Biochemical Markers with Low-grade Inflammation as Predictors of Thrombotic Events in Antiphospholipid Syndrome

2017 ◽  
Vol 68 (7) ◽  
pp. 1586-1590
Author(s):  
Claudia Gavris ◽  
Vladimir Poroch ◽  
Laurentiu Simion ◽  
Adrian Baracan ◽  
Elena Toader ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Biochemical Markers ◽  
Cumulative Risk ◽  
Low Grade ◽  
Activation Markers ◽  
Acute Thrombosis ◽  
Markers Of Inflammation ◽  
Hs Crp ◽  
Low Grade Inflammation

The study aimed to test the inflammation hypothesis in antiphospholipid syndrome (APS) by assessing biochemical markers of inflammation and platelet activation. Forty one patients with APS were compared to 40 controls. High-sensitivity C-reactive protein (hs-CRP) (as inflammatory biomarker), P-selectin and soluble CD40L (sCD40L) (as platelet activation markers) were measured by ELISA at enrolment and after 12 months follow-up. Serum hs-CRP, P-selectin and sCD40L levels were significantly higher in patients with APS compared to controls. P-selectin was significantly higher in APS patients with recurrent or acute thrombosis compared to APS patients with no recurrent thrombotic events. Serum hs-CRP and anticardiolipin antibodies (aCL) and were independent predictors of thrombosis in APS. In conclusion, persistent increased hs-CRP titres demonstrated low-grade inflammation in APS. Serum biomarkers as aCL and hs-CRP were independent thrombotic cumulative risk predictors in patients with APS.

Reduced antiplatelet effect of aspirin is associated with low-grade inflammation in patients with coronary artery disease

2013 ◽  
Vol 109 (05) ◽  
pp. 920-929 ◽  
Author(s):  
Sanne Larsen ◽  
Erik Grove ◽  
Steen Kristensen ◽  
Anne-Mette Hvas
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Low Grade ◽  
Serum Thromboxane ◽  
Hs Crp ◽  
Artery Disease ◽  
Low Grade Inflammation

SummaryInflammation has been proposed to modify platelet function. This may lead to increased platelet reactivity and reduced antiplatelet drug efficacy in patients with coronary artery disease (CAD). However, this hypothesis has not been investigated in stable CAD patients receiving aspirin as mono antiplatelet therapy. It was the objective of this study to investigate the association between platelet reactivity, the inflammatory markers high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6), and platelet activation. We performed a cross-sectional study on 524 stable high-risk CAD patients. Among these, 91% had a history of myocardial infarction, 23% had type 2 diabetes, and 13% had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet reactivity was assessed by multiple electrode aggregometry (Multiplate®, MEA) and VerifyNow®. Inflammation was evaluated by hs-CRP and IL-6. Platelet activation was assessed by soluble P-selectin (sP-selectin), and cyclooxygenase-1 inhibition was evaluated by measurement of serum thromboxane B2. Hs-CRP levels were significantly higher in upper platelet reactivity tertile patients than in lower platelet reactivity tertile patients (p≤0.02). Similar results were obtained with IL-6, though not statististically significant (p≥0.15). Platelet activation evaluated by sP-selectin was significantly higher in patients with MEA reactivity levels in the upper tertile than in the lower tertile (p=0.0001). Optimal compliance was confirmed by low serum thromboxane B2 levels in all patients. In conclusion, increased levels of hs-CRP were associated with augmented platelet reactivity in stable high-risk CAD patients receiving aspirin as mono antiplatelet therapy. These findings may suggest that chronic low-grade inflammation reduce the antiplatelet effect of aspirin.

Abstract 14849: Gender Differences in Impact of CYP2C19 Polymorphism and Low Grade Inflammation on Coronary Spasm in Patients with Vasospastic Angina (VSA)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomonori Akasaka ◽  
Seiji Hokimoto ◽  
Noriaki Tabata ◽  
Kenji Sakamoto ◽  
Kenichi Tsujita ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Spasm ◽  
Coronary Spasm ◽  
Control Group ◽  
Low Grade ◽  
Cyp2c19 Genotype ◽  
Loss Of Function ◽  
Hs Crp ◽  
The Impact ◽  
Low Grade Inflammation

Background: Several cytochrome P450 (CYP) enzyme families have been identified in extra hepatic tissues such as heart, vasculature, kidney, and lung. CYP2C19 localized in vascular smooth muscle and endothelium contributes to the regulation of vascular tone and homeostasis. However, it is unknown whether CYP2C19 genotype is associated with the vascular tonus in patients with VSA. The aim of this study was to examine the impact of CYP2C19 genotype on coronary artery spasm in patients with VSA. Methods: We examined the distribution of CYP2C19 genotype in patients with VSA (n=129) who were diagnosed by intra-coronary acetylcholine infusion test and healthy subjects (n=455) as control group. CYP2C19 genotypes were divided into 3 groups; (1) CYP2C19*1/*1: EM, (2) one loss-of-function allele (*1/*2, *1/*3: IM), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3: PM). Moreover, we measured the level of high-sensitive CRP (hs-CRP) as a degree of low glade inflammation in each group. Results: The ratios of CYP2C19 genotype (EM, IM, and PM) were 30, 42, and 28% in VSA group, and 32, 49, and 19% in control group. In short, PM frequency was significantly higher in VSA than in control (28% vs 19%, P=0.026). In VSA group, the ratios of CYP2C19 genotype were 36, 44, and 20% in male, and 20, 39, and 41% in female, respectively. Briefly, the PM frequency was significantly higher in female than in male (41% vs 20%, P<0.001). Moreover, the level of hs-CRP was significantly higher in VSA group than in control group (0.17±0.367 vs 0.10.±0.240, P=0.02). When patients were stratified by gender, the level of hs-CRP was significantly higher in VSA group in female (0.11±0.198 vs 0.06±0.105, P=0.031) and male (0.20±0.438 vs 0.12±0.277, P=0.044). Multivariate analysis for coronary spasm indicated high age, hypertension, and high level of hs-CRP as predictive factors among all subjects. PM is a predictive factor for coronary spasm in female group only (OR3.1, 95%RI 1.525-6.317, P=0.002), but not in male (OR0.829, 95%RI 0.453-1.518, P=0.543). Conclusion: The CYP2C19 two loss-of-function alleles (PM) and low grade inflammation may be associated with pathophysiology of coronary artery spasm and the regulation of coronary tonus, especially in female.

Abstract 11600: Long Sleep Duration and Low-Grade Inflammation: New Indicators of Arterial Stiffness in the Japanese at High-risk of Cardiovascular Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Satoshi Niijima ◽  
Michiaki Nagai ◽  
Satoshi Hoshide ◽  
Mami Takahashi ◽  
Masahisa Shimpo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Sleep Duration ◽  
Aortic Stiffness ◽  
The Other ◽  
Low Grade ◽  
Long Sleep ◽  
Hs Crp ◽  
Low Grade Inflammation

Background: Recently, several studies have reported that long sleep duration was independently associated with increased aortic stiffness. On the other hand, high-sensitive C-reactive protein (hs-CRP) was associated with increased aortic stiffness. In this study, the relationships among self-reported sleep duration, hs-CRP and pulse wave velocity (PWV) were investigated in the Japanese at high-risk of cardiovascular disease. In addition, we investigated whether antihypertensive treatment moderated these relationships or not. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, brachial-ankle PWV and hs-CRP measurement were performed in the 2304 patients (64.7 years old, male 49.6%). A self-administered questionnaire included items on daily sleep duration was used. Results: According to the sleep duration (6h or less,6h to 8h,8h or more per night), significant associations of sleep duration were observed with PWV (1594 vs 1644 vs 1763 cm/s, p<0.0001).In the multiple regression analysis adjustment for confounders including age body mass index, total cholesterol, HbA1c and clinic systolic blood pressure (SBP), long sleep duration (8h or more per night) (B: 29, 95%CI: 1.0-56, p<0.05) and log hs-CRP (B: 25, 95%CI: 3.1-48, p<0.05) were significantly positively associated with PWV. A significant interaction was found between long sleep duration and antihypertensive agent non-use for PWV (p<0.05). Especially, in the group without calcium channel blockers (CCBs), long sleep duration was significantly associated with PWV (p<0.01), while a marginal significant synergetic relationship was observed between long sleep duration and log hs-CRP for PWV (p=0.07). On the other hand, there were no significant interactions between long sleep duration and angiotensin receptor blockers non-use. Conclusions: Long sleep duration and hs-CRP were significant indicators of increased PVW in the high-risk Japanese population. In those without CCBs, long sleep duration served as a strong determinant for arterial stiffness, marginally interacted by low-grade inflammation. CCBs use might be important not to aggravate artery remodeling caused by long sleep duration.

Abstract 17996: Is There Gender Differences in Effect of CYP2C19 Polymorphisms or Low-grade Inflammation on Coronary Microvascular Disorder (CMVD)?

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
tomonori akasaka ◽  
Seiji Hokimoto ◽  
Hisao Ogawa
Keyword(s):  
Gender Differences ◽  
Coronary Artery ◽  
Predictive Factors ◽  
Provocation Test ◽  
Low Grade ◽  
Cyp2c19 Genotype ◽  
Loss Of Function ◽  
Significant Difference ◽  
Hs Crp ◽  
Low Grade Inflammation

Background: Specific CYPs localized in vascular smooth muscle and endothelium contribute to the regulation of vascular tone and homeostasis. CYP2C19 poor metabolizer(PM) is reported to be an independent risk factor for coronary artery disease. And, CYP2C19 PM is correlated with an increase in the circulating levels of hs-CRP in female. However, it is unknown whether CYP2C19 genotype is associated with the coronary microvascular disorder (CMVD).So, we examined gender differences in effect of CYP2C19 genotype and low grade inflammation on CMVD. Methods: We examined CYP2C19 genotypes in patients with CMVD (n=54) diagnosed by an intracoronary acetylcholine infusion test, with healthy subjects (n=76) serving as the control. CMVD was defined as the presentation of no coronary artery stenosis in angiography, no epicardial spasms, inversion of lactic acid levels between intracoronary and coronary sinuses in the intracoronary acetylcholine-provocation test, and an adenosine triphosphate-induced CFR<2.5. CYP2C19 genotypes were divided into 3 groups: (1) CYP2C19*1/*1 , extensive metabolizer (EM), (2) one loss-of-function allele (*1/*2, *1/*3; intermediate metabolizer [IM]), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3;[PM]). Results: The ratios of CYP2C19 genotype (EM,IM,and PM) were 31,39,and 30% in CMVD , and 32,49,and 19% in control. There is no significant difference in frequency of CYP2C19 genotype in overall (P=0.146). But, PM frequency was significantly higher in CMVD in only female (34% vs 16%, P=0.042). In level of hs-CRP, there is no significant difference between CMVD and control (0.111±0.080 vs 0.083±0.128,P=0.122), but significantly higher in CMVD in only female (0.112±0.106 vs 0.066±0.106,P=0.002). Moreover, in CMVD, mean of hs-CRP in CYP2C19 PM is significantly higher than that of EM in female (0.115±0.074 vs 0.046±0.039,P=0.034). Multivariate analysis for CMVD indicated that hypertension and chronic kidney disease are predictive factors among all subjects (OR 3.931,P=0.003, OR 3.146,P=0.026). High level of hs-CRP and CYP2C19 PM are predictive factors for CMVD in only female (OR3.864,P=0.047, OR6.079,P=0.042). Conclusion: CYP2C19 PM and low grade inflammation may be associated with CMVD, especially in female.

Abstract 14862: Gender Differences in Impact of CYP2C19 Polymorphism and Low Grade Inflammation on Coronary Microvascular Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomonori Akasaka ◽  
Seiji Hokimoto ◽  
Noriaki Tabata ◽  
Kenji Sakamoto ◽  
Kenichi Tsujita ◽  
...  
Keyword(s):  
Microvascular Disease ◽  
Control Group ◽  
Female Group ◽  
Low Grade ◽  
Cyp2c19 Genotype ◽  
Loss Of Function ◽  
Disease Group ◽  
Hs Crp ◽  
The Impact ◽  
Low Grade Inflammation

Background: Specific CYPs localized in vascular smooth muscle and endothelium contribute to the regulation of vascular tone and homeostasis. CYP2C19 two loss-of-function alleles (PM) were found to be an independent risk factor for diabetic retinopathy, and PM is associated with the coronary spasm especially in female. However, it is unknown whether CYP2C19 genotype is associated with the coronary microvascular disease. The aim was to evaluate the impact of CYP2C19 genotype on coronary microvascular disease. Methods: We examined CYP2C19 genotype in patients with microvascular disease (n=40) who were diagnosed by intra-coronary acetylcholine infusion test and healthy subjects (n=455) as control group. We defined the coronary microvascular disease that have no epicardial spasm and have angina, ischemic ECG changes, reduced coronary blood flow, or inversion of lactic acid level between intra-coronary and coronary sinus. CYP2C19 genotypes were divided into 3 groups; (1) CYP2C19*1/*1: EM, (2) one loss-of-function allele (*1/*2, *1/*3: IM), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3: PM). Results: The ratios of CYP2C19 genotype (EM, IM, and PM) were 33, 35, and 32% in microvascular disease group, and 32, 49, and 19% in control group. In short, PM frequency was significantly higher in microvascular disease group (32%vs19%,P=0.039). In microvascular disease group, the ratios of CYP2C19 genotype (EM, IM, and PM) were 44, 38, and 19% in male, and 25, 33, and 42% in female, respectively. Briefly, the PM frequency was significantly higher in female than in male (42%vs19%,P=0.011). Moreover, the level of hs-CRP was significantly higher in microvascular disease group (0.37±0.908 vs 0.10±0.240, P<0.001). Multivariate analysis for microvascular disease indicated that gender, high age, smoking, hypertension, and the high level of hs-CRP are predictive factors among all subjects. PM is a predictive factor for microvascular disease in female group only (OR3.214, 95%RI 1.286-8.034, P=0.012), but not in male (OR0.909, 95%RI 0.251-3.285, P=0.884). Conclusion: The CYP2C19 two loss-of-function alleles (PM) and low grade inflammation may be associated with pathophysiology of coronary microvascular disease, especially in female.

Prepubertal Children Exposed to Maternal Gestational Diabetes Have Latent Low-Grade Inflammation

2018 ◽  
Vol 90 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Leena Antikainen ◽  
Jarmo Jääskeläinen ◽  
Henrikki Nordman ◽  
Raimo Voutilainen ◽  
Hanna Huopio
Keyword(s):  
Blood Pressure ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Low Grade ◽  
Prepubertal Children ◽  
Glucose And Lipid Metabolism ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Hs Crp ◽  
Low Grade Inflammation

Background: Maternal gestational diabetes mellitus (GDM) and overweight are associated with an increased risk of obesity and the metabolic syndrome in the adult offspring. We studied the influence of maternal GDM on prepubertal children’s height, weight, body mass index (BMI), lipid and glucose metabolism, and low-grade inflammation. Methods: A cohort of 135 prepubertal Caucasian children (age range 4.4–9.7 years) was studied in a controlled cross-sectional study. Seventy-seven children had been exposed to maternal GDM, and 58 children born after a normal pregnancy served as controls. The outcomes were height, weight, BMI, blood pressure, and biochemical markers of glucose and lipid metabolism and inflammation. Results: There were no differences in height, weight, BMI, fasting serum insulin, plasma glucose, lipids, or blood pressure between the study groups. However, high-sensitivity C-reactive protein (hs-CRP) was significantly higher in the GDM group than in the controls (p = 0.001). Conclusions: Higher hs-CRP as a marker of low-grade inflammation was detected in prepubertal children exposed to maternal GDM, but no differences were seen in height, weight, BMI, or markers of glucose and lipid metabolism compared to control children. This finding may reflect an ongoing process of metabolic changes in children born after a GDM pregnancy.

scholarly journals Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

2020 ◽  
Vol 9 (9) ◽  
pp. 3006
Author(s):  
Vadim V. Klimontov ◽  
Anton I. Korbut ◽  
Nikolai B. Orlov ◽  
Maksim V. Dashkin ◽  
Vladimir I. Konenkov
Keyword(s):  
Growth Factors ◽  
Kidney Disease ◽  
Low Grade ◽  
Hs Crp ◽  
Low Grade Inflammation ◽  
Egfr Decline ◽  
Multiplex Bead ◽  
Circulating Cytokines

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; albuminuria and eGFR <60 mL/min/1.73 m2. Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines.

The Effect of BIBT 986, a Novel Small Molecule Dual Inhibitor of Thrombin and Factor Xa, on Coagulation in a Model of Endotoxin Induced, Tissue Factor Triggered Coagulation Activation in Humans.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 912-912 ◽  
Author(s):  
Bernd Jilma ◽  
Judith M. Leitner ◽  
Francesco Cardona ◽  
Florian B. Mayr ◽  
Christa Firbas ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Platelet Activation ◽  
Thrombin Generation ◽  
Anticoagulant Activity ◽  
Thrombin Time ◽  
Coagulation Activation ◽  
Dual Inhibitor ◽  
Activation Markers ◽  
Markers Of Inflammation ◽  
Prolonged Aptt

Abstract Background: BIBT 986 is a novel potent anticoagulant that dually inhibits Factors Xa and IIa. We hypothesized that BIBT 986 would dose-dependently decrease endotoxin-induced, tissue factor triggered coagulation activation. Hence it was the aim of the study to compare with placebo the anticoagulant activity of three dosages of BIBT 986 on parameters of coagulation, platelet activation and inflammation and to examine the safety of BIBT 986 in this setting. Methods: This study was a prospective, randomized, double-blind, placebo-controlled, parallel-group dose escalation trial in 48 healthy male volunteers. Participants were randomised to receive bolus primed continuous infusions of one of the three doses of BIBT 986 or placebo. All of them received a bolus infusion of 2ng/kg body weight lipopolysaccharide (LPS). Results: BIBT dose-dependently increased anti-Xa activity, activated partial thromboplastin time (APTT), ecarin clotting time (ECT), thrombin time (TT) and the international normalisation ratio (INR). Importantly, BIBT 986 dose-dependently blocked the LPS-induced coagulation as assessed by the in vivo markers of thrombin generation and action: BIBT 986 doses that prolonged APTT by 25% were already effective. The BIBT dose that prolonged APTT by 100%, completely suppressed the increase in prothrombin fragment (F1+2), thrombin-antithrombin complexes (TAT) and D-dimer. BIBT 986 had no influence on activation markers of inflammation, fibrinolysis, endothelial or platelet activation. Conclusion: Infusion of BIBT 986 was safe and well tolerated. BIBT 986 specifically and dose-dependently blocked LPS-induced, tissue factor trigger coagulation. When compared to different anticoagulants tested previously in this standardized model, BIBT 986 was more effective in suppressing thrombin generation (F1+2 levels) than standard doses of danaparoid, dalteparin or lepirudin. BIBT 986 represents the first drug of a new class of dual FXa and FIIa inhibitors, and displays high potency.

Antibodies Against Platelet Glycoprotein Target Antigens in Antiphospholipid Syndrome (APS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3973-3973 ◽  
Author(s):  
Carlos J. Bidot ◽  
Wenche Jy ◽  
Carlos Bidot ◽  
Lawrence L. Horstman ◽  
Vincenzo Fontana ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Endothelial Activation ◽  
Platelet Glycoprotein ◽  
Activation Markers ◽  
Positive Group ◽  
Platelet Antibodies ◽  
Platelet Microparticles

Abstract Introduction: Antiphospholipid syndrome (APS) is characterized clinically by thrombotic events and the presence of antiphospholipid antibodies (aPLA) and/or lupus anticoagulant (LA). It is frequently associated with thrombocytopenia and anti-platelet antibodies have been implicated by some. However the roles of anti-platelet antibodies in APS have not been elucidated. We previously reported that platelet activation, but not endothelial activation, was associated with thrombosis in aPLA+ patients [Blood, 104:143a, 2004] but the cause of platelet activation was not addressed. In the present study, we investigated the prevalence of anti-platelet antibodies in APS patients, as well as platelet and endothelial activation. Material and Methods: We evaluated 47 patients with primary APS. Anti-platelet antibodies against GP IIb/IIIa (CD41b), GP Ib/IX (CD 42b) and GP IV (CD36) for IgG and IgM class were measured by PAICA assay [Thromb Haemost76:1820, 1996]. We also measured platelet and endothelial activation markers by flow cytometry: CD62P on platelets, CD31+/CD42+ platelet microparticles (PMP), and CD31+/CD42- endothelial microparticles (EMP). Results: Of the 47 patients, 34 (72%) were positive for at least one anti-platelet antibody. Looking first at IgG, 18/34 (53%) were positive for GP IV; 17/34 (50%) for GP IIb/IIIa; and 16/34 (47%) for GP Ib/IX. IgM antibodies were 47% (14/30) for GP Ib/IX, 38%(13/34) for GP IIb/IIIa, and 24% (8/33) for GP IV. Platelet and endothelial markers were significantly more common in the anti-platelet antibodies positive group: 40% vs. 21% for CD62P, 40% vs. 28.5% for EMP, and 23% vs. 5% for PMP, respectively. We found that CD62P associated significantly with IgM anti-GP IIb/IIIa (p< 0.05), and PMP with IgM anti-GP IIb/IIIa (p< 0.05), and IgM anti-GP IV (p< 0.05). Conclusions: Anti-platelet antibodies are common in APS, confirming previous reports. We found that anti-platelet antibodies IgM anti-GP IIb/IIIa, and IgM anti-GP IV were often associated with platelet activation, suggesting that these antibodies may activate platelets to play an important role in the thrombogenesis of APS. These antibodies were also associated with endothelial activation. It remains to be determined which antibodies, APLA and/or anti-platelet antibodies, play a dominant role in the activation of platelet or endothelial cells and contibute most to the pathogenesis of thrombosis in APS.

Non-Transferrin-Bound Iron, Iron Load and Hypoxia May Induce Low-Grade Inflammation in Patients with Thalassemia Intermedia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4072-4072
Author(s):  
Antonios Kattamis ◽  
Emmanuel Kanavakis ◽  
Vassilios Ladis ◽  
Christos Kattamis ◽  
Ioannis Papassotiriou
Keyword(s):  
Clinical Chemistry ◽  
Graphite Furnace ◽  
Heme Iron ◽  
Tissue Hypoxia ◽  
Low Grade ◽  
Thalassemia Intermedia ◽  
Transfusion Therapy ◽  
Inflammatory Status ◽  
Hs Crp ◽  
Low Grade Inflammation

Abstract Abstract 4072 Poster Board III-1007 Background Inflammation is known to play an important role in the pathogenesis of thalassemia. Serum levels of pro-inflammatory cytokines such as IL-6 and TNF-a are known to be elevated in thalassemic patients, suggestive a low-grade inflammatory status. These levels are comparable to the ones observed in patients with diabetes, obesity and atherosclerosis. Altered redox status has also been shown in thalassemic erythrocytes. Reactive oxygen species (ROS) are generated in increased amounts after the precipitation of excess unmatched globin chains, the deposition of non-heme iron and hemichromes and the induced inflammation. In this study we assessed the levels and possible causes of inflammatory status in patients with thalassemia intermedia (TI). Patients and Methods Thirty-five patients with TI, 13 men and 22 women, aged 8-63 years were included in the study. None of the patients had received any transfusion therapy for at least 6 months prior of sampling, while 25/35 patients had been splenectomized. We measured the hematologic and biochemical parameters, including Hb, HbF ferritin and soluble transferrin receptors (sTfR) with standard methodology. Serum concentrations of non-transferrin bound iron (NTBI) were estimated using graphite furnace atomic absorption spectrometry. Determination of high-sensitivity CRP (hs-CRP or cardiophase-CRP) was performed using the Siemens Advia 1800 Clinical Chemistry System. Furthermore, we obtained P50 values from oxygen equilibrium curves (OEC) drawn in fresh whole blood. Oxygen delivery and release parameters were calculated using the “Siggaard–Andersen's Oxygen Status Algorithm”. Results hs-CRP levels were elevated 2.12±0.55 mg/L compared to lean control values 1.2±0.19 mg/L (p<0.008). Most of the patients (60 %) showed evidence of low-grade inflammation based on the hs-CRP levels. NTBI levels were significantly elevated (2.4±2.2micromol/L), with only 10/30 patients having levels <0.5micromol/L, which is proposed as normal limit. As accepted P50 values were indicative of relative tissue hypoxia (all patients demonstrate increase oxygen affinity). All of the patients showed evidence of increased eryhtropoeitic activity, as indicate by the elevated sTfR levels ranged from 4.0 to 22.9mg/L (3- to 19-fold increase of erythroid marrow activity). The main results of the evaluated correlations showed that: a) hs-CRP levels correlated positively with NTBI concentrations (r=0.741, p<0.0001), b) hs-CRP levels correlated positively with ferritin levels (r=0.522, p=0.004) and c) hs-CRP levels correlated negatively with P50 values (r=-0.409, p=0.03), while no correlation was found between hs-CRP levels and the degree of ineffective erythropoiesis expressed as sTfR concentrations (p> 0.223). Conclusions These findings demonstrate that patients with TI have a chronic low-grade inflammation. Similar inflammatory status has been also shown in patients with atherosclerosis, diabetes and obesity. The level of inflammation correlated with indexes of iron homoestasis, alteration of which is commonly observed in patients with TI. Thus, it seems plausible that the oxidative effects of NTBI and increased iron burden result in chronic inflammation in these patients. The observed negative correlation of inflammation and P50 is of interest, as it indicates possible involvement of tissue hypoxia in inflammation processes. Disclosures: Kattamis: Novartis: Consultancy, Honoraria, Speakers Bureau.

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