Abnormal Pulmonary Function in Adults and Children with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2319-2319 ◽  
Author(s):  
Claudia R. Morris ◽  
Jennifer Gardner ◽  
Andrew Wen ◽  
Shanda Robertson ◽  
Ward Hagar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Lung Function ◽  
Pulmonary Function ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Asthma Treatment ◽  
Cell Disease ◽  
History Of ◽  
Adults And Children

Abstract Introduction: Chronic lung disease is a fatal complication in sickle cell disease (SCD) often undiagnosed until late stages. Early detection and treatment of risk factors may improve survival. Since asthma, pulmonary hypertension (PHT), and acute chest syndrome (ACS) are potential risk factors, in 1998, we began screening patients with history of ACS or wheezing with pulmonary function tests (PFT) and echocardiogram (echo). Methods: A chart review was completed on the 362 adults and children evaluating history of asthma, lung function (PFT) and PHT (echo, tricuspid regurgitant jet velocity ≥ 2.5). Results: PFT Findings All Ages Adults Children PHT (All Ages) Study performed 34% (124/362) 41% (95/232) 22% (29/130) Echo: 90% (111/124) Abnormal 85% (106/124) 87% (83/95) 79% (23/29) 51% (54/106) Obstructive (OBS) only 31% (33/106) 31% (26/83) 30% (7/23) 42% (14/33) Restrictive (REST) only 30% (32/106) 28% (23/83) 39%(9/23) 38% (12/32) Both OBS + REST pattern 27% (29/106) 29% (24/83) 22% (5/23) 69% (20/29) “Abnormal,” not specified 11% (12/106) 12% (10/83) 9% (2/23) 67% (8/12) DLCO < 65% predicted 48% (45/94) 53% (42/80) 21% (3/14) 54% (26/48) Diagnosis & Treatment Clinical asthma diagnosis 13% (47/362) 14% (33/232) 11% (14/130) 43% (20/47) Receiving asthma treatment 51% (24/47) 45% (15/33) 64% (9/14) 50% (12/24) Bronchodilator only 23% (11/47) 24% (8/33) 21% (3/14) 45% (5/11) Inhaled steroid 23% (11/47) 18% (6/33) 36% (5/14) 55% (6/11) Singulair 4% (2/47) 3% (1/33) 7% (1/14) 50% (1/2) PFT suggests asthma 50% (62/124) 53% (50/95) 41% (12/29) 53% (33/62) +PFT, + asthma treatment 16% (10/62) 14% (7/50) 25% (3/12) 80% (8/10) One hundred twenty-four patients underwent PFTs, of which 111 (85%) were abnormal. Obstructive and/or restrictive disease with abnormal diffusion capacity were widespread. Of patients with an obstructive pattern, only 16% were receiving any asthma treatment. Forty-seven patients (33 adults and 14 children) were diagnosed with asthma. However, only half were receiving any treatment: 23% bronchodilators, and 23% inhaled steroids. Echo was performed on 90% of patients with PFT data. Half of all patients with abnormal PFTs, and 69% of those with obstructive/restrictive patterns, had PHT. Conclusion: While a more severe population may have been tested, this data suggests abnormal lung function is prevalent in SCD and is associated with PHT. Recent data suggests abnormal NO metabolism may link asthma and PHT in SCD. In conclusion, our data suggests patient morbidity will be decreased by regular screening with PFT and echo followed by early treatment for asthma and PHT.

scholarly journals Risk Factors for Adverse Maternal and Fetal Outcomes in Pregnant Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3117-3117
Author(s):  
Sherraine Della-Moretta ◽  
William Marshall ◽  
Rui Li ◽  
Erin Cleary ◽  
Philip Samuels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Maternal Age ◽  
Acute Chest Syndrome ◽  
Hypertensive Disorders Of Pregnancy ◽  
Cell Disease ◽  
History Of ◽  
Maternal Bmi

Abstract Background Approximately 100,000 Americans are affected by sickle cell disease (SCD), an inherited hematologic disorder. In women with sickle cell disease, pregnancy is associated with increased maternal and fetal adverse outcomes (Elenga et al). However, there is a paucity of data on risk factors for adverse events in this population. This retrospective study seeks to add to the deficient repertoire of information regarding maternal and fetal outcomes in patients with sickle cell disease and their children. Methods We retrospectively evaluated pregnancy outcomes of women with SCD who had previously undergone echocardiography from the year 2000-2021. The associations between clinical variables and adverse hematologic (AHE), cardiac (ACE), obstetric (AOE) and fetal/neonatal (ANE) events were evaluated by the Generalized Linear Model (GLM). The adverse hematologic events were vaso-occlusive crisis (VOC) antepartum and postpartum, acute chest syndrome, venous thromboembolism antepartum and postpartum, and transfusion antepartum. Results We identified 43 women/59 pregnancies with a median maternal age 27 years old (interquartile range [IQR] 20), pre-pregnancy BMI 25 kg/m2 (IQR 16). Maternal sickle cell genotype was SS in 31 (72%) women/37 (63%) pregnancies, SC in 8 (18%) women/18 (31%) pregnancies, and other genotype in 4 (9%) women/4 (7%) pregnancies. Prior venous thromboembolism was present in 12 (27%) women/15 (25%) pregnancies and prior acute chest syndrome (ACS) in 33 (80%) women/41 (75%) pregnancies. In the year before pregnancy, 24 (56%) women were admitted at least once for VOC. There were no maternal deaths during pregnancy or up to 1 year postpartum. AHE (n = 171) occurred in 43 (73%) pregnancies (Figure A), with a median of 2 (range 0-13) AHE per pregnancy. AHE were more common with genotype SS, history of ACS, history of ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, tricuspid regurgitation velocity (TRV) >2.5 m/s on echocardiogram, and increased maternal age, and less common with increased hemoglobin (Figure B). ACE were rare (n = 3) (Figure A) and weakly associated with increased maternal age (Figure C). AOE (n = 37) occurred in 27 (45%) pregnancies (Figure A) and were associated with lower pre-pregnancy maternal BMI (Figure D). ANE (n = 54) occurred in 27 (46%) of pregnancies, and were associated with maternal hypertensive disorders of pregnancy (Figure E). Conclusions We found that AHE during pregnancy in women with SCD were associated with genotype SS, history of ACS, ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, higher maternal age, and inversely related to hemoglobin. In addition, AHE during pregnancy were associated with TRV >2.5 m/s on echocardiogram, which has not been previously shown in women with SCD. These data may be useful to identify women at increased risk during pregnancy. Data show that patients with sickle cell disease who have more disease-related complications including history of acute chest syndrome, frequent pain crisis, elevated TRV on echocardiogram, and lower hemoglobin are at greater risk for AHE. This suggests that disease severity is directly related to outcomes. The association between increased maternal age and ACE has been demonstrated in the past in women without SCD (DeViti et al). The same can be noted for the association of AOE with lower maternal BMI (Verma et al), and ANE being associated with maternal hypertensive disorders of pregnancy (Lugobe et al). In the future, prevention of these complications will be key. Future directions include determining the effect of disease-modifying therapy on these outcomes, though safety during pregnancy has not yet been demonstrated for more novel agents such as voxelotor and crizanlizumab. With more information on these risk factors, we hope that modification and treatment can result in better outcomes. Figure 1 Figure 1. Disclosures Desai: Pfizer: Other: Publication Fee, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding.

scholarly journals To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

2021 ◽  
pp. 1-5
Author(s):  
Justin E. Juskewitch ◽  
Craig D. Tauscher ◽  
Sheila K. Moldenhauer ◽  
Jennifer E. Schieber ◽  
Eapen K. Jacob ◽  
...  
Keyword(s):  
Pregnant Woman ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pregnancy Termination ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Childbearing Age ◽  
Procedural Complications ◽  
History Of ◽  
Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

scholarly journals Alkaline Phosphatase Is Associated with Red Cell Alloimmunization in the Pulmonary Hypertension and Hypoxic Response (PUSH) Sickle Cell Disease Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Victoria Brooks ◽  
Oluwalonimi Adebowale ◽  
Victor R. Gordeuk ◽  
Sergei Nekhai ◽  
James G. Taylor
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Severe Disease ◽  
Case Control ◽  
Red Cell ◽  
Cell Disease ◽  
History Of

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with >10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.

scholarly journals Pulmonary function in sickle cell disease with or without acute chest syndrome

1998 ◽  
Vol 12 (5) ◽  
pp. 1124-1129 ◽  
Author(s):  
F. Santoli ◽  
F. Zerah ◽  
N. Vasile ◽  
D. Bachir ◽  
F. Galacteros ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Function ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Cell Disease

Low‐risk factors for severe bacterial infection and acute chest syndrome in children with sickle cell disease

2019 ◽  
Vol 66 (6) ◽  
pp. e27667 ◽  
Author(s):  
Elena María Rincón‐López ◽  
María Luisa Navarro Gómez ◽  
Teresa Hernández‐Sampelayo Matos ◽  
Jesús Saavedra‐Lozano ◽  
Yurena Aguilar de la Red ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Bacterial Infection ◽  
Sickle Cell ◽  
Low Risk ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Severe Bacterial Infection

Pulmonary Hypertension in Sickle Cell Disease: A Common Complication for Both Adults and Children.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1666-1666 ◽  
Author(s):  
Claudia R. Morris ◽  
Jennifer Gardner ◽  
Ward Hagar ◽  
Elliott P. Vichinsky
Keyword(s):  
Pulmonary Hypertension ◽  
Liver Disease ◽  
Sickle Cell Disease ◽  
Renal Disease ◽  
Sickle Cell ◽  
Significant Risk ◽  
Common Complication ◽  
Cell Disease ◽  
History Of ◽  
Adults And Children

Abstract Pulmonary hypertension (PHT) is a risk factor for death in adults with sickle cell disease (SCD). Although occurring in >30% of adult patients, routine screening is not yet standard of care, and many patients are undiagnosed and untreated. Little is known on the prevalence of PHT in the pediatric population. A retrospective chart review was performed on 362 patients to evaluate screening practices and prevalence of PHT in both adults and children with SCD. Thirty percent (n=110) were < 18 years old, and gender was equally distributed. This review identified 96 patients with PHT (TRjet ≥2.5 m/sec by echo), suggesting a prevalence of 26.5%. However, since only 57% were screened by echo, this prevalence is grossly underestimated. Many echos documenting a TRjet ≥2.5 m/sec were interpreted by a cardiologist as NOT having PHT, likely because abnormal PAP in SCD are lower than in primary PHT. Of patients screened by echo, 46% had PHT (75 SS, 13 SC, 8 Sb-thal). Only 51% were identified by a clinician as having PHT, and only 4% were receiving treatment (chronic transfusion). Fifteen children had PHT. While 11 carried the diagnosis, none were on therapy. There was no difference in the percentage of adults vs. children screened by echo, however 56% of adults screened had PHT compared to 25% of children screened. Patients screened by echo were more likely to be male, homozygous for SS and were generally a sicker population. Patients found to have PHT were older (r=0.22, p<0.0001), and had a higher incidence of asthma, VOC episodes, gallbladder and renal disease, hepatitis C, smoking, alcohol and/or drug abuse, >LFTs, >creatinine, and more were on oxygen and/or hydroxyurea therapy compared to those without PHT. Surprisingly, history of ACS and splenectomy was similar in both groups. Comparing adults to children with PHT, more men than women were affected among adults (however more men were screened), while gender was equally distributed among children. Age of children with PHT ranged from 7–17 years (mean 12.6±3 years). Children were more likely to be homozygous for SS (14/15), carry the diagnosis of PHT, have a history of ACS (93% vs. 52%), and a higher incidence of sepsis (40% vs. 14%) than their adult counterparts. However they had fewer complications overall; renal and liver disease was rare, and less were transfused. Compared to children who do not have PHT, kids with PHT are more likely to have a history of ACS (93% vs. 63%), an abnormal CXR (87% vs. 57%), asthma (33% vs. 15%), >VOC events (60% vs. 39%), history of sepsis (40% vs. 9%), but less stroke (7% vs. 17%) and less transfusions including chronic transfusion (27% vs. 50%). It is possible that early transfusion secondary to a CNS event is protective against the development of PHT in children. Stepwise logistical regression modeling included renal disease, chronic transfusion, liver disease and alcohol use as significant risk factors for PHT (ROC = 0.82). Current mortality rate is 2% for patients without PHT vs. 8% for the PHT group (p=0.03). In conclusion, PHT is a common complication in SCD that affects both adults and children. The diagnosis is often missed, even with echo evidence of PHT. In this population 96% were untreated. Children with PHT have a different profile of complications than adults with PHT, suggesting alternate mechanisms of disease pathogenesis in children. Since PHT is associated with high mortality and morbidity, universal screening by echo and increased awareness is essential to identify patients at risk, and new therapies are critically needed.

Prevalence of Pulmonary Hypertension (PHTN) in Sickle Cell Disease (SCD) Adolescents with Pulmonary Complications.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3759-3759
Author(s):  
Onyinye C. Onyekwere ◽  
Andrew Campbell ◽  
James Williams ◽  
Peter Gaskin ◽  
Sohail Rana ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Pulmonary Complications ◽  
Acute Chest Syndrome ◽  
University Of Michigan ◽  
Cell Disease ◽  
Hemoglobin F ◽  
Howard University ◽  
History Of

Abstract Despite the high prevalence of PHTN in adults with SCD, the prevalence in the pediatric population with SCD is not known. We hypothesized that elevated pulmonary artery pressures may be found in SCD adolescents with history of pulmonary complications, such as acute chest syndrome (ACS), obstructive sleep apnea (OSA), asthma, and reactive airway disease. Thirty such sickle cell disease adolescents were screened at Howard University or University of Michigan for PHTN with Doppler echocardiography. We defined PHTN as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/sec (corresponding to a pulmonary artery systolic pressure greater than 35 mm Hg). PHTN was found in 16 SCD patients (53.3%) and 5 (16.7%) had TRV > 3.0 m/sec. Clinical findings according to the presences or absence of PHTN are shown in the table. Potential factors contributing to PHTN in patients with SCD include chronic hemolysis and chronic hypoxia. Our results suggest that PHTN is common among SCD adolescents with a history of pulmonary complications. Consideration should be given to screening such patients for PHTN and exploring treatment options. Further studies are urgently needed to clarify the prevalence and mechanisms of PHTN in adolescents with SCD. Clinical and demographic data of 30 SCD adolescents with pulmonary findings who underwent echocardiography at Howard University Hospital or University of Michigan PHTN (N = 16) No PHTN (N = 14) P Age in years (mean +/− SD) 15.9 +/− 3.2 17.4 +/− 2.3 0.17 Females (no. and %) 5 (31.3) 7 (50) 0.5 Hemoglobin SS Phenotype (no and %) 14 (87.5 11 (78.6) 0.5 Hemoglobin concentration (mean +/− SD) 8.0 +/− 2.1 9.3 +/−1.9 0.11 White blood cells (mean +/− SD) 10.9 +/− 2.9 9.7 +/− 3.7 0.4 Platelet (mean +/− SD) 475 +/− 172 364 +/− 240 0.17 Hemoglobin F percent (mean +/− SD) 5.1 +/− 3.5 6.4 +/− 5.5 0.6 Lactate dehydrogenase (mean +/− SD) 505 +/− 162 264 +/− 50 0.002 Total bilirubin (mean +/− SD) 4.1 +/− 2.6 3.4 +/− 2.6 0.5 Creatinine concentration (mean +/− SD) 0.6 +/− 0.2 0.7 +/− 0.2 0.18 Aspartate transaminase (mean +/− SD) 48 +/− 27 36 +/− 16 0.18 Alanine transaminase (mean +/− SD) 51 +/− 37 39 +/− 20 0.3

Abnormal Pulmonary Function in Adults with Sickle Cell Disease: Association of Decreased DLCO with Systemic Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 316-316 ◽  
Author(s):  
Elizabeth S. Klings ◽  
Diego F. Wyszynski ◽  
Vikki G. Nolan ◽  
Martin H. Steinberg
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Function ◽  
Sickle Cell ◽  
Pulmonary Function Tests ◽  
Systemic Disease ◽  
The United States ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Restrictive Physiology ◽  
Abnormal Pulmonary Function

Abstract Pulmonary complications of sickle cell disease (SCD), including acute chest syndrome, pulmonary hypertension (PH) and pulmonary fibrosis, are common. Dyspnea and hypoxemia are equally common in this population. It is likely that pulmonary function tests (PFT) are abnormal in the SCD population, however, no extensive study has been reported to date. Moreover, the relationship between abnormal pulmonary function and other manifestations of SCD, such as PH, is unclear. We hypothesized that abnormalities of pulmonary function, particularly a low diffusion capacity for carbon monoxide (DLCO), may be associated with other complications of SCD. The Cooperative Study of Sickle Cell Disease (CSSCD) enrolled and followed more than 4,000 SCD patients who had visited one of 23 participating clinical centers across the United States between 1978 and 1998. Data were collected on many complications of the disease, and standardized collection of PFTs were part of the protocol. From the more than 1300 CSSCD patients who had the results of PFTs recorded, 310 adults (age≥ 20 years of age) homozygous for the Hb S gene without coincident α thalassemia and with sufficient data were identified. Predicted values for FEV1, FVC, FEV1/FVC, TLC, RV and DLCO were calculated using algorithms that accounted for gender, age, and height in the African American population (using STATA, version 9); data are presented as percent predicted. Based on criteria established by the American Thoracic Society, subjects were sub-classified into 7 groups: obstructive physiology; restrictive physiology; mixed obstructive/restrictive disease; low lung volumes with normal spirometry (LLV); LLV with a low DLCO, isolated low DLCO, or normal. The association of blood counts and serum chemistries between patients with low DLCO compared with those with a normal DLCO was assessed by multivariate linear regression (using SAS software version 8.2). Normal PFTs were present in only 31 of 310 (10 %) SCD patients. Overall, the adult SCD population was characterized by decreased total lung capacities (70.2 + 14.7% predicted) and DLCO (64.5 + 19.9 % predicted adjusted for hemoglobin concentration). The most common PFT patterns observed were restrictive physiology (35.8%), LLV with normal spirometry (34.2% of patients), and an isolated low DLCO (12.9%). The presence of a low DLCO was associated with an elevated platelet count (p=0.05), hepatic dysfunction [elevated ALT (p=0.07) with elevated AST (p=0.01)] and renal dysfunction [elevated BUN and creatinine (p=0.05, 0.07)]. Restrictive disease is marginally associated with a decrease in hematocrit (p=0.07) and Hb F levels (p=0.07). Pulmonary function is abnormal in 90% of adult SCD patients. Common abnormalities include restrictive physiology, LLV with normal spirometry and a decreased DLCO. The presence of a decreased DLCO may be a marker of more severe systemic disease that includes impaired renal and hepatic function and possibly complications of hemolytic anemia such as PH.

Corrected QT Interval Is Related to Markers of Hemolysis and Tricuspid Regurgitant Jet Velocity in a Young Cohort with Sickle Cell Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2258-2258
Author(s):  
Robert I. Liem ◽  
Luciana T. Young ◽  
Alexis A. Thompson
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Qt Interval ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Qtc Prolongation ◽  
Corrected Qt Interval ◽  
Conduction Abnormalities ◽  
History Of ◽  
Tricuspid Regurgitant Jet Velocity

Abstract Recent evidence suggests that prolongation in QT interval may be a frequent finding in patients with sickle cell disease (SCD). Few studies, however, have examined the relationship between conduction abnormalities and other cardiac complications, such as left ventricular hypertrophy (LVH) and tricuspid regurgitant jet velocity (TRJV) elevation, in this population. Moreover, long QT may be a marker of increased mortality in conditions, other than SCD, associated with LVH. We therefore sought to evaluate QT interval and its relationship to echocardiographic findings, laboratory parameters and disease severity in a cohort of children and young adults with SCD. Methods We prospectively evaluated the corrected QT interval (QTc) on standard 12-lead ECG in a cross-sectional, convenience sample of 73 subjects (41 males, mean age 14.2±3 years, range 10 to 24) with Hb SS, SC and S-β0 thalassemia undergoing screening for TRJV elevation. Subjects on chronic transfusions were excluded and all studies were performed at baseline on the same day. A review of available medical records was also performed. Results In our cohort, QTc (mean 436±24 ms, range 387 to 531) was prolonged &gt; 440 ms in 30/73 (41%) of subjects at steady state. We also found TRJV elevation ≥ 2.5 m/s in 24/73 (33%) and LVH by ECG or echocardiographic criteria in 32/73 (44%) subjects. Using Pearson’s correlation coefficient, we observed significant correlations between QTc and TRJV (r=0.38, p=0.002), WBC (r=0.37, p=0.001) and several markers of hemolysis, including LDH (r=0.46, p=0001), Hb (r=-0.32, p=0.005), retic (r=0.29, p=0.013), plasma Hb (r=0.27, p=0.03) and AST (r=0.38, p=0.001). Using Student’s t-test for independent samples, only TRJV (2.55±0.33 vs. 2.34±0.26 m/s, p=0.006), LDH (450±166 vs. 329±143 U/L, p=0.001), WBC (10.6±4.7 vs. 8.6±3.3×109/L, p=0.048), retic (14.4±9.2 vs. 10.6±6.1%, p=0.039) and AST (50±22 vs. 38±15 U/L, p=0.009) were significantly higher and Hb (9.1±1.3 vs. 9.9±1.7 g/dL, p=0.04) lower in subjects with QTc &gt; 440 ms compared to those with QTc ≤ 440 ms. We found no significant relationship between QTc and age, LV mass, platelet count or fetal Hb. By χ2 analysis, a larger proportion of subjects with QTc &gt; 440 ms also had a history of acute chest syndrome (p=0.007), gallstones (p=0.047), exchange transfusion (p=0.04) and to a less significant degree, TRJV elevation (p=0.112). Prolonged QTc was not affected by sex, hydroxyurea use or a history of LVH, frequent pain, asthma, splenectomy, priapism and tonsilloadenoidectomy. Given sample size limitations and data reduction methods, we found by logistic regression analysis that the combination of TRJV and history of acute chest syndrome best predicted QTc prolongation, correctly identifying 80% of cases and resulting in positive and negative predictive values of 76% and 81%, respectively. Conclusions We conclude that QTc prolongation is common in a prospectively screened cohort of young sickle cell patients at baseline and is associated with evidence of hemolysis and to a lesser degree, TRJV elevation. Our results contrast with findings in other conditions that link QTc prolongation primarily to LVH. Future studies will be critical to further define QTc variability, pathophysiologic determinants as well as the clinical consequences of conduction abnormalities, which may or may not relate to TRJV elevation, in the sickle cell population.

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.

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