Clustering of end‐organ disease and earlier mortality in adults with sickle cell disease: A retrospective‐prospective cohort study

Abstract

Chronic end-organ complications result in morbidity and mortality in adults with sickle cell disease (SCD). In a retrospective-prospective cohort of 150 adults with SCD who received standard care screening for pulmonary function abnormalities, cardiac disease, and renal assessment from January 2003 to 2016, we tested the hypothesis that clustering of end-organ disease is common and multiple organ impairment predicts mortality. Any end-organ disease occurred in 59.3% of individuals, and 24.0% developed multiple organ (>1) end-organ disease. The number of end-organs affected was associated with mortality (P ≤ .001); 8.2% (5 of 61) of individuals with no affected end-organ, 9.4% (5 of 53) of those with 1 affected organ, 20.7% (6 of 29) of those with 2 affected end-organs, and 85.7% (6 of 7) with 3 affected end-organs died over a median follow up period of 8.7 (interquartile range 3.5-11.4) years. Of the 22 individuals who died, 77.3% had evidence of any SCD-related end-organ impairment, and this was the primary or secondary cause of death in 45.0%. SCD-related chronic impairment in multiple organs, and its association with mortality, highlights the need to understand the common mechanisms underlying chronic end-organ damage in SCD, and the urgent need to develop interventions to prevent irreversible end-organ complications in SCD.

Low hemoglobin increases risk for cerebrovascular disease, kidney disease, pulmonary vasculopathy, and mortality in sickle cell disease: A systematic literature review and meta-analysis

“…Although most patients with SCD in resource-rich countries live beyond childhood, the median life expectancy remains low, and is reduced by 2 to 3 decades [8]. This increased risk of early mortality is, in large part, due to the development of multiple end-organ damage [9][10][11][12].…”

Validation of a composite vascular high‐risk profile for adult patients with sickle cell disease

“…As patients with SCD grow older, they develop end-organ damage related to vascular complications, including pulmonary hypertension, diastolic left heart disease, and nephropathy. 1 More than 50% of adult patients have dysfunction of at least one organ system, and 25% have multi-organ dysfunction. Simultaneous endorgan disease in heart, lung and kidney increased mortality by approximately 4-fold.…”

“…Simultaneous endorgan disease in heart, lung and kidney increased mortality by approximately 4-fold. 1 Intravascular hemolysis contributes to pulmonary vasculopathy and renal insufficiency by elaboration of free hemoglobin, which produces redox stress, inflammation, hypercoagulability, and vascular injury. 2 We have reported that elevated tricuspid regurgitation velocity (TRV), a non-invasive marker of elevated systolic pulmonary artery pressure, is associated with an increased risk of death in two independent cohorts.…”

“…Survival was significantly lower in high-risk group (HR = 5.38, 95%CI = 3.20-9.04)Driver mutation-specific clinical and genomic correlates differ between primary and secondary myelofibrosisTo the Editor:Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) that has evolved from a prior diagnosis of polycythemia (PV) or essential thrombocythemia (ET) are myeloproliferative neoplasms (MPNs) characterized by the presence of a phenotypic driver mutation in one of three genes: Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), and calreticulin (CALR). More than 90% of patients will exhibit a mutation in one of these three genes, with the remaining patients being deemed to have "triple-negative" (TN) disease 1. Pathogenic mutations in JAK2, MPL, and CALR invariably lead to upregulation of JAK/signal transducer and activator of transcription (STAT) signaling and a heterogeneous clinical phenotype that often features dysfunctional hematopoiesis, constitutional symptoms, extramedullary hematopoiesis, and an increased propensity to develop acute myeloid leukemia (AML) 1.…”

“…More than 90% of patients will exhibit a mutation in one of these three genes, with the remaining patients being deemed to have "triple-negative" (TN) disease 1. Pathogenic mutations in JAK2, MPL, and CALR invariably lead to upregulation of JAK/signal transducer and activator of transcription (STAT) signaling and a heterogeneous clinical phenotype that often features dysfunctional hematopoiesis, constitutional symptoms, extramedullary hematopoiesis, and an increased propensity to develop acute myeloid leukemia (AML) 1.…”