Risk of death, thrombotic and hemorrhagic events in anticoagulated patients with atrial fibrillation and systemic autoimmune diseases: an analysis from a global federated dataset.

BACKGROUND: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. METHODS: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI). RESULTS: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09-1.71), thrombotic events (HR 1.37, 95%CI 1.32-1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33-1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE. CONCLUSION: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis.

Acquired factor V and factor X Deficiency coexisting with acquired dysfibrinogenaemia in a patient with light chain myeloma.

An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia.

Relevance of vein wall thickness in Behcet's disease: A systematic review and meta-analysis.

OBJECTIVES: To perform a meta-analysis on articles evaluating the common femoral vein wall thickness (VWT) in Behcet's disease and its possible clinical, laboratory and treatment correlates (BD). METHODS: Systematic search of EMBASE and PubMed databases from inception to October 2023; we employed random effect meta-analyses for continuous outcomes. RESULTS: The meta-analysis included 9 case-control and 1 cohort study: the VWT was greater in BD (n = 650) than in controls (n = 396) (p < 0.0001) with wide heterogeneity (I2 = 94.4%); a sensitivity analysis that included mean age of BD participants, gender, disease duration and activity, C-reactive protein, smoking status, immune-suppressive and anti-inflammatory medication, revealed that the heterogeneity variance was partly explained by age (p < 0.0001), male gender (p = 0.03), disease duration (p < 0.0001) and smoking (p = 0.06). The VWT was greater in BD with thrombotic/vascular (n = 189) than in non-thrombotic/vascular BD (n = 140) (p = 0.006) with no heterogeneity. CONCLUSION: VWT is greater in BD than controls: age, male gender, disease duration and smoking relate to VWT that was greater in BD patients with a history of thrombotic/vascular disease. Prospective studies are required to assess whether VWT may be considered a vascular marker of disease activity.

Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study.

INTRODUCTION: Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as "second hit" in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. PURPOSE: To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. METHODS: Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. RESULTS: In the whole cohort (median age 51 years (IQR 43-60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: -0.295, p = 0.001) and NO (rS: -0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. CONCLUSION: Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts.

Subclinical atherosclerosis in Behcet's disease and its inverse relation to azathioprine use: an updated meta-analysis.

To evaluate the intima media thickness of carotid arteries (IMT) and its clinical, laboratory and treatment correlates in Behcet's disease (BD). Systematic search of EMBASE and PubMed databases from January 2016 to October 2022; we employed random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events. The meta-analysis included 36 case control studies: the IMT was greater in BD (n = 1103) than in controls (n = 832) (p < 0.0001) with wide heterogeneity (I2 = 86.9%); a sensitivity analysis that included mean age of BD participants, gender, disease duration and activity, atherogenic index of plasma, blood pressure, C-reactive protein, ethnicity, smoking status, anti-inflammatory and immune suppressive agents, revealed that male gender, mean age of participants and azathioprine use (the latter two in inverse fashion) partly explained the heterogeneity variance (p = 0.02, p = 0.005, and p = 0.01). The IMT was greater in vascular (n = 114) than in non-vascular BD (n = 214) (p = 0.006). BD patients (n = 782) had a greater pooled prevalence of carotid plaques than controls (n = 537) (13.1% vs. 2.97%, p < 0.0001). Subclinical carotid artery atherosclerosis represents a vascular feature of BD, independently of the traditional cardiovascular risk factors. The inverse correlations between IMT, age and azathioprine use suggest that thicker carotid arteries at disease onset eventually regress with immune suppressive treatment: this assumption needs verification on adequately designed clinical trials.

Efficacy of extended microthrombolysis in an elderly lady with purpura fulminans.

Purpura fulminans is a thrombotic emergency affecting small vessels of skin and of internal organs that may rapidly progress into necrotizing fasciitis, critical limb ischaemia and multiorgan failure; it often develops during an infection or as a postinfective 'autoimmune' disorder. Although supportive care and hydration are important, anticoagulation ought to be started to prevent further occlusions alongside blood products according to need. Herein, we describe the case of an elderly woman who received extended intravenous low-dose recombinant tissue plasminogen activator at the onset of purpura fulminans that salvaged her skin and prevented the development of multiorgan failure.

Earlier onset of peripheral arterial thrombosis in homozygous MTHFR C677T carriers than in other MTHFR genotypes: a cohort study.

To investigate whether age at first presentation of pure peripheral arterial thrombosis (PAT) in lower and upper limbs and in the splanchnic circulation occurs earlier in carriers of the methylenetetrahydrofolate reductase (MTHFR) T677T genotype compared to the heterozygous and wild type and to identify predictors of a possible earlier onset. Retrospective cohort study on 27 MTHFR TT, 29 MTHFR TC and 29 MTHFR CC participants; data regarding age, sex, age at PAT, clinical history (dyslipidaemia, hypertension, smoking, obesity) and homocysteine (HC) measured by immunoassay were collected. Age at PAT was lower in MTHFR TT than MTHFR TC and CC (43 ± 9 vs 47 ± 9 vs 51 ± 4 years, respectively, p = 0.02); plasma HC was higher in MTHFR TT than in the other groups (25 ± 19 vs 12.7 ± 6.7 vs 11.3 ± 3.3 µmol/l, respectively, p < 0.001) while the activated partial thromboplastin ratio (aPTTr) was lower in MTHFR TT than in other genotypes (0.90 ± 0.10 vs 0.97 ± 0.12 vs 0.97 ± 0.08 µmol/L p < 0.001). Among categorical variables, MTHFR TT and dyslipidaemia independently predicted age at AT (p = 0.01 & p = 0.03, respectively) whereas among the continuous variables HC independently predicted age at PAT (p = 0.02) as well as the aPTTr (p = 0.001); smoking predicted lower limb PAT (p = 0.005). MTHFR TT carriers develop their first PAT an average of 4 and 8 years earlier than MTHF CT and CC genotypes; MTHFR TT, dyslipidaemia and plasma HC contribute to the prematurity of the PAT while the interplay between elevated HC and smoking may affect type of arterial district occlusion.

Liver Cirrhosis Patients Homozygous for MTHFR C677T Develop Portal Vein Thrombosis 8 Years Earlier Than Wild Type.

BACKGROUND AND AIM: Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C → T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT. APPROACH AND RESULTS: Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G → A 20,210 transition), plasma HC and natural anticoagulants available for all participants. Age at PVT was lower in MTHFR TT than CT and CC (56 ± 13 vs. 57 ± 13 vs. 64 ± 9 years, p = 0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [(17 (9.4, 23.3) vs 13 (8,14.7) vs 11 (8.9, 12.7) µmol/l, p = 0.03)]. MTHFR TT, male gender and protein C predicted age at PVT (p = 0.02, p = 0.04 and p = 0.08); MTHFR TT and Child-Pugh score predicted plasma HC (p = 0.005 and p = 0.01) as well as low plasma protein C (p < 0.0001 and p = 0.0002). Plasma HC inversely related to protein C in the MTHFR TT group (p < 0.0001). Compound MTHFR TT with PT GA had lower age at PVT compared to MTHFR TT alone (49 ± 18 vs 58 ± 12 years). CONCLUSIONS: MTHFR TT anticipates PVT associated with LC by an average of 8 years; MTHFR TT associates with severity of liver disease and to high plasma HC; the latter may contribute to the prematurity of PVT by interfering with the anticoagulant activity of protein C.

Thrombocytopaenia in antiphospholipid syndrome: a free radical perspective.

Thrombosis associated with thrombocytopaenia is an apparent paradox that is present across a wide spectrum of disorders. While thrombocytopaenia has been a controversial clinical classification criterion for APS, as initial reports failed to demonstrate a relation between low platelet count with other clinical or laboratory manifestations of the syndrome, recent data highlight the association between mild-moderate thrombocytopaenia and the risk of thrombosis. Although aPL antibodies may induce platelet activation in vitro, additional stimuli may contribute to their activation in vivo, among which are reactive oxygen and nitrogen species and lipid peroxidation products, which are elevated in patients with APS; an excess of the same stimuli may induce megakaryocyte and platelet apoptosis that leads to decreased platelet production and increased destruction, resulting ultimately in thrombocytopaenia. Herein we provide a novel plausible framework involving free radicals that could add to the understanding of the thrombocytopaenia-thrombosis paradox in APS.

Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis.

We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.

Intima media thickness of carotid arteries in familial Mediterranean fever: a systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis of studies reporting data on atherosclerosis and inflammatory markers in familial Mediterranean fever (FMF). METHODS: EMBASE and PubMed databases were screened according to PRISMA guidelines from inception to January 2022 for articles reporting measurements of the intima media thickness (IMT) of carotid arteries and eventually carotid plaques; random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events were employed. RESULTS: The screening and selection search strategy yielded 18 case controls studies (16 full papers and 2 abstracts); the IMT was greater in FMF (n = 1112) than in controls (n = 901) (p < 0.0001) with wide heterogeneity (I2 = 86.4%); a sensitivity analysis according to mean age of participants, male to female ratio, disease duration, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen (FNG), atherogenic index of plasma (AIP), colchicine use and NOQAS revealed that the heterogeneity variance was partly explained by CRP (p = 0.01) and to a much lesser extent by the AIP (p = 0.10). The pooled prevalence of carotid plaques was greater in FMF (n = 137) than in controls (n = 156) (19% vs 8.3%, p = 0.02) with low heterogeneity. CONCLUSION: FMF is characterised by premature atherosclerosis expressed as a thicker intima media and a greater prevalence of carotid plaques, partially related to the C-reactive protein, as expected by the autoinflammatory nature of FMF. Key Points • Familial Mediterranean fever is characterised by premature atherosclerosis. • C-reactive protein relates to intima media thickness in keeping with the autoinflammatory nature Familial Mediterranean fever. • Targeting the inter-critical low-grade inflammation may be relevant to minimise the additional cardiovascular risk posed by premature atherosclerosis.

Juvenile patients with the homozygous MTHFR C677T genotype develop ischemic stroke 5 years earlier than wild type.

To compare age at 1st ischaemic stroke (IS) in a cohort of juvenile (< 46 years of age) IS patients evaluated for the rs1801133 polymorphism (C → T677) of the methylene tetrahydrofolate reductase (MTHFR) gene; to identify predictors of age at IS and of type of cerebral vessel involvement, small vessel disease (SVD) vs large vessel disease (LVD) responsible for the IS; to evaluate possible associations between other clinical and laboratory variables. Retrospective cohort study on 82 MTHFR TT, 54 MTHFR TC and 34 MTHFR CC participants; data regarding age, sex, age at IS, history of dyslipidaemia, hypertension, smoking, migraine and homocysteine (HC) as well as neuroimaging were collected. Age at IS was lower in MTHFR TT than MTHFR TC and CC (35 ± 4 vs 38 ± 0 vs 40 ± 3 years, respectively, p = 0.002); plasma HC (median, interquartile range) was higher in MTHFR TT than in the other groups [16.7 (11.8, 28.6) vs 11.4 (8.2, 16.1) vs 9.8 (7.9, 1.3) respectively, p < 0.0001)] and was higher in SVD than LVD [17.4 (12.4, 32.5) vs  11.4 (8.8, 16.4) p < 0.0001]. MTHFR TT independently predicted age at IS (p = 0.0008) alongside smoking both as a categorical (p = 0.003) or continuous variable (p = 0.02), whereas HC independently predicted SVD as categorical (p = 0.01) and continuous variable (p < 0.0001). Smoking positively predicted plasma HC (p = 0.005) and negatively the activated partial thromboplastin ratio (aPTTr) (p = 0.02). Juvenile IS carriers of the MTHFR TT genotype develop their 1st occlusion on average 5 years earlier compared to the CC genotype; smoking contributes to this prematurity adversely affecting plasma HC and coagulation whereas plasma HC predicts IS secondary to SVD. Public health campaigns against smoking should highlight the prematurity of IS in the juvenile population.

Plasma Homocysteine in Behcet's Disease: A Systematic Review and Meta-Analysis.

AIM: To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations. METHODS: Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes. RESULTS: The search strategy retrieved 48 case-control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p < 0.0001) with wide heterogeneity (I2 = 89.7%) that remained unchanged after sensitivity analysis according to year of article publication, age of BD participants, study size, study quality, method of HC determination, and male/female ratio >1.5; some pooled ethnicities explained a small part of the heterogeneity (I2 = 16.3%). Active BD participants had higher HC than inactive ones (p < 0.0001), with moderate heterogeneity (I2 = 49.2%) that disappeared after removal of an outlier study with very high disease activity. BD participants with any vascular involvement had higher HC than those without (p < 0.0001) with wide heterogeneity (I2 = 89.7%); subgroup analysis on venous thrombosis only changed neither effect size (p < 0.0001) nor heterogeneity (I2 = 72.7%). BD participants with ocular involvement had higher HC than those without (p < 0.0001) with moderate heterogeneity (I2 = 40.3%). CONCLUSION: Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.

Cardiac and vascular features of arterial and venous primary antiphospholipid syndrome. The multicenter ATHERO-APS study.

BACKGROUND: Patients with primary antiphospholipid syndrome (PAPS) may suffer from venous and/or arterial thrombosis, but studies addressing eventual clinical and laboratory features that may discriminate between arterial thromboembolism (ATE) from venous thromboembolism (VTE) have been poorly addressed. METHODS: Cross sectional comparison of baseline characteristics of 100 patients enrolled in the multi center ATHERO-APS cohort study; patients with previous ATE and VTE were compared with regards to clinical and biochemical variables as well as to echocardiographic features and ankle-brachial index (ABI) measured at enrolment. RESULTS: Mean age of patients was 51 years, 72 were women. 60 patients suffered VTE and 40 ATE. Compared to VTE, ATE patients displayed a higher prevalence of hypertension (43.3% vs. 65%, p = 0.034) and diabetes (3.3% vs. 17.5%, p = 0.015). Mean concentration of inflammation and complement activation markers were similar between the two groups as well as autoantibodies titres; mean D-dimer concentration was greater in VTE patients (184 ng/ml vs. 347 ng/ml; p = 0.024) whereas mean platelet count was greater in ATE patients (263 × 109/L vs 216 × 109/L, p = 0.044). By multivariable logistic regression analysis, adjusted for age, sex, hypertension and diabetes, ABI ≤ 0.9 (OR: 3.4; p = 0.041) and left atrial enlargement (OR: 3.5; p = 0.035) were associated with a history of ATE. ATE patients had a higher prevalence of ABI <0.9 (32.5% vs 10% p = 0.005) than VTE patients. At logistic regression analysis, IgG aCL >120 GPL U/ml was associated with an ABI ≤0.9 (OR: 5; p = 0.023) after adjustment for age and sex. CONCLUSION: Clinical, laboratory and cardiovascular variables distinguish arterial from venous APS patients, amongst which the ABI and left atrial enlargement. Implications for these two distinct clinical phenotypes of APS patients need further investigation.

Homozygous methylentetrahydrofolate reductase C667T genotype anticipates age at venous thromboembolism by one decade.

The aim of the study was to compare age at first venous thromboembolism (VTE), plasma homocysteine and activated partial thromboplastin time ratio (aPTTr) amongst unprovoked VTE patients with the methylentetrahydrofolate reductase (MTHFR) C667T genotypes, and to identify predictors of age at first VTE, of plasma homocysteine and of the aPTTr; to evaluate whether heterozygous or homozygous prothrombin (PT) G20210A mutation lowered the age at first VTE when associated with MTHFR TT. Retrospective cohort study on 259 MTHFR TT, 76 MTHFR TC and 64 MTHFR CC participants with unprovoked VTE; each participant contributed age, sex, age at VTE, history of dyslipidaemia, hypertension, smoking, homocysteine (measured by enzyme immunoassay) and aPTTr (measured by standard coagulation assay). Age at first VTE was lower in MTHFR TT than MTHFR TC and CC (41 ±â€Š14 vs. 50 ±â€Š16 vs. 51 ±â€Š12 years, respectively, P < 0.0001); plasma homocysteine was higher in MTHFR TT than in the other groups (22 ±â€Š21 vs. 12 ±â€Š11.6 vs. 10 ±â€Š3.3 µmol/l, respectively, P = 0.0005) whilst aPTTr was not different. MTHFR TT independently predicted age at first VTE (P = 0.001), plasma homocysteine (P < 0.0001) alongside sex (P = 0.0007), age and smoking (P = 0.03 for both). Compound MTHFR TT with PT GA or AA had no lowering effect on age at first VTE compared with MTHFR TT alone (41 ±â€Š13 vs. 41 ±â€Š14 years). Plasma homocysteine inversely related to aPTTr in the MTHFR TT group (P = 0.003). MTHFR TT anticipates age at first VTE by an average of 10 years compared with MTHFR TC and CC genotypes.

Antiphospholipid Antibodies and Heart Failure with Preserved Ejection Fraction. The Multicenter ATHERO-APS Study.

BACKGROUND: The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. METHODS: A prospective multicenter cohort study including 125 patients was conducted: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP > 220 pg/mL, left atrial (LA) enlargement, increased left ventricular filling pressure. RESULTS: Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE. Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG > 40 GPL (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.09-10.77, p = 0.035), anti ß-2-glycoprotein-I IgG > 40 GPL (OR 5.28, 1.53-18.27, p = 0.009), lupus anticoagulants DRVVT > 1.25 (OR 5.20, 95% CI 1.10-24.68, p = 0.038), and triple positivity (OR 3.56, 95% CI 1.11-11.47, p = 0.033) were associated with HFpEF after adjustment for age and sex. By multivariate analysis, hypertension (OR 19.49, 95% CI 2.21-171.94, p = 0.008), age (OR 1.07, 95% CI 1.00-1.14, p = 0.044), and aß2GPI IgG > 40 GPL (OR 8.62, 95% CI 1.23-60.44, p = 0.030) were associated with HFpEF. CONCLUSION: HFpEF is detectable in a relevant proportion of APS patients. The role of aPL in the pathogenesis and prognosis of HFpEF needs further investigation.

Antiphospholipid Antibodies in Sickle Cell Disease: A Systematic Review and Exploratory Meta-Analysis.

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.