scholarly journals Endothelial dysfunction and hypercoagulability in severe sickle cell acute chest syndrome

2021 ◽  
pp. 00496-2021
Author(s):  
Etienne-Marie Jutant ◽  
Guillaume Voiriot ◽  
Vincent Labbé ◽  
Laurent Savale ◽  
Hayat Mokrani ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Sickle Cell ◽  
Endothelial Activation ◽  
Community Acquired Pneumonia ◽  
Acute Chest Syndrome ◽  
Thoracic Pain ◽  
Coagulant Activity ◽  
Acute Pulmonary Hypertension ◽  
Fibrin Monomers

RationaleAcute pulmonary hypertension (PH) may develop during sickle-cell acute chest syndrome (ACS), and is associated with an increased mortality. Its mechanisms remain poorly known. The question was to assess if there is an endothelial dysfunction and a hypercoagulability in severe ACS, with and without acute PH.MethodsIn a prospective monocenter cohort follow-up study, all sickle-cell adult patients with ACS admitted to the intensive care unit underwent a trans-thoracic echography (TTE), and measurements of biomarkers of coagulation, endothelial activation, and platelet and erythrocyte activation. Acute PH was defined as a high echocardiographic probability of PH. The biological profiles of sickle-cell patients were analysed at the time of ACS, contrasting the existence of acute PH, and compared with steady state and with non-sickle-cell controls (healthy subjects and community-acquired pneumonia (CAP)).ResultsMost patients (36 patients with 39 ACS episodes; 23 males; 27 years old) had thoracic pain, dyspnea and CT scan lung consolidation. Acute PH was diagnosed in 7 patients (19%). Erythrocyte and platelet-derived microparticles (MPs) and the pro-coagulant activity of MPs were higher in ACS patients with acute PH, as compared with their counterparts. As compared with healthy controls, ACS patients had higher levels of tissue factor, fibrin monomers, D-dimer, release of pro-coagulant microparticles, and erythrocyte and platelet-derived MPs. As compared with CAP patients, ACS patients had increased levels of fibrin monomers, and erythrocyte and platelet-derived MPs.ConclusionsSevere ACS is characterised by endothelial dysfunction and hypercoagulability state, with a marked pro-coagulant profile in case of associated PH.

Asthma Is Associated with Acute Chest Syndrome, but Not an Increase Rate of Hospitalization for Pain among Children with Sickle Cell Anemia: A Retrospective Cohort Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3406-3406
Author(s):  
Francoise Bernaudin ◽  
Robert C. Strunk ◽  
Annie Kamdem ◽  
Cecile Arnaud ◽  
Ping An ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Therapeutic Intervention ◽  
Retrospective Cohort ◽  
Inhaled Corticosteroids ◽  
Medical Center ◽  
Acute Chest Syndrome ◽  
Thoracic Pain ◽  
Transfusion Therapy

Abstract Introduction In this study, we sought to validate the previous findings that asthma increases the incidence of acute chest syndrome (ACS) and pain in children with sickle cell anemia (SCA). Methods A retrospective cohort was comprised of children with SCA evaluated for at least six months from a single medical center. Asthma was defined as being present when the first wheezing episode was heard by a physician after the age of 2 years or after 3 episodes of bronchiolitis before the age of 2 years. ACS was defined as a recent abnormal X-ray of the lungs associated with fever, respiratory signs or thoracic pain. A painful episode was defined as pain that resulted in hospitalization. Therapeutic intervention (hydroxyurea, blood transfusion therapy or transplant) was uniformly applied to all children with three or more episodes of pain that required hospitalization within a 12 month period. Patient years were accumulated from birth until death, lost to follow up, last visit to the center or a therapeutic intervention, whichever came first. Results A total of 297 children with SCA were evaluable for a doctor diagnosis of asthma for a total of 1,805 patient-years. The mean length of follow-up was 6.1 patient-years. A doctor diagnosis of asthma was present in 8.4% (25 of 297). Among the children with asthma 75% (19 of 25) were consistently prescribed a beta 2 agonist or inhaled corticosteroids. After adjustment for the effect of age, asthma was significantly associated with ACS event (p = 0.03) but pain was not (>0.05). Conclusion Among children with SCA, asthma is associated with an increased incidence of ACS, but not pain that required hositalization. The absence of an association between asthma and pain may be related to uniform therapeutic intervention for children with repetitive painful episodes that require hospitalizations coupled with active treatment for asthma in most of the children.

Treatment with Hydroxyurea in Sickle Cell/ ß Thalassemia: A Long-Term Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1678-1678 ◽  
Author(s):  
Aurelio Maggio ◽  
Paolo Rigano ◽  
Disma Renda
Keyword(s):  
Sickle Cell ◽  
Brain Mri ◽  
Heavy Smoker ◽  
Acute Chest Syndrome ◽  
Common Disease ◽  
Long Term Treatment ◽  
Sickle Cell Crises ◽  
New Onset

Abstract Sickle cell/ß-Thalassemia is a common disease in areas where ß-Thal and ßS genes are endemic, like in Sicily. In the current study we evaluated clinical and hematological data of Sicilian patients with Sickle cell/ß-Thalassemia treated with Hydroxyurea (HU). The endpoint of the study was to evaluate the efficacy of HU in terms of reduction of sickle cell crises after 2 years of treatment in comparison with the 2 years before. Moreover, we evaluated the outcome after long-term treatment. Fortytwo patients (18 males, mean age 36, range 18–53) were treated with HU (mean dosage 15 mg/kg, range 10–30) for an average 6.6 years follow-up (range 3–9 years). Twentytwo were ß0/ßS and 20 ß+/ßS genotype. All had 3 or more crises in the year before starting HU. We observed a significant reduction in sickle cell crises (7.8 ± 6.9 crises per year versus 0.9 ± 1.8 per year, P < 0.0001), hospitalizations (2.5 ± 2.9 per year versus 0.3 ± 1.5, P < 0.0001), and days in hospital (22.4 ± 21.9 per year versus 1.2 ± 2.3, P < 0.0001). Altogether, there was a 86% reduction in vasoocclusive events in comparison with the 2 years before (P < 0.001). Moreover, there was a significant increase of MCV (71.4 versus 97.5fl, P < 0.0001), HbF (7.5 versus 25.2 %, P < 0.0001), and decrease of WBC (11.4 versus 9.2 109/L P < 0.01) and reticulocytes (14.1 versus 10.2%, P< 0.01). Finally, redution of hyperdense cells and increase of erithropoyetin were seen. After a mean follow-up of 6.6 years, 39 patients are alive. Three died (2 end stage HCV related liver disesases, 1 bleeding after ERCP). Nine of the 40 alive patients developed complications: 1 acute chest syndrome, 2 strokes, 2 myocardial infarctions, 4 bone necrosis. Brain MRI of 15 patients after and during a mean of 6.9 years of HU treatment showed 2 new onset strokes, 1 of which in a patient with a previous stroke. Moreover, 4 patients developed new onset asymptomatic ischemic brain lesions. In every case there had been a significant reduction of sickle cell crises. There were two cases of cancer, occurring in two patients who were brother and sister: lung cancer in the former, a proeviously heavy smoker, breast cancer in the latter. No further serious adverse events were seen. Five patients with iron overload were treated with Deferiprone: no drug interaction with HU was noticed. Our study confirms that HU is effective in reducing clinical relevant crises of patients with Sickle cell/ß-Thalassemia. However, our preliminary data suggest that chronic organ damages are not prevented by HU. Safety has to be assessed by more prolonged studies.

Stroke in Sickle Cell Anemia After Excellent Response to Hydroxyurea.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4622-4622
Author(s):  
Ubaldo Martinez ◽  
Samir K. Ballas
Keyword(s):  
Atrial Septal Defect ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Septal Defect ◽  
Acute Chest Syndrome ◽  
Excellent Response ◽  
Blood Exchange ◽  
Atrial Shunt ◽  
The Right

Abstract Abstract 4622 Introduction Strokes occur in about 10% of children with sickle cell anemia (SS) less than 10 years old. These strokes are usually ischemic in nature. Stroke due to SS in adults is less common and is usually hemorrhagic in nature. We wish to report an unusual adult patient with SS and excellent response to HU who developed a stroke that was unrelated to SS. Case Report and Results A 35-year-old female with sickle cell anemia had mitral valve prolapse and migraine headaches presented 2 days after developing abrupt bilateral blurry vision, left facial numbness and weakness of her left leg. Her SS has been complicated by acute chest syndrome, bilateral hip avascular necrosis and frequent painful crises prior to hydroxyurea (HU) therapy. She was enrolled in the multicenter study of hydroxyurea (MSH) in SS and has been on 2500mg of HU per day for the past 13 years. She had an excellent response to HU with no recurrent acute chest syndrome and decreased need for blood transfusion. After starting HU, the frequency of crises requiring hospital admission decreased from 1 admission every 1 to 2 months to less than 1 admission per year except when hydroxyurea was discontinued for pregnancy. Her fetal hemoglobin increased from 6.1 % before HU to a maximum of 45%. Her MCV increased from 96 fl to a maximum of 132 fl and Hb from 8.0 g/dl to 9.8 g/dl Her exam was remarkable for left lower extremity weakness which was more pronounced proximally. All cranial nerves were intact and there was normal sensation bilaterally. CT scan of the brain showed three foci of hypodensity and MRI of the brain showed increased signal on T2, FLAIR and diffusion weighted images within the frontoparietal deep white matter consistent with infarction in the border zone of the middle cerebral artery (MCA)-anterior cerebral artery (ACA). MR angiography of the intracerebral and extracerebral vessels demonstrated focal narrowing of the right MCA at the trifurcation suggesting an embolic cause. Common causes of stroke were ruled out with routine studies. Her hemoglobin electrophoresis after admission but before blood exchange transfusion showed HbS of 55% and HbF of 45%. She underwent exchange transfusion 2 days after admission and was started on chronic blood exchange transfusions with the assumption that she had ischemic stroke due to SS. Initial transthoracic echocardiogram with contrast injection did not show an atrial shunt. Follow-up transesophageal echocardiogram after discharge showed a secundum atrial septal defect with a defect size of 1.4 cm. Right heart catheterization was performed and the pulmonary flow to systemic flow (Qp/Qs) was 1.7:1. An Amplatzer atrial septal defect (ASD) closure device was deployed with transesophageal echocardiographic guidance and a large thrombus was removed from the right atrium. At the patient's request exchange red cell transfusions were discontinued. The patient has continued treatment with hydroxyurea and aspirin. Conclusions Young patients with cryptogenic stroke have a much higher prevalence of atrial shunts and in particular patent foramen ovale than patients with other forms of stroke and therefore a cause-effect association is suggested. Young adults with stroke should be evaluated for common and reversible causes of stroke including paroxysmal emboli. Transesophageal echocardiography is the gold standard for diagnosing atrial shunts. Strokes in patients younger than age 55 are related to paroxysmal emboli and have a risk of recurrence of approximately 30% within one year. High risk features for stroke recurrence with an atrial shunt include hypercoagulable states, large opening and presence of an atrial septal aneurysm. Optimal management of patients with a stroke and an atrial shunt is unknown. Options include surgical closure, percutaneous device closure, anticoagulation and antiplatelet therapy. Patients with sickle cell disease and stroke should receive long term blood transfusions to reduce HbS below 30% if the stroke is felt to be related to sickle cell disease vasculopathy. The patient described with SS had a stroke and had an atrial septal defect that was repaired. The MRI/MRA findings are consistent with paroxysmal emboli. The patient is receiving treatment with hydroxyurea and aspirin having discontinued red cell exchange transfusions and at two years of follow-up has not had a recurrent stroke. Disclosures: No relevant conflicts of interest to declare.

Serum Transferrin: An Independent Predictor of Mortality in Sickle Cell Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2126-2126
Author(s):  
Zahra Pakbaz ◽  
Mariana E Hildesheim ◽  
Shoaib Alam ◽  
Darlene Allen ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Independent Predictor ◽  
Stable Condition ◽  
Acute Chest Syndrome ◽  
Serum Transferrin ◽  
Significant Difference

Abstract Abstract 2126 Introduction: Serum ferritin (SF), the most convenient marker of iron burden in sickle cell anemia (SCA), is potentially confounded by effects of inflammation in SCA. Serum transferrin (STF) has been described as one of the independent predictors of elevated tricuspid regurgitant velocity (TRV) in SCA. Therefore in this report we investigate the potential predictive role of STF in morbidity and mortality of individuals with SCA. Methods: Patients with sickle cell disease documented by high-pressure liquid chromatography were eligible for the study. Four hundred and sixty SCA patients were recruited in this study from the community through multimedia advertisements, community outreach, and regional clinics. All evaluated patients were screened by history taking, physical examination, laboratory studies, and transthoracic echocardiography. All patients provided written informed consent. The advertisements and protocol were approved by the institutional review boards of the National Heart, Lung, and Blood Institute and Howard University. Only outpatients in stable condition were included; patients who had had a vaso-occlusive crisis within the previous two weeks or an episode of acute chest syndrome within the previous four weeks were excluded. Results: Two hundred and sixty two participants with HbSS were included in the data analysis. Forty-seven percent were male. Median age was 32 years old. Median TRV in this cohort was 2.4 m/s. Forty nine percent of participants had TRV≥2.5 m/s and 19% had TRV≥3 m/s. Patients with lower STF (<164 mg/dl) were older (p=0.01), had more blood transfusions in the past (p<0.0001) and did not have more complications of sickle disease (priapism, acute chest syndrome, leg ulcers or emergency room visits, all p>0.05), but all-cause death rate was higher (22% vs. 6%, p=0.0001). Hemoglobin, CRP, alkaline phosphatase, uric acid, placenta growth factor (<0.001), SF and iron saturation were found to be higher and kidney function was worse. Patients with lower STF level were also more likely to have TRV≥3.0 m/s (32% vs. 13%, p<0. 001) but there was no significant difference in BNP and ejection fraction. Patients with lower STF had endothelial dysfunction, as indicated by a blunted forearm blood flow (FBF) response to infusion of acetylcholine into the brachial artery (p<0.01). Among age, gender, BNP, TRV,GFR,WBC, STF, systolic blood pressure and fetal hemoglobin, the Cox proportional analysis of mortality found TRV, GFR and STF the independent significant predictors of mortality in this cohort. Kaplan-Meier survival curve showed that patients with transferrin <164 mg/dl had significantly lower survival (p<0.001). Conclusion: In this cohort of adults with sickle cells anemia, STF is found to be an independent predictor of endothelial dysfunction, high TRV and mortality. It may be a more sensitive predictor than serum ferritin. We propose that iron overload may induce a state of endothelial dysfunction that is a risk factor for clinical vasculopathy and death. Disclosures: No relevant conflicts of interest to declare.

A North American Experience Of Hemoglobin SC Disease, Its Complications, and Management

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2221-2221 ◽  
Author(s):  
Veronique Naessens ◽  
Richard Ward ◽  
Kevin H.M. Kuo
Keyword(s):  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Care Center ◽  
Comprehensive Care ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Baseline Hemoglobin ◽  
Hemoglobin Sc Disease

Background The phenotype of hemoglobin SC (HbSC) disease is distinct from sickle cell anemia (SCA) (HbSS and S/b0) but management of adults is mostly derived from studies of the latter group. Longitudinal observational studies on the complications and outcomes of hemoglobin SC disease are largely confined to centers outside North America. The unique ethnic composition of our cohort, consisting of mostly Western Africans and West Indians, permits further characterization of the HbSC phenotype. Objective to describe the baseline characteristics and long-term complications of a cohort of adult HbSC patients followed in a Canadian sickle cell comprehensive care center. Methods A retrospective observational cohort study was conducted on all adult patients with HbSC disease attending a sickle cell comprehensive care center in Toronto, Canada from 1994 to 2013. Baseline demographics, acute and chronic complications attributable to sickle cell disease, and laboratory data were collected. Medians were used to describe continuous variables, while percentages or ratios for categorical variables. Logistic regression was used to examine factors influencing the main clinical complications. Results 104 patients were included in the analysis, comprising of 38.5% males and 61.5% females. Median length of follow-up was 3.5 years (1 - 19) and median age at last recorded visit was 35 years (18 - 68). Median baseline hemoglobin was 119 g/L (82 - 153 g/L), hematocrit 0.340 (0.250 - 0.440), and fetal hemoglobin (HbF) fraction 1% (0 - 7.7%). Most frequent complications encountered were retinopathy (55.8%) and symptomatic avascular necrosis (27.9%), followed by painful vaso-occlusive crises requiring emergency room visit (23.1%). Presence of retinopathy was associated with higher baseline hemoglobin (OR 2.72 for every 10 g/L of hemoglobin, p = 0.037) and older age (OR 2.72 for every decade, p < 0.001). Acute chest syndrome (7.7%), priapism (7.5% of men), and renal involvement (8.2%), were less common than reported in the literature, while the rates of venous thromboembolism (8.7%), symptomatic infarctive or hemorrhagic stroke (2.9%) were slightly more common. Median right ventricular systolic pressure on 2D-transthoracic echocardiogram was 29 mmHg (17 – 43 mmHg). No patient underwent a right heart catheterization. Two patients died from septic shock, both at the age of 29. Disease-modifying therapy most often consisted of hydroxyurea (28.8%), followed by exchange transfusion (6.7%) and phlebotomies (5.8%). Hydroxyurea significantly increased the median HbF fraction (from 1% to 2.75%, p = 0.004 by related-samples Wilcoxon signed rank test). Conclusion In this large North American cohort of adult patients, we have again shown that HbSC disease is not as benign as traditionally thought. As such, patients with HbSC disease warrant similar follow-up to that provided to SCA. Retinopathy, avascular necrosis and painful vaso-occlusive crises were the most common complications in our study, albeit lower than in other reported cohorts. The frequent use of hydroxyurea in this cohort is quite unique compared to other sickle cell comprehensive care centers reported in the literature. However, therapeutic phlebotomy is less often used compared to the European experience. We also observed a lower frequency of retinopathy, avascular necrosis, painful vaso-occlusive crises, priapism and acute chest syndrome. Whether this observation is due to hydroxyurea use or to other genetic or environmental factors remains to be determined. Further studies are also required to develop a more evidence-based therapeutic strategy for this genotype of Sickle Cell Disease. Disclosures: No relevant conflicts of interest to declare.

Incidence and Risk of Delayed Hemolytic Transfusion Reaction in Sickle Cell Disease Patients Based on a Prospective Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 95-95 ◽  
Author(s):  
France Pirenne ◽  
David Narbey ◽  
Philippe Chadebech ◽  
Armand Mekontso-Dessap ◽  
Pablo Bartolucci ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Prospective Study ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Hemolytic Transfusion Reaction ◽  
Delayed Hemolytic Transfusion Reaction ◽  
Prospective Longitudinal

Abstract Background Delayed hemolytic transfusion reaction (DHTR) is a life threatening complication of transfusion in sickle cell disease (SCD). This syndrome is underestimated because of a clinical picture that resembles a vaso-occlusive crisis (VOC) and the frequent absence of detectable antibodies. Several retrospective studies have evaluated the frequency of DHTR based on case reports. We conducted a prospective, longitudinal, single center study to determine the incidence of DHTR and the risk of developing DHTR depending on the transfusion regimen: chronic versus punctual. Methods and patients SCD patients aged over 18 years, undergoing a transfusion, were enrolled in this study. A total of 697 transfusion episodes (TE) in 312 patients were included during 30 months. Some patients had multiple TE during the period. The post transfusion outcome of the patients was assessed up to one month after the included TE. DHTR was confirmed based on the rapid disappearance of HbA (> 50% 15 days post-transfusion) associated with two of the following criteria up to three weeks after transfusion: VOC symptoms, dark urine, worsening anemia, increased LDH. Transfusion episodes were divided into chronic (336 TE in 111 patients) and punctual (361 TE in 201 patients). Chronic transfusions were defined as regular transfusions to treat chronic complications or for primary/secondary prevention of complications. Short transfusion program during pregnancy was considered as punctual transfusions if patients were not previously regularly transfused. The study obtained approval of the local Ethics Committee. Results Follow-up of the patients after transfusion showed 15 DHTR during the study. They all developed in punctually transfused patients. Thus, patients who are transfused punctually have a significantly higher risk of developing DHTR than those in a regular transfusion program (p < 0.001). When considering only punctual transfusions, the incidence of DHTR is 4.2% per transfusion episode (IC 95% [2.6; 6.9]) and 7.5% per patient during the 30 months of the study (IC 95% [4.6; 12.4]). In these DHTR cases, the transfusion indication was surgery (n = 6), pregnancy (n = 3), acute chest syndrome (n = 3), stroke (n = 1), profound anemia (n = 1), and VOC prevention before a school exam (n = 1 case). Two patients died of multi-organ failure following severe intravascular hemolysis. The median hemoglobin decrease for all DHTR cases after the triggering transfusion was 4.4 g/dl [IQR 3.6-5.2]; the highest LDH level was 879 [IQR 680-1423]. Ten patients developed newly formed antibodies, but only five among them displayed antibodies with significant serological features (anti-Fya, anti-S, anti-Jka, anti-HI). In the five other cases, the antibodies were of unspecified specificity or auto antibodies in the RH blood group (the genetic RH background was known). Finally, antibodies were undetectable for five cases, confirmed by long-term patient follow up. Conclusion This prospective study demonstrates, for the first time, that DHTR is a frequent reaction in adult SCD patients, developing only in occasionally transfused patients. This finding highlights that adult patients with regular transfusion who did not previously encountered DHTR are not susceptible to developing this severe reaction. A mechanism linked to acute situations can be suggested as already shown for the induction of allo-immunization. However, many cases developed without detectable antibodies, confirming the complex pathophysiology of this syndrome. A bio-clinical scoring system to predict DHTR, based on this study, is under development and will be presented. Disclosures Michel: Roche: Research Funding.

Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3628-3632 ◽  
Author(s):  
Alina Ferster ◽  
Parvine Tahriri ◽  
Christiane Vermylen ◽  
Geneviève Sturbois ◽  
Francis Corazza ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Significant Difference ◽  
History Of ◽  
Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P &lt; .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS)

Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2354-2363 ◽  
Author(s):  
Ersi Voskaridou ◽  
Dimitrios Christoulas ◽  
Antonios Bilalis ◽  
Eleni Plata ◽  
Konstantinos Varvagiannis ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Hospital Admissions ◽  
Fetal Hemoglobin ◽  
Acute Chest Syndrome ◽  
Prolonged Administration ◽  
Probability Of Survival ◽  
Transfusion Requirements ◽  
History Of

The aim of this prospective study was to evaluate the long-term efficacy and safety of hydroxyurea (HU) in patients with sickle cell disease (SCD). Thirty-four patients with sickle cell anemia (hemoglobin S [HbS]/HbS), 131 with HbS/β0-thal, and 165 with HbS/β+-thal participated in this trial. HU was administered to 131 patients, whereas 199 patients were conventionally treated. The median follow-up period was 8 years for HU patients and 5 years for non-HU patients. HU produced a dramatic reduction in the frequency of severe painful crises, transfusion requirements, hospital admissions, and incidence of acute chest syndrome. The probability of 10-year survival was 86% and 65% for HU and non-HU patients, respectively (P = .001), although HU patients had more severe forms of SCD. The 10-year probability of survival for HbS/HbS, HbS/β 0-thal, and HbS/IVSI-110 patients was 100%, 87%, and 82%, respectively, for HU patients and 10%, 54%, and 66%, for non-HU patients. The multivariate analysis showed that fetal hemoglobin values at baseline and percentage change of lactate dehydrogenase between baseline and 6 months were independently predicted for survival in the HU group. These results highlight the beneficial effect of HU, which seems to modify the natural history of SCD and raise the issue of expanding its use in all SCD patients.

Progression of Pulmonary Hypertension in Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3187-3187 ◽  
Author(s):  
Kenneth I. Ataga ◽  
Charity Moore ◽  
Susan Jones ◽  
Oludamilola Olajide ◽  
Dell Strayhorn ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Right Atrial ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Original Cohort ◽  
The Mean

Abstract Introduction: The prevalence of pulmonary hypertension (PHT) is high in patients with sickle cell disease (SCD). Although most patients have only mild increases in their pulmonary artery systolic pressure (PASP), the presence of PHT is strongly associated with an increased risk of death. While PHT seen in SCD is thought to progress over time, both the rate of development of PHT and the factors that affect disease progression remain unknown. Methods: The 41 subjects in this study were drawn from an original cohort of 60 patients followed in the Sickle Cell Clinic at UNC-Chapel Hill. All patients were previously evaluated for PHT (defined using an age-, sex-, and BMI-adjusted reference range). Of the 60 patients in the original cohort, six are now deceased and 13 others were not available for repeat evaluation. The PASP was determined using Doppler echocardiography and then applying the modified Bernoulli equation (PASP = 4V2 + right atrial pressure). Individuals were not studied if they: 1) showed clinical evidence of left ventricular failure; 2) had a recent acute illness (e.g., vaso-occlusive crisis); or 3) had experienced an episode of acute chest syndrome within the preceding 4 weeks. Means and standard deviations were calculated for all measures at the time of initial evaluation and at the time of follow-up. Results: Of the 41 subjects in our study, PHT was originally present in 12, while no evidence of PHT was present in 29. Of the 29 subjects who initially had no evidence of PHT, 4 (or 14%) have now developed PHT (mean follow-up period of 3.3 ± 0.4 years). In these 4 subjects, the mean PASP at the time of initial and follow-up evaluations respectively were: 37.0 ± 2.0 mm Hg vs. 55.8 ± 11.0 mm Hg. The patients who developed PHT during the course of the study had lower systolic BP (143 ± 12 mm Hg vs. 128 ± 12 mm Hg), lower fetal hemoglobin levels (6.2 ± 5.7 % vs. 4.2 ± 3.7 %), and higher platelet counts (276 ± 119 X 103/μL vs. 426 ± 96 X 103/μL) at the time of their follow-up analyses. By contrast, 3 of the 12 subjects (or 25%) who were thought to have PHT at the time of their original evaluations were found to have normal PASP determinations at the time of their repeat echocardiograms (mean follow-up period of 3.2 ± 0.6 years). In these latter 3 subjects, the mean PASP values at the time of the initial and follow-up evaluations respectively were: 40.0 ± 4.6 mm Hg vs. 33.7 ± 4.7 mm Hg. Conclusion: In this small group of patients with SCD, we found that PHT developed in 14% of subjects who had no evidence of PHT 3 years earlier. Based on this observation, it seems that periodic echocardiograms to screen for the development of PHT would be appropriate. On the other hand, our observation that some patients initially classified as having PHT failed to have elevated PASP measurements at the time of follow-up illustrates the limitation of a single echocardiographic evaluation in establishing this diagnosis. Because of the increase in PASP that occurs during acute vaso-occlusive episodes, and the difficulty usually encountered in distinguishing steady state from crisis, the initial elevation of the PASP in these patients could have resulted from sub-clinical crisis states. For these reasons, a patient found to have an elevated PASP at the time of a screening echocardiogram should have a repeat study, and perhaps a right heart catheterization, before the diagnosis of PHT is firmly established.

The Eveluation of Pulmonary Functions in Children with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4628-4628
Author(s):  
Cem Kurt ◽  
Ilgen Sasmaz ◽  
Bulent Antmen ◽  
Yurdanur Kilinc ◽  
Sadi Kurdak ◽  
...  
Keyword(s):  
Patient Group ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Exercise Test ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Healthy Children ◽  
Diffusion Test ◽  
Pulmonary Functions

Abstract Abstract 4628 Aim In this study we evaluated to pulmonary functions and determined relations of these findings with clinical parameters in children with sickle cell anemia (SCA) who were at follow up in our pediatric heamatology clinic. Materials and Methods 24 children with sickle cell anemia and 9 healthy children as control group include to the study. Complete blood count, hemoglobin electrophoresis and biochemical values were eveluated for both groups. At pulmonology department, the carbonmonoxide diffusion test performing for both groups. At the same day spirometric respiratory function evaluation and exercise test performed both groups at department of sports physiology. The data recieved are compared statistics. Results HbS, HbF, SGPT, ferritin, total bilirubine, direkt bilirubine and Fe++ values were high at patient group (p<0.05). Hemoglobin and hematocrit values were low at patient group according to control group as expected (p<0.05). The number of SCA patient who had one-three venoocclusive crises (VOC) were 14 (58.3%), patient who had three or more VOC were 7 (29.2%) and patient who had no VOC were 3 (12.5%). The number of patient who had acute chest syndrome (ACS) were 5 (20.9%) and 19 patients had no ACS (79.1%). Ýmpaired isole carbonmonoxide diffusion test was established at the 62.5% of the patient's. At patient group, spirometric FEV1 and MEF25 measurement were found lower than the control group (p<0.05). At exercise test VO2/HR rate were lower for patient group (p<0.05). VE/VO2 rate (p=0.023) and R (p=0.016) measurement were found higher. Conclusion Pulmonary gas transfer was found difficult in patients with SCA. Respiratory airways established obstructed in spirometric evaluation. Obstructive defficiensies have to be follow up. Oxygen pulse and respiratory exchange rates were determined low and more oxygen usage was observed for aerobic metabolic activity. With these results, ýt can be say that chronic inflamation process at lung due to oxygen radicals and hipoksemia in sickle cell patients, the aerobic respiratory load was increased. Disclosures: No relevant conflicts of interest to declare.

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