Patient‐focused inquiry on Hydroxyurea Therapy Adherence and Reasons for Discontinuation in Adults with Sickle Cell Disease

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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Overlapping Onset and Sequential Progression of Vasculopathy in Multiple Organs in Sickle Cell Disease

Blood ◽

10.1182/blood.v128.22.3660.3660 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3660-3660

Author(s):

Shruti Chaturvedi ◽

Djamila Ghafuri ◽

Adetola A. Kassim ◽

Michael DeBaun

Keyword(s):

Pulmonary Hypertension ◽

Magnetic Resonance ◽

Sickle Cell Disease ◽

Mortality Rate ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Age Of Onset ◽

Cell Disease ◽

Multiple Organs ◽

Hydroxyurea Therapy

Abstract Background: Sickle cell disease (SCD) is associated with vasculopathy in multiple vital organs, which ultimately leads to complications such as stroke, proliferative retinopathy, chronic kidney disease and pulmonary hypertension. Existing studies focus on single organ specific vasculopathy without an emphasis on shared mechanisms and simultaneous progression of vasculopathy in multiple organs. We conducted this retrospective cohort study to determine the onset and progression, as well as sequence of involvement of vasculopathy in the central nervous system (CNS), eye, kidney and lungs of adults with SCD. Methods: Our institutional practice is to perform annual magnetic resonance imaging with magnetic resonance angiography (MRI/MRA, for CNS vasculopathy and silent cerebral infarcts), echocardiography (for tricuspidregurgitant jet velocity > 2.5 m/sec, a surrogate of pulmonary hypertension), retinal examination, and measurement of urinaryalbumin:creatinine ratio, and serum creatinine in all adults with SCD. All patients were followed until death or last clinical encounter. Data were summarized as counts and proportions. Multivariable logistic regression was used to identify associations of number of organs affected with mortality. Results: We identified 280 adults with SCD followed for a median period of 66 months (interquartile range [IQR] 15.7 to 112 months). Median age was 31.1 (IQR 25.4 to 39.7) years and 49.6% were female. Over half (51.8%) were on hydroxyurea therapy. The prevalence of vasculopathy in different organs was: CNS, 37.8%; retinopathy 26.1%, proteinuria, 20.7% (nephropathy 5.71%); and pulmonary hypertension, 15.36%. There was no evidence of vasculopathy in 103 (36.8%) individuals. Of the remaining 177 (63.2%) adults, vasculopathy was present in one, two, three and all four end organs in100, 55, 18, and 4 individuals respectively. Median age of onset was earliest for CNS vasculopathy [25.42 (IQR 19.31, 38.85)] years followed by retinopathy [28.41 (IQR 23.04, 35.79)] years, proteinuria [31.25 (IQR 25.6, 46.0)] years, and pulmonary hypertension [33.08 (IQR 23.83, 47.17)] years (Figure 1). Mortality rate was 1.69 per 100 patient-years. Patients with vasculopathy affecting 3 or 4 organs had a significantly higher mortality rate than those with 0-2 organs affected by vasculopathy [odds ratio 5.50 (95%CI 4.49-20.35), p=0.007], adjusted for phenotype, age, sex, hydroxyurea therapy, and smoking status. Conclusion: Vasculopathy in SCD occurs in multiple organs simultaneously, with a predisposition to affectthe CNS first. These data strongly support that multiple vasculopathy is common, and when present in at least three organs, is associated with earlier mortality. Disclosures No relevant conflicts of interest to declare.

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Higher Nocturnal and Awake Oxygen Saturations in Children with Sickle Cell Disease Receiving Hydroxyurea Therapy

Annals of the American Thoracic Society ◽

10.1513/annalsats.201410-473oc ◽

2015 ◽

Vol 12 (7) ◽

pp. 1044-1049 ◽

Cited By ~ 16

Author(s):

Indra Narang ◽

Gili Kadmon ◽

Dennison Lai ◽

Simranpal Dhanju ◽

Melanie Kirby-Allen ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Hydroxyurea Therapy

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CLINICAL AND HEMATOLOGICAL EFFECTS OF HYDROXYUREA THERAPY IN MANAGEMENT OF SICKLE CELL ANEMIA

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v3i7.383 ◽

2019 ◽

Vol 3 (7) ◽

Author(s):

Dr. Rajesh Shukla ◽

Dr. Mehul Gajera

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Hospital Admissions ◽

White Blood Cells ◽

Sub Saharan Africa ◽

P Value ◽

Cell Disease ◽

Hematological Effects ◽

Sub Saharan ◽

Hydroxyurea Therapy

Background: The most predominant form of haemoglobinopathy worldwide is sickle cell disease. The greatest burden of the disease lies in sub-Saharan Africa and Asia5. Objective: To evaluate the effectiveness of HU therapy in sickle cell disease as measured by decrease in crises rate, hospital admissions, days of hospitalization and number of blood transfusions. Methods: the study was conducted on 79 children of 1-16 year age. Out of which in only 75 patients Hydroxyurea therapy was started as they were found to be eligible. 16% of the patients responded to 15 mg/kg/ day of HU, 50.66% responded to 20 mg/kg/ day, 29.33% to 25 mg/kg/ day and only 4% needed a dose escalation to 30 mg/kg/ day for the response. Results: Our study showed a significant reduction in the VOC rate from 243 episodes to 46 episodes (p value <0.001), the number of ACS reduced from 37 episodes to 5 episodes (p value <0.001), also there is a significant decline in the rates of hemolytic crises from 63 episodes to 10 episodes per year, Significant increase in the HbF levels from 15.87±5.50% to 21.77.±4.06% (p value <0.001). There was a definite and significant reduction in the number of hospitalization days from 7.76±4.76 to 3.79±2.29 days and in the number of admissions per year dropped significantly from 4.80 ± 1.41 to 1.42± 0.61 per year. Conclusion: Hydroxyurea reduced the frequency of painful crises and diminished the number of hospitalization, transfusion, and episodes of acute chest syndrome17. Keywords: Haemoglobin (Hb), Hydroxyurea (HU), Mean Corpuscular Volume (MCV), Pletelet Counts, Sickle Cell Disease (SCD), White Blood Cells (WBC).

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