Prevalence of Antiphospholipid Antibodies in Syrian Patients with Thrombosis

Background: Antiphospholipid antibodies (aPL) are a heterogeneous family of anti-bodies associated with thrombosis and other complications. Objective: To study the prevalence of aPL in patients with thrombosis at Aleppo University Hospitals, Syria. Methods: One hundred and fifty-seven patients with venous and arterial thrombosis and 63 healthy controls were studied. Anticardiolipin antibodies (aCL) and Lupus antico-agulant (LA) were determined. Results: Thirty-four out of 157 (21.7%) patients with thrombosis had some type of aPL. aPL was also found in four healthy subjects (4/63=6.3%). Eighteen patients (11.5%) were positive for LA, 20 (12.7%) for aCL anti-bodies and 4 (2.6%) were positive for more than one aPL. Patients without risk factors for thrombosis and having positive aPL were 23/34 (67.7%). Fourteen out of 78 (17.9%) patients with arterial thrombosis, and 20/79 (25.3%) with venous thrombosis were positive for at least one aPL. Conclusion: Our study showed a significant preva-lence of aPL in patients with thrombosis. It seems that aPL is a risk factor for venous and arterial thrombosis, especially in patients with no conventional risk factors.     

Interpretation and recommended testing for antiphospholipid antibodies

The antiphospholipid syndrome (APS) is defined by the association of arterial and/or venous thrombosis and/or pregnancy complications with the presence of at least one of the main laboratory-detected antiphospholipid antibodies (aPL) (i.e., lupus anticoagulants [LA], IgG and/or IgM anticardiolipin antibodies [aCL], and IgG and/or IgM anti-β2-glycoprotein I antibodies [aβ2GPI]). During the last decade efforts have been made to improve the harmonization and reproducibility of laboratory detection of aPL and guidelines have been published. The prognostic significance of aPL is being clarified through the fine elucidation of their antigenic targets and pathogenic mechanisms. Several clinical studies have consistently reported that LA is a stronger risk factor for both arterial and venous thrombosis compared with aCL and aβ2GPI. In particular, LA activity dependent on the first domain of β2-glycoprotein I and triple aPL positivity are prognosticators of the thrombotic and obstetric risks. Hopefully, this increasing knowledge will help improve diagnostic and treatment strategies for APS.     

Thrombosis risk in systemic lupus erythematosus: the role of thrombophilic risk factors

OBJECTIVES: Thromboembolic episodes are frequent manifestations of systemic lupus erythematosus (SLE). Although the presence of anti-phospholipid antibodies (aPL) is known to contribute to thromboembolism (TE), the relative contribution of other TE risk factors is unknown. The aim of this study was to determine the prevalence of TE in a Caucasian SLE population, to identify the risk factors of highest importance, and to assess the clinical value of thrombophilia screening among SLE patients. METHODS: Samples from 105 patients were analysed with a screen including aPL, activated protein C resistance, factor V Leiden (FVL) and prothrombin G20210A mutations; protein C, protein S and antithrombin activity; factor VIII (FVIII) and von Willebrand factor (vWF), and homocysteine (Hcy) levels. RESULTS: The annual incidence of arterial and venous TE events in our SLE population was 5.4 and 12.4 per 1000, respectively. The highest risk of thrombosis was carried by the simultaneous presence of lupus anticoagulant (LA) and anti-cardiolipin (aCL) [relative risk (RR) = 4.03, 95% confidence interval (CI) 2.06-7.86] or anti-beta2-glycoprotein I antibodies (abeta2-GPI) (RR = 5.10, 95% CI 2.58-10.1). Positivity for the individual aPL tests all carried an elevated TE risk. The presence of other risk factors seemed to be of less importance. CONCLUSIONS: In SLE patients, the presence of aPL is a more significant risk factor for the development of thrombosis than the known inherited deficiencies. Based on these data, routine screening for additional hereditary risk factors seems to be unwarranted.     

Safety and efficacy of low molecular weight heparins in children: a systematic review of the literature and meta-analysis of single-arm studies

Within the last two decades low molecular weight heparins (LMWH) have gained increasing widespread use as anticoagulants in children. The use of LMWH has been implemented into clinical care even though there is a lack of firm evidence on the efficacy and safety of LMWH in this population due to the absence of sufficiently powered randomized controlled trials. In the absence of clinical trials, we performed a meta-analysis of available single-arm studies using LMWH in children. A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1980 to 2010 was conducted using keywords in combination both as MeSH terms and text words. Two authors independently screened citations and those meeting a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients, ethnicity, venous thromboembolic events type, and frequency of recurrence and major bleedings were abstracted. Pooled incidence rates (IR) including 95% confidence intervals (95% CIs) on efficacy and safety data of LMWH administration on primary prophylaxis, as well as on secondary prophylaxis in children following symptomatic thromboembolism (TE) were shown. We included 2251 pediatric patients derived from 35 single-arm studies from 12 study countries who were eligible for analysis in the present systematic review. Pooled incidence rates (95% CI) to develop first TE on primary prophylaxis, further TE event on LMWH secondary prophylaxis, or a major bleeding event on LMWH were 0.047 (0.023 to 0.091), 0.052 (0.037 to 0.073) for efficacy, and 0.054 (0.039 to 0.074) for safety (treatment data only), respectively. Efficacy and safety data are comparable with adult data. The present systematic review suggests that use of LMWH in children as primary prophylaxis and in treatment of symptomatic thrombosis is effective and safe. However, properly designed randomized controlled trials are needed.     

Autoantibodies against C-reactive protein: clinical associations in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To investigate the prevalence of anti-C-reactive protein (CRP) autoantibodies in patients with systemic lupus erythematosus (SLE) and non-SLE patients with persistent antiphospholipid antibodies (aPL) and their association with clinical manifestations. METHODS: Sera of 137 patients with SLE, 127 with persistent aPL and 30 with idiopathic venous thromboembolic disease, were assayed for the presence of anti-CRP reactivity by ELISA. Associations of anti-CRP reactivity with clinical features, with other autoantibodies, and with serum concentrations of C3 and CRP were assessed. RESULTS: Antibodies against CRP were seen in 51% (n = 137) of patients with SLE and in 54% (n = 127) of patients with aPL. SLE patients with anti-CRP antibodies showed increased frequencies of anti-dsDNA and aPL antibodies compared to those without anti-CRP (52% vs 26% and 68% vs 31%, respectively). Mean serum C3 levels were lower in the subgroup of patients with SLE positive for anti-CRP antibodies (79 +/- 25 vs 92 +/- 25 mg/dl; p = 0.004 ) and mean serum CRP levels were significantly higher (13 +/- 17 vs 5 +/- 8 mg/l; p = 0.01 ). The frequency of nephritis was higher in SLE patients with anti-CRP antibodies, than in those without (27% vs 13%; p = 0.058). In patients with clinical and serological evidence of antiphospholipid syndrome (APS) the frequency of anti-CRP antibodies was significantly higher than in asymptomatic aPL carriers, in both SLE patients [85% (23 of 27) vs 59% (19 of 32); p = 0.021] and non-SLE patients [76% (38 of 50) vs 19% (9 of 47); p < 0.001]. Among patients with APS with or without SLE, 26 had arterial events, 31 had venous events, 6 had combined arterial and venous events, and 14 had fetal loss. Mean titers of IgG anti-CRP (29 +/- 21, 30 +/- 19, 60 +/- 37, and 26 +/- 12 AU/ml) and frequencies of anti-CRP antibodies (88%, 71%, 50%, and 71%) in these subgroups of patients were comparable. CONCLUSION: We confirmed the high prevalence of anti-CRP autoantibodies both in patients with SLE and in non-SLE and aPL-positive patients. We observed that the presence of these antibodies was associated with lupus nephritis and with clinical features of the APS in patients with lupus and non-lupus patients.     

Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome

The antiphospholipid syndrome (APS) is recognized increasingly as the most common acquired hypercoagulation state of autoimmune etiology and may occur as an isolated clinical entity (primary APS) or in association with an underlying systemic disease, particularly systemic lupus erythematosus (SLE). The major differences between pediatric and adult APS include absence of common acquired risk factors for thrombosis, absence of pregnancy-related morbidity, increased incidence of infection-induced antibodies, differences in cut-off values for determination of aPL and specific factors regarding long-term therapy in children. APS in children has been largely reported in patients with arterial or venous thromboses and less frequently in association with neurological or hematological manifestations. The presence of aPL in pediatric SLE can modify the disease expression and may be an important predictor of the development of irreversible organ damage. Two recently established international registries of neonates and children with APS provide a good opportunity to conduct large, prospective studies on the clinical significance of aPL and long-term outcome of pediatric APS.     

Prevalence and isotype distribution of antiphospholipid antibodies in unselected Chilean patients with venous and arterial thrombosis

Antiphospholipid antibodies (aPL) are a heterogeneous family of antibodies associated with thrombotic events and other complications. The objective of this study was to investigate the prevalence of aPL in a group of Chilean patients with thrombosis. Two hundred and twenty-six patients with venous and arterial thrombosis and 95 healthy controls were studied. Anticardiolipin (aCL), anti-₂ glycoprotein I (anti-₂GPI), and antiprothrombin (aPT) antibodies were determined. Eighty-eight out of 226 (38.9%) patients with thrombosis had some type of aPL. Fifty-seven patients (25.2%) were positive for aCL, 31 (13.7%) for aPT, and 14 (6.2%) for anti-₂GPI antibodies. Twelve patients (5.3%) were positive for more than one aPL. IgG, IgM and IgA isotypes were observed in aCL, anti-₂GPI, and aPT antibodies. Twenty-six out of 92 (28.3%) patients with venous thrombosis and 31/134 (23.1%) patients with arterial thrombosis were positive for aCL antibodies. With regard to the control group (4/95=4.2%), the odd ratios (OR) were 5.2 (1.3–19.8; p0.01) and 5.7 (1.6–22.3; p0.01), respectively. Additionally, we observed statistically significant OR with aPT and anti-₂GPI antibodies; in the first, with venous and arterial thrombosis, and in the second, only with arterial thrombosis. Our results show a significant prevalence of aPL, predominantly aCL and aPT antibodies, in patients with thrombosis. Additionally, aCL and aPT antibodies appear to be a risk factor for venous and arterial thrombosis, and anti-₂GPI antibodies appear to be a risk factor for arterial thrombosis.Abbreviations aCL Anticardiolipin antibodies - aPL Antiphospholipid antibodies - AMI Acute myocardial infarction - BSA Bovine serum albumin - DVT Deep venous thrombosis - FBS Fetal bovine serum - IS Ischemic stroke - LA Lupus anticoagulant - RT Room temperature - RVT Retinal vein thrombosis - SLE Systemic lupus erythematosus     

Novel considerations in the pathogenesis of the antiphospholipid syndrome: involvement of the tissue factor pathway of blood coagulation

The antiphospholipid syndrome (APS) is characterized by clinical manifestations such as venous and arterial thrombosis, thrombocytopenia and/or recurrent pregnancy loss, as well as the persistent presence of laboratory markers of antiphospholipid (aPL) antibodies detected in laboratory assays. Though it is generally accepted that aPL antibodies, such as anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulants (LA) contribute to the pathogenesis of APS, precise mechanism(s) are yet to be fully described. It is probable that aPL antibodies bind to a range of cellular targets (e.g., platelets, endothelial cells, and monocytes), leading to thrombosis and obstetric complications. There is now increasing evidence that alterations to the tissue factor (TF) pathway of blood coagulation contribute toward hypercoagulability in patients with aPL antibodies. This article reviews current evidence that suggests changes and/or interference to the major pathway of blood coagulation may represent a novel mechanism that contributes to the development of APS.     

A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies

OBJECTIVE: To systematically review the efficacy and safety data of different therapeutic approaches in patients with antiphospholipid antibodies (aPL) and thrombosis. METHODS: The Medline database and references from selected reports and review articles were used. Randomized controlled trials, prospective and retrospective cohort studies, and subgroup analysis (n > 15) that focused on the secondary thromboprophylaxis in patients with aPL were selected. RESULTS: Sixteen studies were selected. Patients with venous events and a single test for aPL showed a low recurrence rate while receiving oral anticoagulation at a target international normalized ratio (INR) of 2.0-3.0. Patients with stroke and a single positive aPL test had no increased risk compared with those without aPL. Recurrence rates in patients with definite antiphospholipid syndrome (APS) and previous venous thromboembolism were lower than in patients with arterial and/or recurrent events, both with and without therapy. Only 3.8% of recurrent events occurred at an actual INR >3.0. Mortality due to recurrent thrombosis was higher than mortality due to bleeding (18 patients versus 1 patient reported). CONCLUSION: For patients with definite APS, we recommend prolonged warfarin therapy at a target INR of 2.0-3.0 in APS patients with first venous events and >3.0 for those with recurrent and/or arterial events. For patients with venous thromboembolism or stroke and a single positive aPL test, we recommend further testing to determine if they have a persisting antibody. If they do not, the same therapy as for the general population should be used (warfarin at a target INR of 2.0-3.0 and low-dose aspirin, respectively).     

Prevalence of antiphospholipid antibodies is not different in Chilean diabetic patients and normal individuals

Diabetes mellitus (DM) is complicated by vascular and neurological events. Antiphospholipid (aPL) antibodies have already been associated with many clinical conditions, including venous and arterial thrombosis, as well as recurrent fetal loss. However, a significant association between aPL antibodies and DM has not been widely reported yet. In the present study, we investigated the prevalence of aPL antibodies in diabetic patients. This study included 100 Chilean diabetic patients (67 of them with some complications and 33 without complications; 28 with Type 1 and 72 with Type 2 DM) and 100 healthy blood donor controls. Each sample was analyzed for IgG, IgM and IgA anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), antiprothrombin (aPT) antibodies, and lupus anticoagulant (LA). Fourteen out of 100 (14%) diabetic patients presented some type of aPL antibodies. Four patients were positive for aCL antibodies, two for anti-beta(2)GPI antibodies, and nine for aPT antibodies. All patients were LA negative. The incidence of different isotypes was similar in each of the aPL antibodies studied, and their activities were low. No significant correlation was observed between aPL antibodies and vascular complications.     

Thromboembolism in paediatric lupus patients

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants (LAC) are at high risk of developing thromboembolic events (TE). Our objectives were to determine the prevalence of TE in paediatric SLE patients with LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range 11.4-18.4). Long-term anticoagulation was prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombin III. One patient is heterozygous for Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeutic anticoagulation. Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.     

Antiphospholipid syndrome

Since 1987 the antiphospholipid syndrome has been recognized as a major cause of acquired thrombophilia, whether it is associated with systemic lupus erythematosus or occurs as a free-standing syndrome (primary form). This autoimmune condition associates in young patients recurrent thrombosis (both venous and/or arterial) and/or a variety of obstetric complications with the persistent presence of antiphospholipid antibodies (aPL). These traditionally comprise anticardiolipin antibodies and lupus anticoagulants, respectively detected by immunological and clotting tests. Despite their name aPL do not bind to phospholipids per se, but are directed at phospholipid-binding plasma proteins, especially beta 2-glycoprotein I and prothrombin. Because the risk of recurrence is high, the standard of care is prolonged and high-intensity warfarin (INR near 3) after a venous thromboembolic event, together with the management of associated vascular risk factors. Prevention of adverse obstetric outcomes is frequently achieved by a combination of low-dose aspirin and heparin.     

Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies

OBJECTIVE: Impaired fibrinolytical outcomes may be one of the pathogenic factors for thrombotic events in patients with antiphospholipid antibodies (aPL). We investigated the consequences of the gene polymorphisms of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients positive for aPL. METHODS: Seventy-seven Japanese and 82 British patients with aPL were examined for Alu-repeat insertion (I)/deletion (D) polymorphism of the tPA gene by polymerase chain reaction (PCR), and 4G/5G polymorphism in the PAI-1 promoter gene by site-directed mutagenesis-PCR and restriction fragment length polymorphism analysis. Correlations between these polymorphisms and clinical symptoms of antiphospholipid syndrome (APS) (arterial thrombosis, venous thrombosis, miscarriage) were analyzed. RESULTS: Significant differences in the allele frequencies of these genes did not exist between patients and controls. There was no significant correlation between these gene polymorphisms and clinical symptoms of APS in patients with aPL. CONCLUSION: Polymorphisms of the tPA or PAI-1 genes probably do not significantly influence the risk of anerial thrombosis, venous thrombosis, or pregnancy morbidity in patients with aPL.     

Factor V Leiden,prothrombin gene mutation,and thrombosis risk in patients with antiphospholipid antibodies

OBJECTIVE: To determine if the prevalence of 2 prothrombotic genetic factors, factor V Leiden and prothrombin gene mutation, is increased in patients with antiphospholipid (aPL) antibodies with a history of venous/arterial thrombosis compared to patients with aPL antibodies with no history of thrombosis. METHODS: One hundred fifty-seven patients with aPL antibodies were studied. The occurrence of venous and arterial thrombotic events since the time of antibody detection was determined retrospectively, using appropriate clinical and diagnostic criteria. Clinical risk factors for thrombosis were documented and included hypertension, hyperlipidemia, cigarette smoking, diabetes, positive family history, use of oral contraceptive, pregnancy, trauma, hospitalization, varicose veins, and malignancy. Genomic DNA was extracted from blood cells for determination of factor V Leiden mutation G1691 --> A and prothrombin mutation G20210 --> A by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Of 157 patients, 69 had a history of thrombosis (venous 37, arterial 32); 147 (94%) patients had anticardiolipin (aCL) antibodies; 69 (45%) had lupus anticoagulant (LAC). The prevalence of factor V Leiden in patients with thrombosis was 13% compared to 4.6% in patients without thrombosis (OR 3.11, CI 0.92-10.6). In patients with aCL antibodies, 15% of patients with arterial thrombosis had factor V mutation compared to 3.5% of patients without thrombosis (OR 4.9, CI 1.2-19.3). The prothrombin gene mutation was identified in 5 patients, none of whom had thrombosis. Stepwise logistic regression analysis indicated that LAC (p = 0.005), male sex (p = 0.04), and hypertension (p = 0.03) were the strongest risk factors for developing thrombosis and that no additional risk was conferred by factor V Leiden (p = 0.13) and prothrombin gene mutation. CONCLUSION: Although the prevalence of factor V Leiden is modestly increased in patients with autoimmune aPL antibodies and thrombosis, these results suggest that its detection does not significantly increase the risk of a thrombotic event, once other clinical risk factors have been considered. Prothrombin gene mutation is not associated with thrombosis in patients with aPL antibodies.     

Pathogenic role of antiphospholipid antibodies

The antiphospholipid antibody syndrome (APS) is characterized by recurrent arterial and venous thrombosis and/or pregnancy in association with antiphospholipid (aPL) antibodies. The pathogenic mechanisms in APS that lead to in vivo injury are incompletely understood. Recent evidence suggests that APL antibodies alter regulation of haemostasis and induce activation of complement. We will discuss the current knowledge on how aPL antibodies trigger increased inflammation and enhanced thrombotic tendency, and thereby lead to tissue damage.     

Oral contraception and the risk of hepatocellular carcinoma

BACKGROUNDS/AIMS: We performed a meta-analysis of observational epidemiological studies to examine the association between oral contraceptives (OC) and hepatocellular carcinoma (HCC). METHODS: Two independent researchers conducted PubMed searches followed by systematic abstraction of studies that compared OC use between patients with HCC and a group of controls. Pooling of ORs was conducted using a random effects model. Heterogeneity and publication bias among studies were examined. RESULTS: Twelve case-control studies that included 739 cases and 5223 controls met the inclusion and exclusion criteria. The pooled estimate of ORs (age- and sex-matched only) from all 12 studies was 1.57 (95% CI=0.96-2.54, p=0.07) with a heterogeneity of I(2)=39.9. Exclusion of one large multi-national European study decreased the heterogeneity to I(2)=16.9 and increased the pooled OR to 1.70 (95% CI=1.12-2.59, p=0.01). Eight studies reported adjusted ORs (in addition to age and sex); the pooled estimate was 1.45 (95% CI=0.93-2.27, p=0.11) with a heterogeneity of I(2)=20.4. Only few studies identified or adjusted for other HCC risk factors. Six studies showed a significant 2- to 20-fold increase in HCC risk with longer durations of OC use; however, the reporting was too inconsistent to allow meta-analysis. CONCLUSIONS: The evidence is inconclusive to establish a relation between oral contraceptives and the risk of hepatocellular carcinoma. Future studies should focus on the duration, intermittency, and recency of OC use.     

Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus

OBJECTIVE: Although antiphospholipid antibodies (aPL) are associated with arterial and venous thrombosis in systemic lupus erythematosus (SLE), the extent to which they influence other cardiovascular manifestations is either controversial or uncertain. We undertook this study to examine the relationships of aPL with valvular, myocardial, and arterial disease in SLE. METHODS: Two hundred patients in an SLE registry, recruited at the time of outpatient visits, underwent comprehensive interviews, physical examinations, laboratory assessments, echocardiography to assess left ventricular (LV) and valvular status, carotid ultrasonography to detect atherosclerosis (discrete plaque), and radial applanation tonometry to measure arterial stiffness. RESULTS: Antiphospholipid antibodies were present(defined as IgG or IgM anticardiolipin > or =40 IU/ml or the presence of lupus anticoagulant) in 42 patients (21%). Mitral valve nodules and moderate-to-severe mitral regurgitation were more common in aPL-positive patients (both 14.3% versus 4.4%; P = 0.02). Thirty-one percent of patients with high titers of IgG aPL (>80 IU/ml) had mitral valve nodules, compared with 20% of patients with mildly to moderately elevated levels of IgG aPL (16-80 IU/ml) and 4% of patients without IgG aPL (overall P < 0.001). Levels of soluble tumor necrosis factor receptors were higher in the presence of both aPL and mitral valve nodules. LV dimensions, systolic function, and carotid artery stiffness as well as prevalences of Raynaud's phenomenon, pulmonary hypertension, and atherosclerosis were similar in aPL-positive and aPL-negative patients. CONCLUSION: Antiphospholipid antibodies in SLE are associated with mitral valve nodules and significant mitral regurgitation, possibly due to valvular endothelial cell activation. However, in this population, they are not associated with evidence of myocardial hypertrophy, systolic dysfunction, coronary or carotid atherosclerosis, or other vascular abnormalities.     

Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: A meta-analysis of observational studies

ObjectivePatients with inflammatory bowel disease (IBD) are at increased risk of having venous thromboembolism. The magnitude of this risk has yet to be determined. The question of whether IBD patients have an increased risk of arterial thromboembolism and cardiovascular (CV) mortality remains controversial.DesignWe searched MEDLINE, Cochrane Library, EMBASE and international conference abstracts and included all controlled observational studies that evaluated the incidence of venous and/or arterial thromboembolic events (TE) and CV mortality in adult IBD.Results33 studies enrolling 207,814 IBD patients and 5,774,898 controls and capturing 3,253,639 hospitalizations of IBD patients and 936,411,223 hospitalizations of controls reported a risk of arterial and/or venous TE or CV mortality were included. The risk of venous TE was increased in IBD patients compared to the general population (RR, 1.96; 95% CI, 1.67–2.30) contrary to the risk of arterial TE (RR, 1.15; 95% CI, 0.91–1.45). There was an increased risk of deep venous thrombosis (RR, 2.42; 95% CI, 1.78–3.30), pulmonary embolism (RR, 2.53; 95% CI, 1.95–3.28), ischemic heart disease (RR, 1.35; 95% CI, 1.19–1.52) and mesenteric ischemia (RR, 3.46; 95% CI, 1.78–6.71). Differences in methodology were great between studies resulting in a significant heterogeneity in all previous analysis. CV mortality in IBD patients was not increased compared to the general population (SMR, 1.03; 95% CI, 0.93–1.14).ConclusionThe risk of TE is increased in patients with IBD. This difference is mainly due to an increased risk of venous TE. There is no increased risk of arterial TE or CV mortality in IBD patients, but an increased risk of both ischemic heart disease and mesenteric ischemia.     

Bleeding in the antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized clinically by the occurrence of venous or arterial thrombosis, and/or pregnancy morbidity. The detection of persistently elevated levels of antiphospholipid antibodies (aPL) is a requisite laboratory feature for the diagnosis of APS. The positivity for at least one aPL test: lupus anticoagulant and/or IgG/IgM anticardiolipin and/ or IgG/IgM anti-β2 glycoprotein I antibodies must be detected. Sometimes aPL coagulopathy may start with a hemorrhagic syndrome when a severe thrombocytopenia, or an acquired thrombocytopathy, or an acquired factor VIII inhibitor, or an acquired prothrombin deficiency is present. aPL-associated thrombocytopenia is usually moderate without clinical manifestations. Except in the occasional situations in which thrombocytopenia is associated with thrombotic microangiopathy, such as catastrophic APS, bleeding is uncommon in APS patients. When platelet counts are less than 30 × 109/L and there are symptoms of bleeding, the treatments used are the same for idiopathic thrombocytopenic purpura. In rare occasions a hemorrhagic diathesis due to the occurrence of non-neutralizing anti-prothrombin antibodies causing severe hypoprothrombinemia (HPT) can be observed. Levels of prothrombin in plasma are less than 10-20% in cases with HPT-related bleeding requiring transfusion and/or corticosteroid treatment. The APS mainly causes thrombosis, and pregnancy losses. However, other clinical manifestations are also associated with the presence of persistent autoimmune aPL. Bleeding is uncommon but can be the first clinical manifestation in patients having severe thrombocytopenia or prothrombin deficiency.     

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events

OBJECTIVE: To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). Methods: Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. RESULTS: A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. CONCLUSIONS: Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive treatment strategies should be directed to both smoking cessation and control of disease activity in patients with SLE.