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.

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.

Combining Fetal Hemoglobin and Reticulocytosis to Index Clinical Severity of Sickle Cell Disease in Children.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2556-2556
Author(s):  
Emily Riehm Meier ◽  
Colleen Byrnes ◽  
Maxine Weissman ◽  
Pierre Noel ◽  
Naomi L.C. Luban ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Supportive Care ◽  
Disease Severity ◽  
Sickle Cell ◽  
Fetal Hemoglobin ◽  
Treatment Decisions ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
F Cells

Abstract Abstract 2556 Poster Board II-533 Predictors of disease severity during infancy or childhood in patients with sickle cell disease (SCD) are needed to guide treatment decisions with therapies that have known toxicities [transfusion, hydroxyurea (HU), bone marrow transplant]. Erythrocyte fetal hemoglobin (HbF) expression levels above 20% reduce sickle hemoglobin (HbS) polymerization and decrease hemolysis. As a result of the decreased hemolysis, the survival of erythrocytes is prolonged, and the overall level of erythropoiesis is reduced. To determine if clinical markers of increased HbF production and decreased erythropoiesis may be combined to score disease severity, we developed a Fetal Hemoglobin-Reticulocytosis Index (FRI) defined as: [HbF (%) × non-transfused F-cells (%)] / [Absolute Reticulocyte Count (K/uL)]. For these studies, red cell lysates were analyzed by high power liquid chromatography (HPLC) to estimate HbA, HbS, and HbF fractions. F-cells were analyzed by flow cytometry using antibodies directed against HbF, while transfused cells were labeled with antibodies directed against HbA. Dual staining with both antibodies provided a method for accurately distinguishing transfused and non-transfused F-cells (NT F-cells). A minimum of 10,000 cells was analyzed in all samples. Absolute reticulocyte counts (ARC) were determined using a Sysmex XE 2100 hematology analyzer (Sysmex America, Mundelein, IL). Preliminary studies revealed FRI values near 100 at one month of age followed by a rapid drop before the age of 4 years. Blood from children between the ages of 4 and 21 years was also studied to determine if FRI correlates with therapeutic regimen. FRI values for three groups were compared: those treated with chronic transfusion (n=19, mean FRI=0.72±1.04), HU (n=19, mean FRI=5.61±6.24), versus supportive care alone that did not include recent transfusions (n=42, mean FRI=2.70 ±4.85). When the FRI values from each of these groups were placed in rank order, the slope of the line increased sharply from a linear to an exponential shape near the FRI value of 2. To determine if the FRI=2 inflection may be indicative of reduced disease severity, the number of SCD events were determined in the 42 study subjects treated with supportive care. Overall, twenty-eight (66.7%) patients had an FRI<2, and fourteen (33.3%) patients had an FRI≥2. Among those patients, SCD events were tallied (listed in descending order according to number of events): painful crises requiring hospitalization (FRI<2, n=128; FRI≥2, n=25), pneumonia /acute chest syndrome (FRI<2, n=74; FRI≥2, n=18), splenic sequestration (FRI<2, n=14; FRI≥2, n=0), conditional transcranial Doppler [(TCD), FRI<2, n=13; FRI≥2, n=1), silent stroke (FRI<2, n=4; FRI≥2, n=2), bacteremia (FRI<2, n=2; FRI≥2, n=1), cholecystectomy (FRI<2, n=3; FRI≥2, n=0), and nephropathy (FRI<2, n=1; FRI≥2, n=0). None of the supportive care group had an overt stroke, abnormal TCD, sickle cell retinopathy, or priapism. Age adjusted analysis showed that the FRI≥2 group had significantly fewer total events per year [events/year: FRI<2 (0.70±0.52) vs. FRI≥2 (0.38 ± 0.36), p=0.02]. These data suggest that combining the clinical parameters of fetal hemoglobin production and reticulocytosis provides a simple index for SCD severity. Based upon this retrospective data, prospective studies are underway to determine if the FRI decline during infancy or FRI levels in childhood are useful to predict clinical severity and treatment decisions in SCD patients. Disclosures: No relevant conflicts of interest to declare.

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) &gt; 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 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.

scholarly journals Priapism in Sickle Cell Anemia: Emerging Mechanistic Understanding and Better Preventative Strategies

Anemia ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Genevieve M. Crane ◽  
Nelson E. Bennett
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Treatment Strategies ◽  
Vascular Complications ◽  
Cell Disease ◽  
Nitric Oxide Signaling ◽  
Risk Of Death ◽  
Ischemic Priapism

Sickle cell anemia is a common and disabling disorder profoundly affecting mortality as well as quality of life. Up to 35% of men with sickle cell disease are affected by painful, prolonged erections termed ischemic priapism. A priapic episode may result in fibrosis and permanent erectile dysfunction. The severity of sickle cell disease manifestations is variable dependent on a number of contributing genetic factors; however, priapism tends to cluster with other severe vascular complications including pulmonary hypertension, leg ulceration, and overall risk of death. The mechanisms underlying priapism in sickle cell disease have begun to be elucidated including hemolysis-mediated dysregulation of the nitric oxide signaling pathway and dysregulation of adenosine-mediated vasodilation. A better understanding of these mechanisms is leading toward novel preventative strategies. This paper will focus on the mechanisms underlying development of ischemic priapism in sickle cell disease, current acute and preventative treatment strategies, and future directions for improved management of this disorder.

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.

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.

Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4767-4767
Author(s):  
Giovanna Graziadei ◽  
Alessia Marcon ◽  
Martina Soldarini ◽  
Ilaria Gandolfi ◽  
Luisa Ronzoni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Clinical Complications ◽  
Significant Difference ◽  
The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

scholarly journals Cardiopulmonary Complications of Sickle Cell Disease: Role of Nitric Oxide and Hemolytic Anemia

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Mark T. Gladwin ◽  
Gregory J. Kato
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Iron Chelation ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Inflammatory Stress ◽  
Risk Of Death ◽  
Cardiopulmonary Complications

Abstract Medical advances in the management of patients with sickle cell disease, thalassemia, and other hemolytic anemias have led to significant increases in life expectancy. Improved public health, neonatal screening, parental and patient education, advances in red cell transfusion medicine, iron chelation therapy, penicillin prophylaxis for children, pneumococcal immunization, and hydroxyurea therapy have all likely contributed to this effect on longevity.1,2 Importantly, as a generation of patients with sickle cell disease and thalassemia ages, new chronic complications of these hemoglobinopathies develop. In this context, pulmonary hypertension is emerging as one of the leading causes of morbidity and mortality in adult sickle cell and thalassemia patients, and likely in patients with other hemolytic anemias. A common feature of both sickle cell disease and thalassemia is intravascular hemolysis and chronic anemia. Recent data suggest that chronic intravascular hemolysis is associated with a state of endothelial dysfunction characterized by reduced nitric oxide (NO) bioavailability, pro-oxidant and pro-inflammatory stress and coagulopathy, leading to vasomotor instability and ultimately producing a proliferative vasculopathy, a hallmark of which is the development of pulmonary hypertension in adulthood.3–5 In conclusion, pulmonary hypertension is common in patients with hereditary hemolytic anemias and is associated with a high risk of death in patients with sickle cell disease. New therapies targeting this vasculopathy and aimed at normalizing the vasodilator:vasoconstrictor balance are discussed.

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