N-Terminal Natriuretic Peptide and Ventilation-Perfusion Lung Scan in Sickle Cell Disease and Thalassemia Patients with Pulmonary Hypertension

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 β-thalassemia major (β-TM) and 15 β-thalassemia intermedia (β-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 ± 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, β-TI and β-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.     

Hemodynamic characteristics and predictors of pulmonary hypertension in patients with sickle cell disease

Pulmonary hypertension is a common co-morbidity of sickle cell disease with an associated increased mortality risk, but its etiology is not well-understood. To evaluate the hemodynamic characteristics, clinical predictors, and cardiovascular manifestations of elevated pulmonary arterial pressure in this population, we performed noninvasive hemodynamic assessments of 135 patients with sickle cell disease using Doppler echocardiography. A diagnosis of pulmonary hypertension was determined by gender-, age-, and body mass index-specific normal reference ranges for tricuspid regurgitation jet velocities (TRVs). A high TRV was noted in 34 patients (25%). Pulmonary vascular resistance was elevated in only 2 (6%) of the 34 patients with suspected pulmonary hypertension but was significantly greater than in those with normal TRV. On univariate regression, the TRV correlated with age, body mass index, left atrial pressure, and right ventricular stroke volume and was negatively associated with hemoglobin and glomerular filtration rate. The left atrial pressure, right ventricular stroke volume, and hemoglobin remained independent predictors of TRV in a multivariate model. A greater TRV was also associated with larger right ventricular and right atrial chamber sizes and greater N-terminal probrain natriuretic peptide levels. In conclusion, our results suggest that the mild elevation in TRV often observed in patients with sickle cell disease is rarely associated with a high pulmonary vascular resistance and that multiple factors-including the compensatory high output state associated with anemia, pulmonary venous hypertension, and pulmonary vasculopathy-can contribute to an elevated pulmonary arterial pressure in these patients.     

Determinants of right ventricular pressure in mild hypertension.

OBJECTIVE : Doppler echocardiography was used to define reference values and determinants of tricuspid regurgitation peak velocity (TRV) in hypertensive patients. A TRV value > 2.5 m/s is the threshold usually defining abnormal right ventricular systolic pressure. DESIGN AND PATIENTS : Doppler echocardiography was performed in 320 consecutive uncomplicated hypertensive patients, without overt pulmonary or heart disease. Doppler echocardiography included LV mass measurement, LV inflow and pulmonary venous flow analysis, LV systolic function and TRV measurements. RESULTS : Among 320 patients, 255 had normal TRV < 2.5 m/s and 65 had elevated TRV > or = 2.5 m/s. Compared with the normal TRV group, the elevated TRV group was older (60 versus 50 years, P < 0.0001), systolic blood pressure was higher (156 versus 151 mmHg, P = 0.02) and antihypertensive therapy was more frequent (68 versus 51%, P = 0.02); indexed LV mass was higher (45.4 versus 40.6 g/m2.7, P = 0.001), pulmonary D wave peak velocity was higher (42 versus 38 cm/s, P = 0.03). In univariate analysis, age was the most predictive variable of TRV (r = 0.36). In multivariate analysis, three variables were independently related to TRV: age, LV mass, pulmonary D wave (multiple r = 0.47). CONCLUSION : In mild hypertension, TRV is independently related to age, and to a lesser extent, to LV morphology and LV filling pressure. In clinical practice, age should be taken into account to interpret TRV.     

Relative systemic hypertension in patients with sickle cell disease is associated with risk of pulmonary hypertension and renal insufficiency

We analyzed entry data from 163 adult hemoglobin SS and Sbeta(0) thalassemia patients enrolled in the prospective Sickle Cell Pulmonary Hypertension Screening Study and stratified their ECHO-determined tricuspid regurgitant jet velocity (TRV) and serum creatinine concentration according to three systemic blood pressure categories. TRV was >or= 2.5 m/sec in 27% of the patients with systolic blood pressure (SBP) <120 mmHg and diastolic blood pressure (DBP) <70 mmHg, in 37% with SBP 120-139 mmHg or DBP 70-89 mmHg, and in 93% with SBP 140 mmHg or DBP 90 mmHg or higher (P<0.0005 for trend). Serum creatinine concentration was 1.0 mg/dL or higher in 7% of patients with SBP <120 mmHg and DBP <70 mmHg, in 17% with SBP 120-139 mmHg or DBP 70-89 mmHg and 50% with SBP 140 mmHg or DBP 90 mmHg or higher (P<0.0005 for trend). Over 2 years of follow-up, there were trends for more frequent progression to elevated TRV (P=0.073) or creatinine (P=0.037) values according to the higher systemic blood pressure categories. Our findings suggest that systemic SBP 120-139 mmHg or DBP 70-89 mmHg defines a category of relative systemic hypertension in patients with sickle cell disease that is associated with increased risk for pulmonary hypertension and renal dysfunction. Whether antihypertensive and/or nitric oxide donor therapy in sickle cell disease patients with relative hypertension prevents these and other complications should be determined by clinical trials.     

Cardiac manifestations in sickle cell disease varies with patient genotype

Cardiac involvement is well characterized in sickle cell anaemia (SCA) but cardiac features associated with Haemoglobin SC (HbSC) disease are mostly unknown. We compared 60 patients with HbSC disease (median age 31 years, 25 men) to 60 SCA patients and 60 controls matched for age and gender. Left ventricular ejection fraction (LVEF), left ventricle (LV) mass index (LVMi), cardiac index and peak tricuspid regurgitation velocity (TRV) were measured using echocardiography. LV filling pressures were assessed using the ratio of early diastolic transmitral velocity to tissue velocity (E/e’ ratio). The LVMi was higher in both genotypes compared to controls. However, whereas LV hypertrophy was observed only in 3(5%) HbSC patients, this condition was diagnosed in 27(45%) SCA patients (P < 0·0001). While cardiac index and TRV were similar in HbSC compared to controls, SCA patients exhibited elevated cardiac output and TRV. LVEF was similar in the 3 groups. However, both genotypes had a higher E/e’ ratio compared to controls. Cardiac involvement in SCA was related to anaemia and haemolysis, while LV diastolic dysfunction and TRV in HbSC disease patients were related to arterial hypertension and overweight comorbidities. In summary, cardiac involvement and its determinants are different in HbSC disease and SCA. Patient's genotype should be considered with regard to the echocardiographic indications and findings.     

Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity

In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity. A TRV ≥ 2.7 m/s and a 6-minute walk distance (6MWD) between 150 and 500 m were required for enrollment in this 16-week, double-blind, placebo-controlled sildenafil trial. After 74 of the screened subjects were randomized, the study was stopped early due to a higher percentage of subjects experiencing serious adverse events in the sildenafil arm (45% of sildenafil, 22% of placebo, P = .022). Subject hospitalization for pain was the predominant cause for this difference: 35% with sildenafil compared with 14% with placebo (P = .029). There was no evidence of a treatment effect on 6MWD (placebo-corrected effect -9 m; 95% confidence interval [95% CI] -56-38; P = .703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531.     

The association between tricuspid regurgitation velocity and 5‐year survival in a North West London population of patients with sickle cell disease in the United Kingdom

Raised tricuspid regurgitant velocity (TRV) occurs in approximately 30% of adults with sickle cell disease (SCD), and has been shown to be an independent risk factor for death. TRV was assessed in 164 SCD patients who were subsequently followed up for survival. Raised pulmonary pressures were defined as a TRV jet ≥2·5 m/s on echocardiography. Elevated TRV was present in 29·1% of patients and it was associated with increased age and left atrial diameter. There were 15 deaths (9·1%) over a median of 68·1 months follow up; seven patients had increased TRV, and eight patients had a TRV<2·5 m/s. Higher TRV values were associated with a greater than 4‐fold increased risk of death (Hazard Ratio: 4·48, 99% confidence interval 1·01‐19·8), although we found a lower overall mortality rate than has been reported in previous studies. TRV was not an independent risk factor for death. We have confirmed the association between raised TRV and mortality in a UK SCD population whose disease severity appears to be less than that reported in previous studies. Further prospective studies are needed to more clearly characterize which patient factors modify survival in SCD patients with raised TRV.     

Echocardiographic Estimation of Pulmonary Vascular Resistance in Chronic Thromboembolic Pulmonary Hypertension: Utility of Right Heart Doppler Measurements

The ratio of tricuspid regurgitation velocity divided by the velocity‐time integral of right ventricular outflow tract pulsed‐wave Doppler tracing (TRV/VTI_RVOT) has been used to estimate pulmonary vascular resistance (PVR). However, this method has not been validated in chronic thromboembolic pulmonary hypertension (CTEPH). We assessed the utility of TRV/VTI_RVOT in patients with CTEPH and PVR from 2 to 20 WU. All had right heart catheterization (RHC) within 2 days of echocardiography. TRV/VTI_RVOT was calculated and RHC‐derived pressures, PVR, and cardiac outputs were recorded. Mean pulmonary artery pressure was 47 ± 12 mmHg, cardiac output: 4.2 ± 1.1 L/min, PVR: 9 ± 4 WU, right atrial pressure: 12 ± 6 mmHg. Mean VTI_RVOT was 13 ± 5 cm; mean TRV was 4.2 ± 0.8 m/s, mean tricuspid regurgitation severity was 2.5 ± 0.8 (1 = trace, 2 = mild, 3 = moderate, 4 = severe). Regression analysis demonstrated a correlation between RHC PVR and TRV/VTI_RVOT: PVR = 19.4 × (TRV/VTI_RVOT) + 2.4 (r = 0.74, P < 0.001). However, Bland–Altman analysis found a poor degree of agreement between echo‐derived PVR and RHC PVR. We also studied 28 patients with non‐CTEPH pulmonary hypertension. Similar analysis revealed a regression equation of PVR = 20.1 × (TRV/VTI_RVOT) + 0.3 (r = 0.57, P < 0.01). Conclusion: TRV/VTI_RVOT is only marginally useful for estimating PVR in CTEPH (r = 0.74). Moreover, the regression equation in CTEPH differs significantly from previous studies in pulmonary hypertension. Reasons for this may include the markedly elevated PVR levels in this population and specific effects on VTI_RVOT from CTEPH.     

Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report

An elevated tricuspid regurgitant jet velocity (TRV) is associated with hemolysis and early mortality in sickle cell disease, yet risk factors, clinical parameters, and mortality associated with this biomarker in thalassemia are poorly defined. This report summarizes the prevalence of an elevated TRV in 325 patients screened by Doppler echocardiography in the Thalassemia Clinical Research Network. A documented TRV was reported in 148 of 325 (46%) of patients. Average age was 25.9 years (range, 5-56 years) and 97% were transfusion-dependent. Mean TRV was 2.3 ± 0.4 m/s (range, 0.2-3.5 m/s). An abnormal TRV ≥ 2.5 m/s was identified in 49 of 148 (33%) of patients with a documented TRV, 5% (8/148), with a TRV ≥ 3.0 m/s, suggesting significant PH risk. Older age was strongly associated with a high TRV; however, 16% of children had a TRV ≥ 2.5 m/s. A history of splenectomy, hepatitis C, smoking, or high white blood cell count was associated with TRV elevation. In summary, an elevated TRV is noted in one-third of transfusion-dependent thalassemia patients with a documented value and develops in both children and adults. Age, splenectomy, hepatitis C, and smoking are significant univariate risk factors, with splenectomy surfacing as the dominant risk factor over time. Mortality was low in this cohort. Prospective longitudinal studies are needed. This study is registered at http://www.clinicaltrials.gov as NCT00661804.     

Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension.

OBJECTIVES: The aim of this study was to explore the full range of tricuspid valve regurgitation velocity (TRV) at rest and with exercise in disease free individuals. Additionally we examined the relationship of stroke volume (SV), cardiac output (CO) and TRV to exercise capacity. BACKGROUND: Doppler evaluation of TRV can be used to estimate pulmonary artery systolic pressure (PASP). Most studies have assumed TRV < or = 2.5 m/s as the upper limits of normal. The full range of TRV with exercise has been incompletely defined. METHODS: Highly conditioned athletes (n = 26) and healthy, active, young male volunteers (n = 14) underwent standardized recumbent bicycle exercise. Exercise parameters included: TRV, SV, CO, systolic (SBP) and diastolic (DBP) systemic blood pressure. RESULTS: Tricuspid valve regurgitation, SV, HR and CO were significantly higher in athletes than in nonathletes over all workloads, including rest. Systolic blood pressure and DBP did not show significant differences between the two groups. CONCLUSIONS: This study defines the upper physiologic limits of TRV at rest and during exercise in normals and provides a noninvasive standard for the diagnosis of pulmonary hypertension.     

Tricuspid regurgitant jet velocity is associated with hemolysis in children and young adults with sickle cell disease evaluated for pulmonary hypertension

Tricuspid regurgitant jet velocity (TRJV) >or= 2.5 m/sec. on echocardiography is a surrogate marker for pulmonary hypertension (PHT) in adults with sickle cell disease (SCD). We prospectively examined the relationship between TRJV and laboratory markers of hemolysis in 51 children and young adults with SCD at baseline. We found significant correlations between TRJV and lactate dehydrogenase (LDH), hemoglobin (Hb), reticulocyte count (retic) and aspartate aminotransferase (AST). LDH, retic and AST were significantly higher and Hb was lower in subjects with TRJV >or= 2.5 m/sec. We conclude that hemolysis significantly contributes to TRJV elevation in children and young adults with SCD.     

Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease?

Pulmonary hypertension is a life-threatening complication of sickle cell disease. L-Arginine is the nitrogen donor for synthesis of nitric oxide, a potent vasodilator that is deficient during times of sickle cell crisis. This deficiency may play a role in pulmonary hypertension. The enzyme arginase hydrolyzes arginine to ornithine and urea, and thus, it may compete with nitric oxide synthase, leading to decreased nitric oxide production. Nitric oxide therapy by inhalation has improved pulmonary hypertension associated with acute chest syndrome in sickle cell disease, and several studies demonstrate therapeutic benefits of arginine therapy for primary and secondary pulmonary hypertension. We sought to determine the effects of arginine therapy on pulmonary hypertension in patients with sickle cell disease. Arginase activity was also determined. Oral arginine produced a 15.2% mean reduction in estimated pulmonary artery systolic pressure (63.9 +/- 13 to 54.2 +/- 12 mm Hg, p = 0.002) after 5 days of therapy in 10 patients. Arginase activity was elevated almost twofold (p = 0.07) in patients with pulmonary hypertension and may limit arginine bioavailability. With limited treatment options and a high mortality rate for patients with sickle cell disease who develop pulmonary hypertension, arginine is a promising new therapy that warrants further investigation.     

Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension

Pulmonary hypertension is a frequent complication of sickle cell disease that is associated with haemolysis, impaired nitric oxide bioavailability and high mortality. We sought to evaluate the safety and efficacy of selective pulmonary vasodilators and antiproliferative agents in this at-risk population. After optimising sickle cell disease therapy to stabilise haemoglobin and fetal haemoglobin levels, we evaluated the safety and efficacy of sildenafil in 12 patients with sickle cell disease and pulmonary hypertension. Sildenafil therapy (mean duration 6 +/- 1 months) decreased the estimated pulmonary artery systolic pressure [50 +/- 4 to 41 +/- 3 mmHg; difference 9 mmHg, 95% confidence interval (CI): 0.3-17, P = 0.043] and increased the 6-min walk distance (384 +/- 30 to 462 +/- 28 m; difference 78 m, 95% CI: 40-117, P = 0.0012). Transient headaches occurred in two patients and transient eye-lid oedema in four patients. No episodes of priapism occurred in the three men in the study; two of them were on chronic exchange transfusions and one had erectile dysfunction. In conclusion: (1) sickle cell disease patients with anaemia and pulmonary hypertension have significant exercise limitation; (2) the 6-min walk distance may be a valid endpoint in this population; (3) therapy with sildenafil appears safe and improves pulmonary hypertension and exercise capacity. Additional phase I studies in males with sickle cell disease followed by phase II/III placebo controlled trials evaluating the safety and efficacy of sildenafil therapy in sickle cell disease patients with pulmonary hypertension are warranted.     

Longitudinal study of echocardiography‐derived tricuspid regurgitant jet velocity in sickle cell disease

Although echocardiography‐derived tricuspid regurgitant jet velocity (TRV) is associated with increased mortality in sickle cell disease (SCD), its rate of increase and predictive markers of its progression are unknown. We evaluated 55 subjects (median age: 38 years, range: 20–65 years) with at least two measurable TRVs, followed for a median of 4·5 years (range: 1·0–10·5 years) in a single‐centre, prospective study. Thirty‐one subjects (56%) showed an increase in TRV, while 24 subjects (44%) showed no change or a decrease in TRV. A linear mixed effects model indicated an overall rate of increase in the TRV of 0·02 m/s per year (P = 0·023). The model showed that treatment with hydroxycarbamide was associated with an initial TRV that was 0·20 m/s lower than no such treatment (P = 0·033), while treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers was associated with an increase in the TRV (P = 0·006). In summary, although some patients have clinically meaningful increases, the overall rate of TRV increase is slow. Treatment with hydroxycarbamide may decrease the progression of TRV. Additional studies are required to determine the optimal frequency of screening echocardiography and the effect of therapeutic interventions on the progression of TRV in SCD.     

Elevated tricuspid regurgitant jet velocity in subgroups of thalassemia patients: insight into pathophysiology and the effect of splenectomy

A high tricuspid regurgitant jet velocity (TRV) signifies a risk for or established pulmonary hypertension (PH), which is a serious complication in thalassemia patients. The underlying pathophysiology in thalassemia subgroups and potential biomarkers for early detection and monitoring are not well defined, in particular as they relate to spleen removal. To better understand some of these unresolved aspects, we examined 76 thalassemia patients (35 non-transfused), 25 splenectomized non-thalassemia patients (15 with hereditary spherocytosis), and 12 healthy controls. An elevated TRV (>2.5 m/s) was found in 25/76 (33 %) of the patients, confined to non-transfused or those with a late start of transfusions, including patients with hemoglobin H-constant spring, a finding not previously described. These non or late-transfused patients (76 % splenectomized) had significantly increased platelet activation (sCD40L), high platelet count, endothelial activation (endothelin-1), and hemolysis (LDH, plasma-free Hb), while hypercoagulable and inflammatory markers were not significantly increased. The same markers were increased in the seven patients with confirmed PH on cardiac catheterization, suggesting their possible role for screening patients at risk for PH. A combination of hemolysis and absence of spleen is necessary for developing a high TRV, as neither chronic hemolysis in the non-splenectomized thalassemia patients nor splenectomy without hemolysis, in the non-thalassemia patients, resulted in an increase in TRV.     

Hemolytic anemia-associated pulmonary hypertension in sickle cell disease

Pulmonary hypertension is one of the leading causes of death in adult sickle cell patients, with a prevalence of 20% to 40%. Although these patients have lower pulmonary pressures than patients with primary pulmonary hypertension, both groups suffer high 2-year mortality rates. Pulmonary hypertension may go undetected until the disease is advanced. Therefore, all adult patients with sickle cell disease should be screened with transthoracic Doppler echocardiogram and the tricuspid regurgitant jet (TRJ) velocity measured to estimate pulmonary artery pressures. A regurgitant jet (RJ) velocity of 2.5 m/s or higher establishes diagnosis and suggests a high risk of death (rate ratio of 10.1; CI= 2.2-47). Basic and epidemiologic studies suggest that pulmonary hypertension in sickle cell disease is mechanistically linked to chronic hemolytic anemia. Hemolysis results in the release of hemoglobin and arginase from the erythrocyte, increasing the consumption and decreasing the production of nitric oxide (NO), respectively. NO is a critical regulator of vasodilation and vascular homeostasis whose inactivation produces vasoconstriction and proliferative vasculopathy. Finally, we review suggested therapies including the established treatments and new pulmonary vasodilator and remodeling agents in the management of pulmonary hypertension in hemolytic anemias.     

NT‐proBNP as a marker of cardiopulmonary status in sickle cell anaemia in Africa

N‐terminal (NT) pro‐brain natriuretic peptide (proBNP) ≥160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross‐sectional study at Ahmadu Bello University Teaching Hospital, Shika‐Zaria, Nigeria, we studied 133 hydroxycarbamide‐naïve Nigerian sickle cell anaemia patients aged 18–52 years at steady‐state and 65 healthy controls. Twenty‐six percent of patients versus 5% of controls had NT‐proBNP ≥160 ng/l (P = 0·0006). By logistic regression among the patients, human immunodeficiency virus seropositivity, higher serum ferritin and lower haemoglobin or higher lactate dehydrogenase independently predicted elevated NT‐proBNP. After adjustment for haemoglobin concentration, elevated NT‐proBNP concentration was associated with an estimated 7·8‐fold increase in the odds of severe functional impairment, defined as an inability to walk more than 300 m in 6 min (95% confidence interval 1·5–32·6; P = 0·005). Similarly, elevated tricuspid regurgitation velocity was associated with an estimated 5·6‐fold increase in the odds of functional impairment (95% confidence interval 1·5–21·0; P = 0·011). In conclusion, NT‐proBNP elevation is common and is associated with markers of anaemia, inflammation and iron status and with severe functional impairment among sickle cell anaemia patients in Nigeria.     

Prospective evaluation of chronic organ damage in adult sickle cell patients: A seven‐year follow‐up study

Organ damage in sickle cell disease (SCD) is a crucial determinant for disease severity and prognosis. In a previous study, we analyzed the prevalence of SCD‐related organ damage and complications in adult sickle cell patients. We now describe a seven‐year follow‐up of this cohort.All patients from the primary analysis in 2006 (n = 104), were included for follow‐up. Patients were screened for SCD‐related organ damage and complications (microalbuminuria, renal failure, elevated tricuspid regurgitation flow velocity (TRV) (≥2.5 m/seconds), retinopathy, iron overload, cholelithiasis, avascular osteonecrosis, leg ulcers, acute chest syndrome (ACS), stroke, priapism and admissions for vaso‐occlusive crises (VOC) biannually. Upon 7 years of follow‐up, progression in the prevalence of avascular osteonecrosis (from 12.5% to 20.4%), renal failure (from 6.7% to 23.4%), retinopathy (from 39.7% to 53.8%) was observed in the whole group. In HbSS/HbSβ⁰‐thal patients also progression in microalbuminuria (from 34% to 45%) and elevated TRV (from 40% to 48%) was observed while hardly any progression in the prevalence of cholelithiasis, priapism, stroke or chronic ulcers was seen. The proportion of patients with at least one episode of ACS increased in the group of HbSS/HbSβ⁰‐thal patients from 32% to 49.1%. In conclusion, 62% of the sickle cell patients in this prospective cohort study developed a new SCD‐related complication in a comprehensive care setting within 7 years of follow‐up. Although the hospital admission rate for VOC remained stable, multiple forms of organ damage increased substantially. These observations underline the need for continued screening for organ damage in all adult patients with SCD.