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Fabiola Traina - One of the best experts on this subject based on the ideXlab platform.
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elevated hypercoagulability markers in Hemoglobin SC Disease
Haematologica, 2015Co-Authors: Marina Pereira Colella, Erich Vinicius De Paula, Joao Agostinho Machadoneto, Nicola Conran, Joyce M Annichinobizzacchi, Fernando F Costa, Fabiola Traina, Sara Teresinha Olalla SaadAbstract:Hemoglobin SC Disease is a very prevalent Hemoglobinopathy; however, very little is known about this condition specifically. There appears to be an increased risk of thromboembolic events in Hemoglobin SC Disease, but studies evaluating the hemostatic alterations are lacking. We deSCribe the findings of a cross-sectional observational study evaluating coagulation activation markers in adult patients with Hemoglobin SC, comparing them with those in sickle cell anemia patients and healthy controls. A total of 56 Hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients was taking hydroxyurea. Hemoglobin SC patients had a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (P<0.01). Hemoglobin SC patients had lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (P<0.05). Markers of endothelial activation (soluble thrombomodulin and soluble vaSCular cell adhesion molecule-1) and inflammation (tumor necrosis factor-alpha) were both significantly elevated in Hemoglobin SC patients when compared to controls, being as high as the levels seen in patients with sickle cell anemia. Overall, in Hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in Hemoglobin SC Disease: retinopathy and osteonecrosis. In summary, our results demonstrate that Hemoglobin SC patients have a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia.
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increased inflammatory markers and their correlations to clinical complications in Hemoglobin SC Disease
Blood, 2013Co-Authors: Marina Pereira Colella, Erich Vinicius De Paula, Joao Agostinho Machadoneto, Nicola Conran, Joyce M Annichinobizzacchi, Fernando Ferreira Costa, Susan Kelly Picoli Quaino, Sara Terezinha Olallasaad, Fabiola TrainaAbstract:Hemoglobin SC (HbSC) Disease is the second most prevalent Hemoglobinopathy after sickle cell anemia (SCA – homozygous HbSS). Despite its high prevalence, most of the knowledge about the pathophysiology of HbSC is inferred from studies focused primarily on SCA. In general, HbSC is considered a milder form of SCA. Chronic inflammatory activity is clearly seen in SCA, but not much is known about the inflammation present in HbSC. In the present study we aimed to evaluate inflammatory markers in HbSC patients and their associations with clinical and laboratory characteristics of the Disease. This was a cross-sectional study performed on a cohort of 56 HbSC patients (mean age of 41 years), 39 SCA patients (mean age of 34 years), and 24 healthy age-matched controls. All of the patients were in steady state, with no history of painful crisis, hospitalization or transfusions during the preceding 3 months. None of the patients were in use of hydroxyurea. We evaluated the inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL8). Levels of inflammatory markers were correlated with hemolysis markers, blood counts, coagulation markers (tissue factor expression [TF], thrombin-antithrombin complex [TAT], d-dimer [DD]) and endothelial activation marker (soluble thrombomodulin [sTM]). TNF-α, IL8, TAT, DD and sTM were all measured by ELISA. Leukocyte TF mRNA expression was analyzed by real time quantitative PCR. Statistical analyses were performed by Mann-Whitney’s U test and Spearman’s rank correlation test. HbSC patients presented higher TNF-α levels than those of controls (2.72 vs. 0 pg/mL; P vs . 2.74 pg/mL; P = 1.0). IL8 levels were similar between HbSC patients and controls (2.54 vs. 2.29 pg/mL; P = 0.16) and also similar between HbSC and SCA patients (2.54 vs. 2.82 pg/mL; P = 0.45). In the analyses of the HbSC cohort, IL8 levels presented significant positive correlations with: leukocyte (r=0.4; P =0.02), monocyte (r=0.5; P =0.001), and platelet counts (r=0.6; P =0.0002); and hemolysis markers: indirect bilirubin (r=0.4; P =0.04) and lactate dehydrogenase levels (r=0.4, P =0.04). TNF-α levels presented no significant correlations with laboratory markers. We also evaluated associations between IL8 and TNF-α levels and clinical complications; stroke, pulmonary arterial hypertension, acute thoracic syndrome, retinopathy, osteonecrosis, leg ulcers and autosplenectomy. HbSC patients with osteonecrosis had significantly higher IL8 levels (3.8 vs. 2.4; P =0.01) when compared with patients without this complication. IL8 levels were also higher in patients with autosplenectomy (3.8 vs. 2.0; P =0.0003). Our results indicate that HbSC Disease patients present elevation of inflammation markers, similar to alterations seen in SCA. In our cohort, patients with higher peripheral blood counts and a more intense hemolytic activity, such as patients with autoesplenectomy, have higher levels of inflammatory markers. Our data suggest that inflammation may be a factor contributing to the pathophysiology of a very prevalent chronic complication of HbSC Disease, osteonecrosis. Studies focusing on the pathophysiology of HbSC Disease are lacking, and in view of the high prevalence of this Disease we believe it should be the focus of future studies. DiSClosures: No relevant conflicts of interest to declare.
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elevation of hypercoagulability markers in Hemoglobin SC Disease
Blood, 2012Co-Authors: Marina Pereira Colella, Erich Vinicius De Paula, Joao Agostinho Machadoneto, Nicola Conran, Joyce M Annichinobizzacchi, Sara Teresinha Olalla Saad, Fernando Ferreira Costa, Susan Kelly Picoli Quaino, Fabiola TrainaAbstract:Abstract 3227 Background: Sickle cell anemia (SCA) patients present an elevated rate of thrombotic complications and increased biological markers of hemostatic activation. Hemoglobin SC Disease (HbSC) is the second most prevalent Hemoglobinopathy after SCA (homozygous HbSS), has specific clinical and pathological characteristics that may differ from SCA, and viSCosity appears to be a hallmark of the Disease. Studies have shown an increase in thrombotic events in HbSC patients, especially pulmonary embolism, however, not much is known about the coagulation activation in this population. We herein aimed to evaluate the hypercoagulability markers in HbSC Disease and their associations with patients9 clinical and laboratory characteristics. Patients and Methods: This was a cross-sectional study performed on a cohort of 41 adult HbSC (mean age of 43 years) and 58 adult HbSS patients (mean age of 36 years), all in steady-state, and 25 healthy age-matched controls. We evaluated the expression of tissue factor (TF), the physiological initiator of coagulation, and thrombin-antithrombin complex (TAT), a final marker of coagulation activation. Leukocyte TF mRNA expression was analyzed by real time quantitative PCR and TAT plasma levels were measured by ELISA. Comparisons between the two patient groups and controls were performed using Kruskal-Wallis test followed by Dunn9s Multiple Comparisons test. Fisher9s exact test and Mann-Whitney9s U test were used to compare patients9 clinical complications and laboratory characteristics. Spearman9s rank test was used for correlations analysis. Results: Relative TF mRNA expression was significantly up-regulated in HbSC patients when compared to controls (2.6 vs. 1.2), however levels of TF were lower in HbSC than HbSS patients (2.6 vs. 3.3) ( P TF expression, TAT plasma levels were also higher in HbSC patients in comparison to controls (4.2 vs. 2.4), and lower in HbSC than HbSS patients (4.2 vs. 7.3); ( P P =0.001), monocyte (r=0.4; P =0.01), and platelet counts (r=0.5; P =0.002); and hemolysis markers: reticulocyte counts (r=0.4; P =0.01) and lactate dehydrogenase levels (r=0.6, P =0.0001). We also evaluated associations between TAT levels and clinical complications: stroke, pulmonary arterial hypertension, acute thoracic syndrome, retinopathy, osteonecrosis, leg ulcers, autosplenectomy and microalbuminuria. HbSC patients with retinopathy had significantly higher TAT levels (4.7 vs. 3.9; P =0.03) when compared with patients without this complication. TAT levels were also higher in patients with autosplenectomy (4.8 vs. 3.8; P =0.004), and in patients with osteonecrosis, although this had borderline statistical significance (4.6 vs. 3.9; P =0.06). TF expression significantly correlated with monocyte counts (r=0.6; P =0.01). Conclusions: Our results indicate that HbSC Disease patients present elevated coagulation activation markers when compared to controls, although not as intense as seen in SCA. Thrombotic complications in HbSC patients have been mainly linked to the hyperviSCosity present in this Disease. Our data suggest that inflammation and hemolysis are also important factors contributing to hemostatic activation, which may participate in the pathophysiology of very prevalent chronic complications of HbSC Disease: retinopathy and osteonecrosis. Interestingly, in our cohort, patients with autosplenectomy had higher levels of pro-coagulant markers, possibly due to a higher intravaSCular hemolytic rate and elevated peripheral blood counts. Although HbSC Disease is considered a milder form of SCA, autopsy studies have shown that mortality by pulmonary embolism is more frequent in HbSC Disease than in SCA, being the second cause of mortality in these patients (Manci et al, 2003). Studies addressing the pathophysiology of coagulation activation in HbSC Disease are lacking. Low numbers of cases of HbSC Disease are usually included in studies focusing mainly in SCA, and the results are very variable, probably due to the small numbers of patients. In view of the high prevalence and morbimortalilty of thrombotic complications in this population, we believe that future studies should focus on a better understanding of hypercoagulability in HbSC Disease. DiSClosures: No relevant conflicts of interest to declare.
Eugene P Orringer - One of the best experts on this subject based on the ideXlab platform.
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hypercoagulability in sickle cell Disease a curious paradox
The American Journal of Medicine, 2003Co-Authors: Kenneth I Ataga, Eugene P OrringerAbstract:Abstract There is evidence of activation of both blood coagulation and platelets in sickle cell Disease. For example, plasma samples obtained in the steady state and during painful crisis demonstrate high levels of thrombin generation, depletion of anticoagulant proteins, and abnormal activation of the fibrinolytic system. Similarly, exposure of surface markers such as CD62P and CD40L, along with increased circulating levels of thrombospondin, signal platelet activation. In addition to its effects on the cleavage of fibrinogen and its ability to activate platelets, the increase in circulating thrombin levels, with its wide-ranging effects on endothelial cells and blood vessels, may be important in the pathophysiology of sickle cell Disease. Therefore, treatments that could decrease thrombin generation or platelet activation may be beneficial in both the treatment of sickle cell Disease and the prevention of complications that characterize this genetic disorder. This review diSCusses hypercoagulability in the various forms of sickle cell Disease, including homozygous sickle cell anemia, Hemoglobin SC Disease, Hemoglobin SD Disease, and sickle cell–β-thalassemia.
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splenic sequestration and multiorgan failure as the presenting manifestation of Hemoglobin SC Disease
The American Journal of the Medical Sciences, 1996Co-Authors: Spencer H Shao, Eugene P OrringerAbstract:Acute splenic sequestration, a well recognized complication of the various sickle cell syndromes, is characterized by increasing splenomegaly and a sudden fall in Hemoglobin concentration. In this article, the authors deSCribe a 21-year-old woman with previously undiagnosed Hemoglobin SC Disease whose initial presentation was that of acute, severe splenic sequestration. Despite the severity of her illness, prompt diagnosis and appropriate therapy led to a complete recovery. The splenic sequestration in this case was apparently exacerbated by a recent hepatitis B infection. To date, this presentation of Hemoglobin SC Disease has not been deSCribed in the medical literature.
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case report splenic sequestration and multiorgan failure as the presenting manifestation of Hemoglobin SC Disease
The American Journal of the Medical Sciences, 1996Co-Authors: Spencer H Shao, Eugene P OrringerAbstract:Acute splenic sequestration, a well recognized complication of the various sickle cell syndromes, is characterized by increasing splenomegaly and a sudden fall in Hemoglobin concentration. In this article, the authors deSCribe a 21-year-old woman with previously undiagnosed Hemoglobin SC Disease whose initial presentation was that of acute, severe splenic sequestration. Despite the severity of her illness, prompt diagnosis and appropriate therapy led to a complete recovery. The splenic sequestration in this case was apparently exacerbated by a recent hepatitis B infection. To date, this presentation of Hemoglobin SC Disease has not been deSCribed in the medical literature.
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case report splenic infarction and acute splenic sequestration in adults with Hemoglobin SC Disease
The American Journal of the Medical Sciences, 1991Co-Authors: Eugene P Orringer, Vance G Fowler, Catrell M Owens, Adrena E Johnson, Matthew A Mauro, Frederic G Dalldorf, Robert D CroomAbstract:While acute splenic sequestration and splenic infarction are commonly observed in infants and young children with sickle cell anemia, they are rarely experienced by adult Hemoglobin S homozygotes because the recurrent splenic infarction that takes place during childhood is typically followed by SCarring, atrophy, and splenic fibrosis. Both acute splenic sequestration and splenic infarction do remain relatively common in adults with the other sickle Hemoglobinopathies. These episodes are almost certainly a consequence of the persistently enlarged and distensible spleens that often remain present in these conditions. In this report, the authors deSCribe two adult patients with Hemoglobin SC Disease: one who developed acute splenic sequestration and one with splenic infarction. In neither case was there a history of recent air travel or exposure to altitude. The clinical course of these two syndromes is presented, and the hematologic, radiologic, and pathologic manifestations are diSCussed. Because they can sometimes be difficult to distinguish from one another, and because a failure to identify acute splenic sequestration can be catastrophic, these two entities must be included in the differential diagnosis for any Hemoglobin SC patient who present with an unexplained fall in Hemoglobin, left upper quadrant pain, unexplained fever, or symptomatic splenomegaly.
Monica L Hulbert - One of the best experts on this subject based on the ideXlab platform.
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higher than expected prevalence of silent cerebral infarcts in children with Hemoglobin SC Disease
Blood, 2015Co-Authors: Kristin P Guilliams, Melanie E Fields, Monica L HulbertAbstract:To the editor: Individuals with Hemoglobin (Hb) SC Disease have fewer vaso-occlusive events and greater life expectancy than those with Hb SS, and they have been excluded from most interventional clinical trials. Although the 10% prevalence of overt stroke and >35% prevalence of silent cerebral
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abstract w mp111 prevalence and risk factors of silent cerebral infarcts in children with Hemoglobin SC Disease
Stroke, 2014Co-Authors: Kristin P Guilliams, Jennifer Sun, Monica L HulbertAbstract:Background: Hemoglobin (Hb) SC Disease comprises 22% of all sickle Hemoglobinopathies and is the second most common form of sickle cell Disease. Silent cerebral infarcts (SCI) are common in Hb SS Disease and are associated with male sex, higher systolic blood pressure (SBP), and lower baseline Hb concentration among children with Hb SS. However, SCI prevalence and risk factors are less well characterized in Hb SC Disease. We tested the hypothesis that risk factors for SCI in Hb SC and Hb SS are similar. Methods: Retrospective chart review of children with Hb SC seen at St. Louis Children’s Hospital (SLCH) Sickle Cell Clinic 2004-2012 who had brain magnetic resonance imaging (MRI) available. At SLCH, all children with sickle cell Disease undergo SCreening brain MRI after their 6th birthday; additional MRIs are obtained for concerning symptoms. Cerebral infarctions were identified as T2- or FLAIR-weighted hyperintensities identified in at least 2 planes or decreased diffusion; silent infarcts were diagnosed...
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silent cerebral infarctions in children and adoleSCents with Hemoglobin SC Disease
Blood, 2012Co-Authors: Jennifer Sun, Monica L HulbertAbstract:Abstract 1011 Background Children with sickle cell Disease (SCD), especially sickle cell anemia, are at high risk of overt and silent cerebral infarctions, leading to physical and cognitive deficits. Less is known about the risks of cerebral infarction in children with Hemoglobin SC (Hb SC). Prior studies have found a prevalence of silent cerebral infarction of 5.8% 1 to 46% 2 in children with Hb SC Disease. We sought to define the prevalence of cerebral infarctions in a population of children and adoleSCents with Hb SC Disease, and to identify medical risk factors for cerebral infarctions. Methods Since 2006, SCreening brain magnetic resonance imaging (MRI) exams have been performed on all children with SCD followed at St. Louis Children9s Hospital at approximately age 6 years. Furthermore, brain MRI is performed if patients present with possible stroke symptoms, such as severe headache, visual changes, weakness, or seizures. Cerebral infarctions were defined as T2- or FLAIR-weighted hyperintensities visible in at least 2 planes; silent infarcts were diagnosed when the patient had no neurological symptoms that correlated with the infarct lesions. Human Studies Committee approval and waiver of consent was obtained prior to reviewing all brain MRIs from children with Hb SC Disease. SPSS version 20 was used for statistical analysis. Results Between January 2004 and May 2012, 95 children and adoleSCents with Hb SC Disease underwent brain MRI; 54% were male. Forty-nine children (51.6%) had no neurological symptoms at the time of the initial MRI; of the 46 children with neurological symptoms, poor SChool performance (16 children, 16.8%) and headaches (15 children, 15.8%) were cited most commonly. Neurological symptoms provoking MRI included unilateral hearing loss (2 children) and Bell9s palsy (3 children). Prevalence of silent infarctions was 14.7% (14/95 children). Seven (50%) of subjects with silent infarctions were male. The mean age at identification of cerebral infarction was 11.9 years (range, 6.2–19.3 years). Five of the infarctions were identified by SCreening asymptomatic children. Nine children were found to have infarctions while experiencing neurological symptoms; in all cases, the infarct lesions did not explain the presenting neurological symptoms. Among 84 children with initial MRIs that were free of infarctions, 3 developed silent cerebral infarctions subsequently. There was no association between silent cerebral infarctions and a history of asthma, headaches, SChool difficulties, or SChool failure. In all cases, the silent cerebral infarctions were located in periventricular, frontal, or parietal white matter; there were no lobar strokes identified. Infarcts ranged in size from 1 mm to 1 cm. All children with silent cerebral infarctions were referred for neurocognitive testing and evaluation for an individualized educational plan. Ten of the 14 children with silent infarctions have had followup MRIs, ranging from 0.1 to 6.4 years following the initial MRI. None have had progressive silent infarct lesions or overt strokes. Magnetic resonance angiography (MRA) was performed in 83 subjects. None of the children had arterial stenosis or occlusion, moyamoya, or aneurysms. Five subjects had subtle irregularities of cerebral arteries noted on MRA, but none progressed to more severe abnormalities. Conclusion Approximately 15% of children and adoleSCents with Hb SC Disease in this retrospective cohort have silent cerebral infarctions, a much higher prevalence than was found in the Cooperative Study of Sickle Cell Disease. 1 The prevalence is lower than that of Steen et al9s cohort, 2 perhaps due to the fact that our center SCreens all SChool-aged children. Clinically significant angiographic abnormalities were not identified in this cohort. Children with silent cerebral infarctions should be referred for neurocognitive testing. Further work is needed to define risk factors and treatments for children with silent cerebral infarctions in Hb SC Disease. DiSClosures: No relevant conflicts of interest to declare.
Nicola Conran - One of the best experts on this subject based on the ideXlab platform.
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elevated hypercoagulability markers in Hemoglobin SC Disease
Haematologica, 2015Co-Authors: Marina Pereira Colella, Erich Vinicius De Paula, Joao Agostinho Machadoneto, Nicola Conran, Joyce M Annichinobizzacchi, Fernando F Costa, Fabiola Traina, Sara Teresinha Olalla SaadAbstract:Hemoglobin SC Disease is a very prevalent Hemoglobinopathy; however, very little is known about this condition specifically. There appears to be an increased risk of thromboembolic events in Hemoglobin SC Disease, but studies evaluating the hemostatic alterations are lacking. We deSCribe the findings of a cross-sectional observational study evaluating coagulation activation markers in adult patients with Hemoglobin SC, comparing them with those in sickle cell anemia patients and healthy controls. A total of 56 Hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients was taking hydroxyurea. Hemoglobin SC patients had a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (P<0.01). Hemoglobin SC patients had lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (P<0.05). Markers of endothelial activation (soluble thrombomodulin and soluble vaSCular cell adhesion molecule-1) and inflammation (tumor necrosis factor-alpha) were both significantly elevated in Hemoglobin SC patients when compared to controls, being as high as the levels seen in patients with sickle cell anemia. Overall, in Hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in Hemoglobin SC Disease: retinopathy and osteonecrosis. In summary, our results demonstrate that Hemoglobin SC patients have a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia.
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increased circulating pedf and low sicam 1 are associated with sickle cell retinopathy
Blood Cells Molecules and Diseases, 2015Co-Authors: Pedro Rodrigues Souza Cruz, Nicola Conran, Farid Menaa, Rodrigo Pessoa Cavalcanti Lira, S Pereira A C Filho, Bruno Batista De Souza, F N Mitsuushi, Kleber Yotsumoto Fertrin, Jose Paulo Cabral De Vasconcellos, Fernando Ferreira CostaAbstract:Sickle cell retinopathy (SCR) develops in up to 30% of sickle cell Disease patients (SCD) during the second decade of life. Treatment for this affection remains palliative, so studies on its pathophysiology may contribute to the future development of novel therapies. SCR is more frequently observed in Hemoglobin SC Disease and derives from vaso-occlusion in the microvaSCulature of the retina leading to neovaSCularization and, eventually, to blindness. Circulating inflammatory cytokines, angiogenic factors, and their interaction may contribute to the pathophysiology of this complication. Angiopoietin (Ang)-1, Ang-2, soluble vaSCular cell adhesion molecule-1, intercellular adhesion molecule (ICAM)-1, E-selectin, P-selectin, IL1-β, TNF-α, pigment epithelium derived factor (PEDF) and vaSCular endothelial growth factor plasmatic levels were determined in 37 SCD patients with retinopathy, 34 without retinopathy, and healthy controls. We observed that sICAM-1 is significantly decreased, whereas PEDF is elevated in HbSC patients with retinopathy (P=0.012 and P=0.031, respectively). Ang-1, Ang-2 and IL1-β levels were elevated in SCD patients (P=0.001, P<0.001 and P=0.001, respectively), compared to controls, and HbSS patients presented higher levels of Ang-2 compared to HbSC (P<0.001). Our study supports the possible influence of sICAM-1 and PEDF on the pathophysiology of retinal neovaSCularization in SCD patients.
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increased inflammatory markers and their correlations to clinical complications in Hemoglobin SC Disease
Blood, 2013Co-Authors: Marina Pereira Colella, Erich Vinicius De Paula, Joao Agostinho Machadoneto, Nicola Conran, Joyce M Annichinobizzacchi, Fernando Ferreira Costa, Susan Kelly Picoli Quaino, Sara Terezinha Olallasaad, Fabiola TrainaAbstract:Hemoglobin SC (HbSC) Disease is the second most prevalent Hemoglobinopathy after sickle cell anemia (SCA – homozygous HbSS). Despite its high prevalence, most of the knowledge about the pathophysiology of HbSC is inferred from studies focused primarily on SCA. In general, HbSC is considered a milder form of SCA. Chronic inflammatory activity is clearly seen in SCA, but not much is known about the inflammation present in HbSC. In the present study we aimed to evaluate inflammatory markers in HbSC patients and their associations with clinical and laboratory characteristics of the Disease. This was a cross-sectional study performed on a cohort of 56 HbSC patients (mean age of 41 years), 39 SCA patients (mean age of 34 years), and 24 healthy age-matched controls. All of the patients were in steady state, with no history of painful crisis, hospitalization or transfusions during the preceding 3 months. None of the patients were in use of hydroxyurea. We evaluated the inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL8). Levels of inflammatory markers were correlated with hemolysis markers, blood counts, coagulation markers (tissue factor expression [TF], thrombin-antithrombin complex [TAT], d-dimer [DD]) and endothelial activation marker (soluble thrombomodulin [sTM]). TNF-α, IL8, TAT, DD and sTM were all measured by ELISA. Leukocyte TF mRNA expression was analyzed by real time quantitative PCR. Statistical analyses were performed by Mann-Whitney’s U test and Spearman’s rank correlation test. HbSC patients presented higher TNF-α levels than those of controls (2.72 vs. 0 pg/mL; P vs . 2.74 pg/mL; P = 1.0). IL8 levels were similar between HbSC patients and controls (2.54 vs. 2.29 pg/mL; P = 0.16) and also similar between HbSC and SCA patients (2.54 vs. 2.82 pg/mL; P = 0.45). In the analyses of the HbSC cohort, IL8 levels presented significant positive correlations with: leukocyte (r=0.4; P =0.02), monocyte (r=0.5; P =0.001), and platelet counts (r=0.6; P =0.0002); and hemolysis markers: indirect bilirubin (r=0.4; P =0.04) and lactate dehydrogenase levels (r=0.4, P =0.04). TNF-α levels presented no significant correlations with laboratory markers. We also evaluated associations between IL8 and TNF-α levels and clinical complications; stroke, pulmonary arterial hypertension, acute thoracic syndrome, retinopathy, osteonecrosis, leg ulcers and autosplenectomy. HbSC patients with osteonecrosis had significantly higher IL8 levels (3.8 vs. 2.4; P =0.01) when compared with patients without this complication. IL8 levels were also higher in patients with autosplenectomy (3.8 vs. 2.0; P =0.0003). Our results indicate that HbSC Disease patients present elevation of inflammation markers, similar to alterations seen in SCA. In our cohort, patients with higher peripheral blood counts and a more intense hemolytic activity, such as patients with autoesplenectomy, have higher levels of inflammatory markers. Our data suggest that inflammation may be a factor contributing to the pathophysiology of a very prevalent chronic complication of HbSC Disease, osteonecrosis. Studies focusing on the pathophysiology of HbSC Disease are lacking, and in view of the high prevalence of this Disease we believe it should be the focus of future studies. DiSClosures: No relevant conflicts of interest to declare.
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elevation of hypercoagulability markers in Hemoglobin SC Disease
Blood, 2012Co-Authors: Marina Pereira Colella, Erich Vinicius De Paula, Joao Agostinho Machadoneto, Nicola Conran, Joyce M Annichinobizzacchi, Sara Teresinha Olalla Saad, Fernando Ferreira Costa, Susan Kelly Picoli Quaino, Fabiola TrainaAbstract:Abstract 3227 Background: Sickle cell anemia (SCA) patients present an elevated rate of thrombotic complications and increased biological markers of hemostatic activation. Hemoglobin SC Disease (HbSC) is the second most prevalent Hemoglobinopathy after SCA (homozygous HbSS), has specific clinical and pathological characteristics that may differ from SCA, and viSCosity appears to be a hallmark of the Disease. Studies have shown an increase in thrombotic events in HbSC patients, especially pulmonary embolism, however, not much is known about the coagulation activation in this population. We herein aimed to evaluate the hypercoagulability markers in HbSC Disease and their associations with patients9 clinical and laboratory characteristics. Patients and Methods: This was a cross-sectional study performed on a cohort of 41 adult HbSC (mean age of 43 years) and 58 adult HbSS patients (mean age of 36 years), all in steady-state, and 25 healthy age-matched controls. We evaluated the expression of tissue factor (TF), the physiological initiator of coagulation, and thrombin-antithrombin complex (TAT), a final marker of coagulation activation. Leukocyte TF mRNA expression was analyzed by real time quantitative PCR and TAT plasma levels were measured by ELISA. Comparisons between the two patient groups and controls were performed using Kruskal-Wallis test followed by Dunn9s Multiple Comparisons test. Fisher9s exact test and Mann-Whitney9s U test were used to compare patients9 clinical complications and laboratory characteristics. Spearman9s rank test was used for correlations analysis. Results: Relative TF mRNA expression was significantly up-regulated in HbSC patients when compared to controls (2.6 vs. 1.2), however levels of TF were lower in HbSC than HbSS patients (2.6 vs. 3.3) ( P TF expression, TAT plasma levels were also higher in HbSC patients in comparison to controls (4.2 vs. 2.4), and lower in HbSC than HbSS patients (4.2 vs. 7.3); ( P P =0.001), monocyte (r=0.4; P =0.01), and platelet counts (r=0.5; P =0.002); and hemolysis markers: reticulocyte counts (r=0.4; P =0.01) and lactate dehydrogenase levels (r=0.6, P =0.0001). We also evaluated associations between TAT levels and clinical complications: stroke, pulmonary arterial hypertension, acute thoracic syndrome, retinopathy, osteonecrosis, leg ulcers, autosplenectomy and microalbuminuria. HbSC patients with retinopathy had significantly higher TAT levels (4.7 vs. 3.9; P =0.03) when compared with patients without this complication. TAT levels were also higher in patients with autosplenectomy (4.8 vs. 3.8; P =0.004), and in patients with osteonecrosis, although this had borderline statistical significance (4.6 vs. 3.9; P =0.06). TF expression significantly correlated with monocyte counts (r=0.6; P =0.01). Conclusions: Our results indicate that HbSC Disease patients present elevated coagulation activation markers when compared to controls, although not as intense as seen in SCA. Thrombotic complications in HbSC patients have been mainly linked to the hyperviSCosity present in this Disease. Our data suggest that inflammation and hemolysis are also important factors contributing to hemostatic activation, which may participate in the pathophysiology of very prevalent chronic complications of HbSC Disease: retinopathy and osteonecrosis. Interestingly, in our cohort, patients with autosplenectomy had higher levels of pro-coagulant markers, possibly due to a higher intravaSCular hemolytic rate and elevated peripheral blood counts. Although HbSC Disease is considered a milder form of SCA, autopsy studies have shown that mortality by pulmonary embolism is more frequent in HbSC Disease than in SCA, being the second cause of mortality in these patients (Manci et al, 2003). Studies addressing the pathophysiology of coagulation activation in HbSC Disease are lacking. Low numbers of cases of HbSC Disease are usually included in studies focusing mainly in SCA, and the results are very variable, probably due to the small numbers of patients. In view of the high prevalence and morbimortalilty of thrombotic complications in this population, we believe that future studies should focus on a better understanding of hypercoagulability in HbSC Disease. DiSClosures: No relevant conflicts of interest to declare.
Peter A Lane - One of the best experts on this subject based on the ideXlab platform.
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functional asplenia in Hemoglobin SC Disease
Blood, 1995Co-Authors: Peter A Lane, Zora R Rogers, Gerald M Woods, Jacquie L Oconnell, James Lear, Kathryn L Hassell, Doris L Wethers, Dennis W Luckey, George R BuchananAbstract:The incidence of functional asplenia in sickle-Hemoglobin C (SC) Disease has not been defined, and the use of prophylactic penicillin to prevent life-threatening septicemia in this disorder is controversial. The percentage of red blood cells with pits (pit count) is a reliable assay of splenic function in other disorders but has not been validated in Hemoglobin SC Disease. To address these issues, we conducted a prospective, multicenter study of splenic function in persons with Hemoglobin SC Disease. Baseline clinical data were recorded, and red blood cell pit counts were performed on 201 subjects, aged 6 months to 90 years, with Hemoglobin SC; 43 subjects underwent radionuclide liver-spleen SCanning. Pit counts greater than 20% were associated with functional asplenia as assessed by liver-spleen SCan, whereas pit counts less than 20% were found in subjects with preserved splenic function. Pit counts greater than 20% were present in 0 of 59 subjects (0%) less than 4 years of age, in 19 of 86 subjects (22%) 4 to 12 years of age, and in 25 of 56 subjects (45%) greater than 12 years of age. Other subjects with Hemoglobin SC, who had previously undergone surgical splenectomy, had higher pit counts (59.7% +/- 9.5%) than splenectomized subjects without Hemoglobinopathy (38.5% +/- 8.8%) or with sickle cell anemia (20.5% +/- 1.9%; P 20% in our laboratory) are higher than in other disorders. The routine administration of prophylactic penicillin to infants and young children with Hemoglobin SC Disease may not be necessary.
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fatal pneumococcal septicemia in Hemoglobin SC Disease
The Journal of Pediatrics, 1994Co-Authors: Peter A Lane, Winfred C. Wang, Zora R Rogers, Gerald M Woods, Judith A Wilimas, Scott T Miller, Yusuf Khakoo, George R BuchananAbstract:We retrospectively examined the medical and autopsy records of seven previously unpublished cases of fatal pneumococcal septicemia in children with Hemoglobin SC Disease. The earliest death occurred in a 1-year-old child who had congenital heart Disease with cyanosis; the other children were aged 31/2 to 15 years. Only one child had received pneumococcal vaccine or prophylactic penicillin therapy. All seven children had an acute febrile illness and rapid clinical deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in two patients were 40.3% and 41.7%, respectively (normal, ≤3.6%). Autopsy data from five cases showed marked splenic congestion without infarction in five, splenomegaly in four, and bilateral adrenal hemorrhage in three. These cases illustrate that functional asplenia predisposes some children with Hemoglobin SC Disease to the development of fatal septicemia after the age of 3 years. We conclude that pneumococcal vaccine should be administered to all children with Hemoglobin SC Disease and that acute febrile illnesses should be investigated promptly for the possibility of septicemia. The routine use of prophylactic penicillin therapy in infants and children with Hemoglobin SC Disease remains controversial.
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acute multiorgan failure syndrome a potentially catastrophic complication of severe sickle cell pain episodes
The American Journal of Medicine, 1994Co-Authors: Kathryn L Hassell, James R Eckman, Peter A LaneAbstract:Abstract The purpose of this report is to characterize the acute multiorgan failure syndrome that complicates some episodes of sickle pain. A retrospective chart review was used to identify episodes of sickle pain complicated by the acute failure of at least two of three organs: lung, liver, or kidney. The defining criteria of organ failure were established, and the clinical characteristics, laboratory values, treatment methods, and outcomes were noted in episodes that met the criteria. Seventeen episodes of acute multiorgan failure were identified in 14 patients, 10 with sickle cell anemia and 4 with Hemoglobin SC Disease. Most episodes occurred during a pain event that was unusually severe for the patient. The onset of organ failure was associated with fever, rapid fall in Hemoglobin level and platelet count, nonfocal encephalopathy, and rhabdomyolysis. Bacterial cultures were negative in all but four episodes. Aggressive transfusion therapy was associated with survival and with rapid recovery of organ function in all but one episode. The syndrome developed in patients who had previously exhibited relatively mild Disease with little evidence of chronic organ damage and relatively high Hemoglobin values in steady state. Acute multiorgan failure syndrome is a severe, life-threatening complication of pain episodes in patients with otherwise mild sickle cell Disease. The syndrome appears to be reversed with prompt, aggressive transfusion therapy. High baseline Hemoglobin levels may represent a predisposing factor.