio (OR) for rare events was used for the meta-analysis. The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) antibodies was higher in SSc than controls (12.8% vs 1.6% and 7.8% vs 0.6%; p < 0.0001 for both) as was that of IgG and IgM anti-beta-2-glycoprotein-I antibodies (aβ2GPI) (6.1% vs 0.58%, p < 0.0001; 3.5% vs 0.3%, p = 0.001). The pooled prevalence of pulmonary arterial hypertension (PAH) was more common in SSc positive than negative patients for aCL (IgG/IgM combined) (26.5% vs 10.9%, p < 0.0001) whereas the pooled prevalence of renal disease (RD) was more common in IgG aCL positive than negative patients (36.3% vs 10.9%, p = 0.02). The pooled prevalence of thrombosis was higher in IgG aCL, IgM aCL, and IgM aβ2GPI positive than negative SSc patients (12.6% vs 1.4%, p < 0.0001), (15.1% vs 2.7%, p = 0.002) and (15% vs 0.78%, p = 0.009), respectively. The pooled prevalence of digital infarction/ischemia (DI) was higher in IgG aCL and IgM positive than negative SSc (52.8% vs 39.8%, p = 0.002) and (68.1% vs 29%, p = 0.07). A strong relationship exists between aCL and aβ2GPI of IgG/IgM isotype and SSc; patients positive for these antibodies are more likely to suffer from PAH, RD, thrombosis, and DI. However, data expressed as frequency of aPL positive patients rather than average antibody titers preclude further insight into the relevance of these assumptions.

Familial primary antiphospholipid syndrome: A report of co-occurrence in three Malaysian family members.

Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.

Association of Lupus Anticoagulant With Long-Term Damage Accrual in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antiphospholipid antibodies (aPL) are frequently present in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients; however, the prognostic impact of aPL in such patients has not been elucidated. The objective of this study was to determine whether persistent aPL positivity in AAV patients was associated with increased long-term damage accrual. Clinical data were retrospectively collected on all AAV patients who attended the vasculitis clinic at our center over a 4-year period. Data collection included presence of lupus anticoagulant (LAC) and IgG and IgM anticardiolipin (aCL) antibody titers, along with concurrent diagnosis of antiphospholipid syndrome (APS). Accumulation of long-term damage was quantified using the Vasculitis Damage Index (VDI). Data from 116 AAV patients were analyzed. A total of 34% (n = 40) had persistently positive aCL or LAC or a concurrent diagnosis of APS and were classified as AAV/aPL. A total of 76 patients (66%) were classified as AAV alone. LAC was present in a statistically higher proportion of AAV/aPL patients than those in the AAV-alone group (P < 0.0001). Mean VDI score was significantly higher in the AAV/aPL group at mean ± SD 3.54 ± 1.36 as compared to 1.96 ± 1.42 in the AAV-alone group (P < 0.0001). Major vascular damage scores were significantly higher in the AAV/aPL group, with mean ± SD 0.32 ± 0.59 as compared to 0.07 ± 0.26 in the AAV-alone group (P < 0.007). Persistently positive occurrence of aPL, in particular LAC, is present in a significant proportion of AAV patients and is associated with a higher VDI score. Clinicians should consider screening AAV patients for aPL.

Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies.

We evaluated analytical and clinical performances of IgG and IgM anticardiolipin (aCL) antibodies and anti-β2-glycoprotein I (a-β2GpI) antibodies and upper limit reference ranges (99th percentiles) in comparison with manufacturer's cutoff values with different commercial methods. We assayed aCL and a-β2GpI in serum samples from 30 healthy individuals, 77 patients with antiphospholipid syndrome (APS) diagnosed according to the Sydney criteria, 51 patients with autoimmune diseases, eight patients with previous thrombotic events, six patients with other diseases, and 18 patients with infectious diseases, using ELISA Inova Diagnostics; EliA Phadia Laboratory Systems; CliA Zenit-RA; and CliA Bio-Flash. Anticardiolipin and a-β2GpI IgG and IgM immunoassays showed good analytic performances with both 99th percentile and manufacturer's cutoff reference values. Our results showed fair to moderate agreement among assays. In-house cutoff values gave significantly better performances only for a-β2GpI IgG with all the immunoassays analyzed with the exception of Inova CliA Bio-Flash where we obtained the same performances with in-house and manufacturer's cutoffs. By guidelines, all laboratories are strongly advised to validate/verify the manufacturer's cutoff values. We recommend establishing low-positive, medium-/high-positive, and high-positive CliA IgG aCL and a-β2GpI ranges in order to help clinicians in the diagnosis and treatment of APS.

Aneurysmal Subarachnoid and Spinal Hemorrhage Associated With Systemic Lupus Erythematosus

A 42-year-old woman with systemic lupus erythematosis (SLE), positive lupus anticoagulant, elevated titers of IgG and IgM anticardiolipin antibody and β2 glycoprotein antibodies, idiopathic thrombocytopenia, and hemolytic anemia presented with menorrhagia and anemia. She received both platelet and red cell transfusions and had an unrevealing endometrial biopsy. She was treated with intravenous immunoglobulin therapy for autoimmune-mediated thrombocytopenia and was taking hydroxychloroquine 200 mg twice daily that was a home medication. She was started on prednisone 60 mg daily. During her hospitalization, she developed a sudden, severe, sharp, and pounding occipital and nuchal headache with sharp shooting pains radiating down the back of the neck. She was alert and oriented with normal cranial nerve function, motor strength, and sensation. Her headache was unsuccessfully treated with fioricet and acetaminophen. The day after headache onset, a noncontrast head computed tomography revealed a subarachnoid hemorrhage (SAH) extending from the interpeduncular fossa caudally to the cervicomedullary junction (Figure 1). Computed tomographic angiogram of the head and neck revealed a focal left vertebral artery stenosis with poststenotic aneurysmal dilation of the intradural (V4) segment. There were additional multifocal areas of beading and long tapered vessel narrowing involving the M2 division of the left middle cerebral artery and anterior cerebral arteries and M3 division of the right middle cerebral artery (Figure 1). Magnetic resonance brain demonstrated multifocal but posteriorly predominant T2 hyperintense lesions that resembled posterior reversible leukoencephalopathy syndrome (Figure 2). Conventional angiogram confirmed the global small and medium vessel vasculopathy with a left V4 vertebral artery fusiform aneurysm measuring 10.6 mm×5.5 mm distal to the origin of the left posterior inferior cerebellar artery (Figure 2). Figure 1. Lupus-associated central nervous system vasculitis and subarachnoid hemorrhage (SAH). A , Computed tomographic (CT) head demonstrating perimedullary SAH (black arrow). B , CT angiogram demonstrating focal stenosis of the intracranial …