Retrospective Review of the Natural History of Pulmonary Hypertension in Sickle Cell Disease Demonstrates That Progressive Enlargement of the Left Atrium Is a Strong Predictor of Death.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1529-1529
Author(s):  
Damian Silbermins ◽  
Agustin Calatroni ◽  
Jude Jonassaint ◽  
Marilyn J. Telen ◽  
Laura M. De Castro
Keyword(s):  
Pulmonary Hypertension ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Natural History ◽  
Retrospective Review ◽  
Strong Predictor ◽  
Cell Disease ◽  
Risk Of Death ◽  
Rate Of Progression ◽  
History Of

Abstract Abstract 1529 Poster Board I-552 Pulmonary hypertension (PAH) is an independent risk factor for death in sickle cell disease (SCD). We performed a retrospective chart review to determine the natural history of PAH in our adult SCD population. We hypothesized that increased pulmonary artery pressures seen during hospitalizations for painful crisis or acute chest syndrome would be reflected in a faster progression of PAH measured during steady state. We reviewed charts and echocardiograms of 362 patients seen at Duke University from January 1980 to March 2009. A total of 878 2D echocardiograms were reviewed, with 196 patients having 2 or more echocardiographic procedures. Fifth-three of the 81 patients who died during this period had had at least 2 or more echocardiograms. Studies were considered done at steady state if they were performed as an outpatient procedure. Out of 878 total echocardiograms, 460 had either no measurable tricuspid regurgitation jet (TR) or failed to report it and were excluded from further analysis, leaving 418 echocardiograms in 252 patients (167 at steady state and 251 as inpatient). Among patients with multiple echocardiograms and measurable TR jet performed at steady state, we used a linear mixed model to identify a mean yearly rate of progression of 0.04 m/s (p<0.001, 95% CI 0.02 to 0.05). Patients in whom echocardiograms were performed as inpatients had higher pressures (mean difference 0.24 m/s, p<0.01), as reported previously by other authors, but they had a similar rate of progression at steady state as did the patients without inpatient echocardiograms (Figure 1). Contrary to our hypothesis, therefore, higher inpatient TR jet velocities did not affect the rate of progression of PAH at steady state. Furthermore, the rate of progression of TR jet velocity at steady state was also not statistically significantly related to mortality (p=0.57). Interestingly, however, patients who died had an inpatient TR jet velocity slope of 0.08 m/s/year, compared to patients who were alive at the end of the study period (0.03 m/s/year, p=0.04). Furthermore, in patients with PAH, an increase in the left atrial diameter of 1 cm increased the risk of death by 50% (OR 1.47, p=0.001). Despite the potential selection bias inherent to a retrospective review, our study was able to estimate a mean progression of PAH of 0.04 m/s year in SCD patients at steady state and to identify increasing left atrium enlargement as a strong predictor of death. In this cohort, findings of a faster progression of PAH, measured by inpatient echocardiograms, did not correlate with changes in the rate of progression of PAH at steady state, although it was associated with an increased risk of death. Improved knowledge of variables characterizing the natural history of PAH in SCD patients should support further development of therapeutic approaches targeting PAH. Disclosures No relevant conflicts of interest to declare.

Pulmonary Hypertension Is Not Associated with An Increased Risk of Death in Children with Sickle-Cell Disease Followed for a Mean of 3 Years.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1443-1443
Author(s):  
Margaret T. Lee ◽  
Tania Small ◽  
Muhammad Amar Khan ◽  
Erika Berman Rosenzweig ◽  
Robyn J. Barst ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Pulmonary Hypertension ◽  
Platelet Count ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of

Abstract To determine if pulmonary hypertension (PH) is associated with increased mortality in children with sickle-cell disease (SCD), we prospectively followed 88 pediatric patients for a mean of 3 years after echocardiographic screening for PH. Subjects (45 males, 43 females) were 5–20 years old (median 13) at initial screening and included 59 SS, 23 SC, 4 S/β0Thalassemia, 1 S/β+Thalassemia and 1 S/HPFH. PH was defined as tricuscipid regurgitant jet velocity (TRV) of ³2.5 m/s. Of the 88 subjects, 18 (20%) had TRV ³2.5 m/s (median 2.6, range 2.5–3.1). Subjects with PH ranged from 7 to 19 years old (median 15), were predominantly male (12 of 18) and included 14 (78%) SS, 2 SC, 2 S/β0Thalassemia. After a mean follow-up of 36.3 ± 9.4 (SD) months, all 18 patients with PH were alive. None had received specific treatment for PH; one had undergone a successful bone marrow transplant from a matched sibling donor. After a mean follow-up of 33.5 ± 13.3 months, 67 subjects with normal TRV were alive; 3 had been lost to follow-up. To compare risk factors for PH in our children with those reported for adults, we reviewed the clinical data for our subjects. Children with PH had significantly increased serum lactate dehydrogenase (LDH; P=0.04), higher platelet count (P=0.02), and, in males, a history of priapism (P=0.009). No significant differences were observed with respect to age, gender, sickle-cell type, white blood cell count, hemoglobin, reticulocyte count, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, ferritin, history of painful crisis, acute chest syndrome, asthma, splenectomy, or hydroxyurea therapy. To further examine the association of PH and hemolysis, a subanalysis was done excluding 18 chronically transfused patients because transfusion can alter laboratory indicators of hemolysis. Independent variables with P≤0.1 on univariate analysis (LDH, female gender, and platelet count) were entered into a logistic regression model. Only LDH was independently associated with PH (Odds Ratio=1.6, 95% CI=1.2–2.1, P=0.004). Our results show that PH diagnosed by Doppler echocardiography was not associated with an increased risk of death in children with SCD followed for a mean of 3 years. A greatly increased risk of death (rate ratio, 10.1) has been reported in adults followed for a mean of 1.5 years (N Eng J Med2004;350:886–95). In our children, as in the adults, increased LDH, a marker of hemolysis, and, in males, a history of priapism were associated with PH. By contrast, our children with PH did not have increases in serum creatinine, direct bilirubin, alkaline phosphatase and ferritin that have been linked epidemiologically to PH in adults with SCD (Pediatr Hematol Onc2007;24:159–70). These findings suggest that PH of itself may not be a direct cause of death in SCD. Rather, PH may be a manifestation of progressive, cumulative organ damage resulting from chronic hemolysis and systemic vasculopathy that ultimately leads to increased mortality in adulthood. Early recognition and preventive therapy for increased hemolysis may be needed to avert premature death in adults with SCD.

The natural history of sickle cell disease

1998 ◽  
Vol 10 (1) ◽  
pp. 49-52 ◽  
Author(s):  
Carolyn Hoppe ◽  
Lori Styles ◽  
Elliott Vichinsky
Keyword(s):  
Sickle Cell Disease ◽  
Natural History ◽  
Sickle Cell ◽  
Cell Disease ◽  
History Of

Mortality in Children and Adolescents With Sickle Cell Disease

PEDIATRICS ◽  
1989 ◽  
Vol 84 (3) ◽  
pp. 500-508 ◽  
Author(s):  
Sanford L. Leikin ◽  
Dianne Gallagher ◽  
Thomas R. Kinney ◽  
Desirée Sloane ◽  
Panpit Klug ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Natural History ◽  
Parental Education ◽  
Young Patients ◽  
Cell Disease ◽  
Cerebrovascular Accidents ◽  
Limited Success ◽  
History Of ◽  
Overall Mortality

A study of the natural history of sickle hemoglobinopathies was begun in March 1979. By August 1987, a total of 2824 patients &lt;20 years of age were enrolled. There have been 14 670 person-years of followup. Seventy-three deaths have occurred. Most of the deaths were in patients with hemoglobin SS. The peak incidence of death was between 1 and 3 years of age, and the major cause in these young patients was infection. Cerebrovascular accidents and traumatic events exceeded infections as a cause of death in patients &gt; 10 years of age. There was limited success in identifying risk factors for death. Comparison of this study's overall mortality of 2.6% (0.5 deaths per 100 person-years) with previous reports indicates improvement of survival in US patients &lt;20 years of age with sickle hemoglobinopathies. This improvement is most likely due to parental education and counseling about the illness and the early institution of antibotics in suspected infections.

scholarly journals Pulmonary hypertension in sickle cell disease: diagnosis and management

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 425-431 ◽  
Author(s):  
Kenneth I. Ataga ◽  
Elizabeth S. Klings
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Disease Diagnosis ◽  
Adult Patients ◽  
Heart Catheterization ◽  
Cell Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
High Prevalence

Abstract The increased survival of patients with sickle cell disease (SCD) into adulthood is associated with an increased incidence of multiorgan dysfunction and a progressive systemic and pulmonary vasculopathy. The high prevalence of an elevated tricuspid regurgitant jet velocity and its association with an increased risk of death in adult patients is well established. However, there has been controversy regarding the prevalence of pulmonary hypertension (PH) and its association with mortality in SCD. Multiple recently published reports demonstrate that PH as diagnosed by right heart catheterization is common in adult SCD patients, with a prevalence of 6%–11%. Furthermore, PH is associated with an increased risk of death in SCD patients. In this chapter, we provide evidence for the high prevalence of PH in SCD and its association with mortality and make recommendations for its evaluation and management. Finally, we provide the rationale for screening for this life-threatening complication in adult patients with SCD.

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.

Natriuretic Peptide Levels Correlate with Pulmonary Pressures and Prospective Mortality in SCD: Use of This Biomarker To Identify Prevalence and Mortality of Pulmonary Hypertension in the MSH Cohort.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1-1
Author(s):  
Roberto Machado ◽  
Martin Steinberg ◽  
Duane Bonds ◽  
Samir Ballas ◽  
William Blackwelder ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cell Disease ◽  
Risk Of Death ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Abstract Pulmonary hypertension [PH-tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s] is a common complication of sickle cell disease associated with high mortality. Identification of biomarkers of PH and mortality could facilitate screening and risk stratification in this population. Validated biomarkers would provide methods for retrospective evaluation of the prevalence and prognosis of PH in large historical cohorts of patients such as the Multicenter Study of Hydroxyurea in Sickle Cell Anemia(MSH). Because brain natriuretic peptide(BNP) is released from the ventricles during pressure strain, we hypothesized that BNP levels would correlate with the severity of PH and prospective risk of death in patients with SCD. BNP was measured in 45 African-American control subjects and 230 patients with SCD. Median (interquartile range) BNP(pg/ml) was higher in patients with PH than patients without PH or controls[+PH: 206(81–701),-PH: 47(26–104), C: 29, P&lt;0.001]. BNP levels directly correlated with age (R=0.32, P&lt;0.001), creatinine (R=0.22, P&lt;0.001), LDH(R=0.31, P&lt;0.001), TRV (R=0.5, P&lt;0.001), pulmonary vascular resistance (R=0.5, P=0.001); and inversely with hemoglobin(R=0.41, P&lt;0.001), cardiac output(R=0.47, P= 0.003) and 6-minute walk distance(R=0.51, P=0.001). The area under the ROC for BNP and the diagnosis of pulmonary hypertension was 0.84 (P&lt;0.001). A cutoff value of 160 pg/ml (corresponding to the 75th percentile for the population) had 58% sensitivity and 98% specificity for the diagnosis of PH. Cox proportional hazards regression identified BNP as an independent predictor of mortality(RR 2.17,95% CI 1.2–3.8, P =0.001) with clear mortality break point at the 75th percentile(160 pg/ml). To independently explore the prevalence and associated risk of PH in patients with sickle cell disease, a BNP value of 160 pg/ml was used as an indicator of PH. BNP levels were then measured in plasma samples collected in 121 patients who were enrolled in the MSH patient’s follow-up study that started in 1996. These patients had received hydroxyurea or placebo for two years, had moderately severe disease based on study entry criteria, and had 9-years of comprehensive follow-up. An abnormal BNP level ≥160 pg/ml was present in 30% of patients in the MSH cohort. BNP levels correlated directly with age(R=0.35, P&lt;0.001) and creatinine (R=0.24, P&lt;0.001), and inversely with hemoglobin(R=−0.54, P&lt;0.001). There was no correlation between BNP and rate of painful episodes or acute chest syndrome, use of hydroxyurea or leukocyte count. A high BNP level in the MSH cohort was associated with mortality by logistic regression(OR 3.04,95% CI 1.2–7.6, P = 0.018) and Cox proportional hazards regression analysis(RR 2.87, P=0.017). The relationship remained significant for continuous log- transformed BNP values and after adjustment for other covariates. These studies confirm that PH is common, mechanistically linked to hemolytic anemia and the major risk factor for death in SCD. Provocatively, the MSH analysis suggests that rates of pain episodes in this small sample of seriously ill patients were unrelated to risk of death: this risk was largely determined by a high BNP level, which is probably explained by undiagnosed hemolysis-associated PH.

Severity of Sickle Cell Disease: Modeling Interrelationships among Hemolysis, Pulmonary Hypertension and Risk of Death.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 786-786
Author(s):  
Paola Sebastiani ◽  
Vikki G. Nolan ◽  
Clinton T. Baldwin ◽  
Maria M. Abad-Grau ◽  
Ling Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Risk Of Death

Abstract A single point mutation in the β hemoglobin gene causes sickle cell disease (SCD), but patients have extremely variable phenotypes. Hemolysis-related complications include pulmonary hypertension (PHT), priapism, stroke and leg ulceration; blood viscosity and sickle vasoocclusion are associated with painful episodes, acute chest syndrome and osteonecrosis. Predicting who is at highest risk of death would be useful therapeutically and prognostically. Applying Bayesian network modeling that describes complex interactions among many variables by factorizing their joint probability distribution into modules, to data from 3380 SCD patients, we constructed a disease severity score (DSS: 0, least severe; 1, most severe), defining severity as risk of death within 5 years. A network of 24 variables described complex associations among clinical and laboratory complications of SCD. The analysis was validated in 140 patients whose SCD severity was assessed by expert clinicians and 210 adults where severity was also assessed by the echocardiographic diagnosis of PHT and death. Information about PHT allowed a comparison of the DSS with the tricuspid regurgitant jet velocity (TRJV), an objective marker of PHT and an independent risk factor for death. DSS and three indices of clinical severity (severity ranking of individuals by expert clinicians; objective measurement of the presence and severity of PHT; risk of prospective death) were correlated. Among living subjects, the median score was 0.57 in 135 patients without PHT, 0.64 in 40 patients with mild PHT and 0.86 in 15 patients with severe PHT. The difference in average score between living patients with and without PHT is significant. The same increasing trend was noticeable in the subjects who died during follow-up: 0.60 in subjects without PHT; 0.68 in subjects with mild PHT; 0.79 in subjects with severe PHT. The utility of the DSS is also supported by the ability to assign a score to subjects for whom the TRJV cannot be measured. Surprisingly, besides known risk factors like renal insufficiency and leukocytosis, we identified the intensity of hemolytic anemia and clinical events associated with hemolytic anemia as contributing to risk for death. Priapism, an excellent reflection of the hemolytic anemia-related complications of SCD, is associated with PHT and its association with death was unexpected. Laboratory variables predictive of disease severity included LDH and reticulocytes that reflect the intensity of hemolytic anemia. Elevated systolic blood pressure increased the odds of death by 3.4, consistent with hypertension as a marker of early death in SCD. Subjects with sickle cell anemia are at greatest risk compared with subjects with sickle cell anemia-α thalassemia and with subjects with HbSC disease. Our model suggests that the intensity of hemolytic anemia, estimated by LDH, reticulocyte count and AST, and shown previously to be associated with PHT, priapism, leg ulceration and possibly stroke, is an important contributor to death. This model can be used to compute a personalized measure of disease severity that might be useful for guiding therapeutic decisions and designing clinical trials.

NT-Pro Brain Natriuretic Peptide Levels and the Risk of Stroke and Death in the Cooperative Study of Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1541-1541 ◽  
Author(s):  
Roberto F Machado ◽  
Mariana Hildescheim ◽  
Laurel Mendelsohn ◽  
Gregory J Kato ◽  
Mark T Gladwin
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Incidence Rate ◽  
Sickle Cell ◽  
Pediatric Patients ◽  
Cooperative Study ◽  
Cell Disease ◽  
Risk Of Death ◽  
History Of

Abstract Abstract 1541 Poster Board I-564 Background Elevations in NT-proBNP levels are associated with hemolysis-associated pulmonary hypertension and mortality in adults with sickle cell disease. The association of this vasculopathy with the risk of stroke has not been explored. The Cooperative Study of Sickle Cell Disease (CSSCD) is the largest cohort of adult and pediatric patients with sickle cell disease with the longest median follow-up. Using stored plasma samples from patients enrolled in the CSSCD, we tested the hypothesis that adult patients with high levels of NT-proBNP would be at a high risk of death and stroke and that pediatric patients with a high BNP might be at a high risk of stroke. Methods A threshold NT-pro-BNP value previously identified to predict mortality in adults with sickle cell disease was used to determine the association between the risk of stroke and mortality in a cohort of 758 participants (pediatric cohort, n=428 and adult cohort, n=330) in the CSSCD. Results The prevalence of an abnormal NT-proBNP level ≥ 160 pg/ml was 27.6 % in patients in the adult CSSCD cohort. The prevalence of a NT-proBNP level ≥ 160 pg/ml was 27.4 % in the pediatric cohort, which is at least in part explained by known higher normal NT-proBNP levels in children, especially during the first year of life. The incidence of the development of a high NT-proBNP level in subjects with a normal baseline level was 6 % over a mean follow-up time of 5.9 years (incidence rate per 100-person years of 1.03) in the pediatric cohort and 16.5 % over a mean follow-up time of 1.9 years in the adult cohort (incidence rate per 100-person years of 8.59). In subjects with normal baseline levels, multivariate logistic regression analysis of clinical and laboratory factors associated with the development of a high NT-proBNP level included increasing age (OR 3.43, 95% CI 1.6-7.2, P = 0.001), low hemoglobin (OR 0.47, 95% CI 0.3-0.7, P < 0.001), high white blood cell count (OR 1.69, 95% CI 1.05-2.7, P = 0.03), high creatinine (OR 2.22, 95% CI 1.1-4.3, P = 0.02), blood urea nitrogen (OR 1.64, 95% CI 1.2-2.3, P = 0.004), alanine aminotransferase (OR 1.26, 95% CI 1.01-1.6, P = 0.04) and uric acid levels (OR 2.32, 95% CI 1.4-3.8, P = 0.001), and history of leg ulcers (OR 7.46, 95% CI 2.0-28.5, P = 0.003). Elevated NT pro-BNP levels were associated with indices of hemolytic anemia (hemoglobin: OR 0.33, 95% CI 0.2-0.4, P < 0.001) and a history of stroke (OR 1.86, 95% CI 0.9-3.7, P = 0.02). An NT-pro-BNP level ≥160 pg/ml was a predictor of mortality (RR 6.24, 95% CI 2.9-13.3, P < 0.001) and stroke (RR 3.84, 95 % CI 1.0-14.3, P = 0.05) in this cohort. Conclusions A high NT-proBNP level is a major risk factor for death in patients with sickle cell disease. These findings provide further support for a mechanistic link between hemolytic anemia and the development of cardiovascular complications in this patient population. Finally, we have identified a novel widely available biomarker of the risk of death and stroke in sickle cell disease. Disclosures No relevant conflicts of interest to declare.

Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4819-4819
Author(s):  
Rodolfo D Cancado ◽  
Maria Cristina A Olivato ◽  
Newton Nunes Lima Filho ◽  
Orlando Campos ◽  
Carlos Chiattone
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Systolic Pressure ◽  
Pulmonary Artery Systolic Pressure ◽  
Cell Disease ◽  
Risk Of Death ◽  
Hydroxyurea Therapy

Abstract Pulmonary hypertension develops in most forms of hereditary and chronic hemolytic anemia, including sickle cell disease, thalassemia, hereditary spherocytosis, and paroxysmal nocturnal hemoglobinuria, suggesting that there is a clinical syndrome of hemolysis-associated pulmonary hypertension. Retrospective studies from tertiary care referral centers suggest a prevalence of pulmonary hypertension in adults with sickle cell disease ranging from 20 to 40%. Despite the fact the elevations in pulmonary artery pressures are slight, morbidity and mortality are high. In adult sickle cell anemia patients, pulmonary hypertension is emerging as a major risk factor for death. We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 80 consecutive patients (20 men and 60 women; mean [±SD] age, 30 ± 10.8 years) between 1/20/2006 and 1/20/2008. The genotype on the basis of hematologic and hemoglobin characteristics was hemoglobin SS in all patients. Pulmonary hypertension was prospectively defined as a tricuspid regurgitant Jet velocity (TFJV) of at least 2.5 m per second. Patients were followed for a mean of 18 months (6–24 months), and data were censored at the time of death or loss to follow-up. Doppler-defined pulmonary hypertension occurred in 37.5 percent of patients (30/80). Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified age, female sex, deferasirox therapy, left ventricular mass index, pulmonary artery systolic pressure, reticulocytes, white-cell count, platelet count, lactate dehydrogenase (a marker of hemolysis), blood urea nitrogen, creatinine, uric acid and self-reported history of cardiovascular complication, billiary stones, retinopathy and acute chest syndrome, as significant independent correlates of pulmonary hypertension. The hemoglobin level, fetal hemoglobin level, hydroxyurea therapy and serum ferritin level were unrelated to pulmonary hypertension. Hazard rate for death according to the TFJV of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was associated with an increased risk of death (0.00 versus 2.54; P=0.998). Mortality rate in 24 months was 6.7% (2/30) for patients with TRJ velocity ≥ 2.5 m/sec versus 0.0% (0/50) for patients without pulmonary hypertension. Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Large trials evaluating the effects of treatment for pulmonary hypertension in the sickle cell anemia population are indicated.

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