scholarly journals Treatment dilemmas: strategies for priapism, chronic leg ulcer disease, and pulmonary hypertension in sickle cell disease

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 411-417
Author(s):  
Roberta C.G. Azbell ◽  
Payal Chandarana Desai
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Leg Ulcers ◽  
Cell Disease ◽  
Ulcer Disease ◽  
Multiorgan Disease ◽  
Chronic Hemolytic Anemia

Abstract Sickle cell disease is a disorder characterized by chronic hemolytic anemia and multiorgan disease complications. Although vaso-occlusive episodes, acute chest syndrome, and neurovascular disease frequently result in complication and have well-documented guidelines for management, the management of chronic hemolytic and vascular-related complications, such as priapism, leg ulcers, and pulmonary hypertension, is not as well recognized despite their increasing reported prevalence and association with morbidity and mortality. This chapter therefore reviews the current updates on diagnosis and management of priapism, leg ulcers, and pulmonary hypertension.

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.

Association of Pulmonary Hypertension with Sickle Cell Disease Subtypes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4824-4824
Author(s):  
Alice J. Cohen ◽  
Chaim Tuckman-Vernon
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Doppler Echocardiography ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Hemoglobin C ◽  
Baseline Hemoglobin

Abstract Pulmonary hypertension (PH) is a common complication of sickle cell disease (SD) and a significant cause of morbidity and mortality. PH, measured by Doppler echocardiography and defined as a tricuspid regurgitant jet velocity (TRV) > 2.5 m per second (m/s), is hypothesized to be related to the chronic hemolytic anemia of SD, but causality is unproven. If so, the presence of hemoglobin C, which reduces hemolysis, would be expected to have a reduced likelihood of PH. This study reviewed the prevalence of PH in 3 categories of patients with SD: homozygous S (SS), sickle-beta thalassemia (SB), and SC. Methods: Sickle cell disease patients registered at a state funded community comprehensive care adult sickle cell center were routinely screened for PH by Doppler echocardiography. The presence of PH, the incidence of a related complication, acute chest syndrome (ACS), and baseline hemoglobin (hgb) were reviewed. Results: 16 patients with SC type, 30 with SS and 39 with SB disease underwent screening. The prevalence of PH, ACS and hgb are listed in the table below. Conclusion: SC patients have PH and ACS similar to patients with SS and SB patients. These patients have higher baseline hemoglobin and may have hyperviscosity as a cause of PH and ACS as opposed to hemolytic anemia. Further study of PH and ACS in SC patients is warranted. SC SS SB p value PH 6/16 (38%) 12/40 (40%) 11/39 (28%) p= NS ACS 7/16 (44%) 10/30 (33%) 19/39 (49%) p=NS PH + ACS 4/16 (25%) 5/30 (17%) 4/39 (10%) p=NS ACS in PH patients 4/6 (67%) 5/12 (42%) 4/11 (36%) p-=NS Hgb 10.8 7.89 8.57 p=0.000

scholarly journals Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti-human parvovirus B19 IgG antibodies and the developement aplastic crises

2002 ◽  
Vol 44 (4) ◽  
pp. 187-190 ◽  
Author(s):  
Anadayr L.M. SANT'ANNA ◽  
Rita de Cássia N. Cubel GARCIA ◽  
Mônica MARZOCHE ◽  
Heloisa Helena A. Gallo da ROCHA ◽  
Maria Tereza M. PAULA ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Igg Antibodies ◽  
Cell Disease ◽  
Antibody Prevalence ◽  
Igg Antibody ◽  
Chronic Hemolytic Anemia

The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera from 165 chronic hemolytic anemia patients, receiving medical care at Instituto Estadual de Hematologia (IEHE), Rio de Janeiro, during the year of 1994. This sample represents around 10% of the chronic hemolytic anemia patients attending at IEHE. Most of these patients (140) have sickle cell disease. Anti-B19 IgG antibodies were detected in 32.1% of patients. No statistically significant difference (p > 0.05) was seen between IgG antibody prevalence in male (27.8%) and female (35.5%) patients. Anti-B19 IgG antibodies were more frequent in older (37.6%) than younger (28.2%) than 20 years old patients, although this difference had no statistical significance (p > 0.05). Anti-B19 IgG antibody prevalence showed that 67.9% of patients enrolled in the study were susceptible to B19 acute infection. With the aim to detect acute B19 infection, patients follow up continued until February 1996. During this period four patients presented transient aplastic crisis due to human parvovirus B19 as confirmed by the detection of specific IgM antibodies. All four patients were younger than 20 years old, and 3 were younger than 10 years old. Three of them were sickle cell disease patients. Three of the four acute B19 infection occurred during 1994 springtime.

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.

Leg Ulcers among Patients with Sickle Cell Disease on Hydroxyurea Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1676-1676
Author(s):  
Suresh Mendpara ◽  
Betsy Clair ◽  
Mudusar Raza ◽  
Lisa Daitch ◽  
David Smith ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Therapeutic Agent ◽  
Acute Chest Syndrome ◽  
Prior History ◽  
Leg Ulcers ◽  
Cell Disease ◽  
Number Of Patients ◽  
Transfusion Requirements ◽  
History Of

Abstract Leg ulcers remain a debilitating complication of Sickle Cell Disease (SCD): significant pain, tendency to polymicrobial infection, difficult to heal, and tendency to recur in ~ 50% of patients. According to CSSCD data, 2.5% of 2075 patients had leg ulcers at study entry; overall incidence was 9.97 per 100-person years in patients without concomitant alpha thalassemia (thal), and 5.73 per 100 person years in those with alpha thal. Hydroxyurea (HU) is an approved therapeutic agent for adults with SCD; it has been shown to decrease frequency of pain crises and acute chest syndrome and decrease transfusion requirements. Recently, HU was associated with a 40% reduction in mortality. There have been reports of an association between HU therapy and leg ulcers in patients with myeloproliferative disorders (MPD) and more recently with SCD. A retrospective study from the Mayo Clinic (Best et al, Ann. Intern. Med., 128:29, 1998) found that among 115 patients with various forms of MPD, 14 developed leg ulcers after an average HU exposure of 6 years; all ulcers healed after stopping HU, and 2 patients had recurrences of their ulcers after resuming HU. Chaine et al (Arch. Dermatol, 137: 467, 2001) reported that 5/17 (29%) patients with SCD on HU developed leg ulcers. If HU, the most effective available therapeutic agent for SCD is indeed causative of leg ulcers, this should raise serious concerns. In an effort to further clarify this problem, we performed a retrospective analysis. 421 adult SCD patients (age 16–60) formed the subject of this study. 152 were treated with HU for a minimum of 6 months. 269 patients were not exposed to HU. A total of 25 patients (5.9%) had leg ulcers; 17 were treated with HU, 8 were not. Thus, the frequency of leg ulcers was 11.2% among HU treated patients, as opposed to 2.9% among those who did not receive HU therapy (p<0.001). However, of the 17 patients with ulcers, 16(94%) had a history of ulcers prior to HU exposure. Only one patient developed ulcers for the first time after starting HU therapy. 6/17 patients experienced healing of their ulcers despite continuing HU. Among the patients treated with HU, those who had ulcers were more anemic (pre-treatment Hb 7.4 vs 8.2 g/dl, p=0.01) and were older (mean age 40.5 vs 33.0, p<0.001), confirming previous observations. Logistic regression analyses showed that only age and prior history of leg ulcers were significant risk factors for the development of ulcers in patients with SCD under HU therapy. Our data on a large number of patients does not suggest that HU therapy alone is causative of leg ulcers in SCD patients. The supporting evidence for this conclusion comes from our observations that 1) a vast majority of patients (16/17; 94%) who developed leg ulcers after starting HU had a previous history of ulcers. This is also true of the report by Chaine et al, where 4/5 patients with leg ulcers had a prior history; 2) in 6/17 patients (35.3%) ulcers healed with conventional therapy despite continuation of HU. Furthermore, it should be noted that patients with leg ulcers represent a more severe group and are thus more likely candidates for HU therapy. We conclude that HU therapy alone is not causative of leg ulcers in patients with SCD. In addition, HU does not appear to prevent recurrence of leg ulcers in patients with a prior history; nor does it expedite ulcer healing. Other as yet unknown factors, some of which are likely genetic, play an important role in determining the risk for developing leg ulcers.

Pulmonary Hypertension in Children and Adolescents with Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3787-3787 ◽  
Author(s):  
Aziza Sedrak ◽  
Sreedhar P. Rao ◽  
Scott T. Miller ◽  
Vahid Hekmet ◽  
Madu Rao
Keyword(s):  
Obstructive Sleep Apnea ◽  
Pulmonary Hypertension ◽  
Sleep Apnea ◽  
Sickle Cell Disease ◽  
Pulmonary Function ◽  
Sickle Cell ◽  
Pulmonary Function Tests ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Obstructive Sleep

Abstract Pulmonary hypertension occurs in 20–40% of adults with sickle cell disease and has a poor prognosis; age of onset and prevalence in childhood are not well established. In adults, recurrent acute chest syndrome is associated with chronic sickle cell lung disease and perhaps pulmonary hypertension. Hematologically normal children with obstructive sleep apnea are at risk for pulmonary hypertension. We sought to determine the prevalence of pulmonary hypertension in children and adolescents with sickle cell disease, explore potential association with abnormal pulmonary function or sleep apnea, and identify other clinical or laboratory factors associated with this potentially life-threatening complication. Forty-eight patients (age 5–21 years, median 12 years) consented to participate. Thirty-eight (79%) had Hb SS; five each had Hb SC and S-beta thalassemia (three beta plus and two beta zero) (10.4%). Eleven (22.9%) were on chronic transfusion (seven for stroke, three for abnormal TCD velocity screening, and one for recurrent pain crises); nineteen (39.5%) were on hydroxyurea (ten for recurrent acute chest syndrome and nine for recurrent pain). A detailed history and physical examination were done on all enrolled subjects (history was comprehensive, but specifically included cardiopulmonary symptoms; neurological problems; number of pain crises and acute chest syndrome; blood transfusions; use of hydroxyurea; and a screening for obstructive sleep apnea). If apnea history was suggestive, polysomnography was done. In addition, all study subjects had Doppler echocardiography and pulmonary function tests (PFT). Pulmonary hypertension was defined as an age and body mass index-adjusted tricuspid regurgitant jet velocity (TRV) of greater than 2.5 mm/sec. Among the study group, 31 (64.5%) had pulmonary function tests; 17 (54.8%) had restrictive abnormalities on PFT, three (9.6%) had obstructive changes and 11 (35.4%) had normal PFT. Three patients (6.2%) had a history suggestive of apnea, then polysomnography; one was normal and two had OSA. Four of the 48 patients (8.3%) had PHT (TRV values 2.52, 2.55, 2.61, and 2.91). All had Hb SS. Two were age 17 and 18 years and two were 10 and 11. All were asymptomatic. One had restrictive PFT and none had OSA. There was no correlation between the presence of PHT and pulmonary function abnormalities or sleep apnea. Of the various other clinical and laboratory parameters examined, only an elevated serum indirect bilirubin was associated with PHT; there was a trend toward association with elevated reticulocyte count and low fetal Hb levels. In summary, the prevalence of PHT our pediatric sickle cell population is 8.3%. As reported in adults, there may be an association between PHT and more severe hemolysis. We could find no association with abnormal pulmonary function or obstructive sleep apnea. Characteristics of study patients PHT No PHT P Value Fetal Hb(%) (Mean) 3.7 7.9 .154 Age (Mean) 13.5 years 12 years .564 Reticulocytes (%) 13.8 8.25 .087 Indirect bilirubin (mg/dl) (Mean) 5.4 2.2 .027

Lack of Clustering of SCD Complications Into Two Distinct Subphenotypes In An Adult Patient Population.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1643-1643 ◽  
Author(s):  
Jigarkumar Parikh ◽  
Thomas Kochaparambil ◽  
Hongyan Xu ◽  
Betsy Clair ◽  
Kavita Natarajan ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Principal Components ◽  
The Other ◽  
Leg Ulcers ◽  
Cell Disease ◽  
Factor Map ◽  
Pathophysiologic Mechanisms

Abstract Abstract 1643 The complex pathophysiologic mechanisms that contribute to disease pathology in sickle cell disease (SCD) include microvascular occlusion secondary to deoxy-Hb S polymerization, interaction of sickle RBCs with vascular endothelium and other blood cells, hemolysis with resultant nitric oxide (NO) scavenging, endothelial activation with inflammation, and activation of coagulation. It has been recently hypothesized that there may be two distinct sub-phenotypes in SCD: one where hemolysis and NO depletion predominates (hemolysis/endothelial dysfunction) and the other where vaso-occlusion and increased whole blood viscosity plays a more prominent role. The clinical complications of SCD thus cluster into one of the two subphenotypes: pulmonary hypertension, priapism, leg ulcers and stroke appear to be more commonly associated with the hemolysis/NO depletion/endothelial dysfunction subphenotype, whereas frequent pain episodes, acute chest syndrome, osteonecrosis and retinopathy tend to be more common in the viscosity/vaso-occlusion group. We had previously analyzed the records of 124 patients with Hb SS or S-b° thalassemia followed at the Medical College of Georgia Adult Sickle Cell Clinic to validate the clustering of disease complications into the aforementioned two sub-phenotypes and found no significant associations between phenotypes within each sub-group, as well as between phenotypes across the groups (all p values &gt;0.1). The following criteria were used to define complications: We have now extended our analyses to 203 patients with Hb SS or S-b° thalassemia (ages 12–60; 101 males, 102 females). We performed principal component analysis on the data from 203 patients. A total of 10 sub-phenotype variables were used in the analysis. The variables are VOE, ACS, retinopathy, gallstones, AVN, stroke, nephropathy, pulmonary hypertension, leg ulcers, and priapism. The individual factor map based on the first 2 principal components is shown below. Each dot represents a patient in the figure. If the hypothesis of two groups of sub-phenotypes were correct, we would see two clusters of patients. However, from this figure, there is no clear clustering of patients. We also plotted the sub-phenotype variables factor map based on the results from the principal components analysis. As shown in the following figure, the sub-phenotypes are not clustered into two groups as predicted by the hypothesis. In particular, we have retinopathy in one extreme and gallstones in the other. They are not clustered in one group. Our results indicate that the complications of sickle cell disease do not cluster into two distinct subphenotypes as previously hypothesized. While this hypothesis may provide a useful conceptual framework in deconstructing and understanding various pathophysiologic mechanisms operative in sickle cell disease, such clear cut distinction is not applicable in clinical practice. Disclosures: No relevant conflicts of interest to declare.

Clinical Characteristics Associated with Survival in Adult Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3229-3229
Author(s):  
Hany Elmariah ◽  
Melanie E. Garrett ◽  
Kenneth I. Ataga ◽  
Allison E Ashley-Koch ◽  
Marilyn J. Telen
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Survival Data ◽  
Conflicts Of Interest ◽  
Cox Proportional Hazards Model ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Cerebrovascular Events ◽  
Hydroxyurea Therapy

Abstract Abstract 3229 Background: Sickle cell disease (SCD) greatly decreases survival of affected patients, and significant advances will be necessary to decrease the gap in expected survival between SCD patients and non-affected individuals. We examined the relationship of clinical differences among SCD patients to survival, in order to gain greater understanding of major contributors to early mortality. Identification of such factors could guide development of therapeutic options. Methods: Survival data were obtained for 417 adult subjects previously enrolled in a study of clinical outcome modifying genes in SCD from Duke University Medical Center and the University of North Carolina at Chapel Hill. All subjects were ≥18 years at the time of enrollment and were followed for a mean of 7.9 years (range 2.3–10 years). At enrollment, a number of clinical parameters were collected, including hemoglobin (Hb) genotype (SS, SC, Sβ0 thalassemia, or Sβ+thalassemia), baseline laboratory values (Hb, WBC, platelets, reticulocytes, fetal Hb, LDH, MCV, proteinuria), comorbidities (cerebrovascular events, pulmonary hypertension, history of acute chest syndrome, avascular necrosis, priapism, and pain crises - defined as number of hospitalizations in the past 12 months, among others), and medication status (hydroxyurea, narcotics, and others). Levels of soluble adhesion molecules (sICAM, sVCAM, sE-selectin, sP-selectin), NT-proBNP, TNF-α, and interleukins-6, -8, and -10 were measured for a subset of 87 subjects. Regression analysis based on the Cox proportional hazards model was employed to determine the effect of clinical phenotypes on survival time using PROC PHREG in SAS v9.2 (SAS Systems, Cary, NC). All models were adjusted for gender and age at enrollment. Results: Mean age at enrollment was 34 years (range 18 to 84 years). The mean age at death was 45 years (range 24 to 86 years). Subjects with HbSβ0 had the worst prognosis (p=0.0001), followed by subjects with SS, SC, and Sβ+. Lower glomerular filtration rate (GFR, hazard ratio [HR]=1.087 per each ml/min decrease in GFR, p<0.0001), incidence of pain crises (HR=2.038, p=0.005), pulmonary hypertension (HR=2.269, p=0.005), cerebrovascular events (HR=1.875, p=0.008), proteinuria (HR=1.922, p=0.011), seizures (HR=2.138, p=0.012), short-acting narcotics use (HR=1.693, p=0.033) and TIAs (HR=2.407, p=0.043) were significantly associated with decreased survival. Lower baseline Hb was also associated with decreased survival (HR=1.259 per g/dl decrease, p=0.0047), but after controlling for GFR, was no longer significant (p=0.274). Additionally, increased NT-proBNP (HR=1.617, p=0.0004) and sVCAM-1 (HR=2.032, p=0.0003) were associated with decreased survival. Fifty percent of patients were on hydroxyurea therapy, which was not associated with a change in survival (p=0.503). Conclusion: SCD continues to reduce life expectancy for affected individuals, particularly those with Hb Sβ0 and SS. Surprisingly, we found that Sβ0 had a significantly worse survival compared to SS. Cerebrovascular events, pulmonary hypertension, proteinuria, decreased GFR, and more frequent pain crises were also strongly associated with poorer survival. Not only were these comorbidities individually associated with decreased survival, but an additive effect was observed, such that subjects with a greater number of negative endpoints had worse survival (p<0.0001). These traits may provide some utility in predicting prognosis of SCD patients. More importantly, aggressive management of these comorbidities may produce a survival benefit. The association of higher sVCAM-1 levels with decreased survival suggests that targeted therapies to reduce endothelial damage and inflammation may also be beneficial. In contrast to prior studies, hydroxyurea therapy had no influence on survival. This may reflect a failure in some patients to reach the maximum tolerated dose, lack of compliance, or more severe baseline disease in those patients who were treated. Disclosures: No relevant conflicts of interest to declare.

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