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This is a post-peer-review, pre-copyedited version of an article published in Annals of Hematology.

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According to the Center of Disease Control and Prevention (CDC) database, the total number of deaths due to opioid overdose from 1999 through 2018 was 840,629. Given the alarming nature of these statistics, patients who requested prescription for opioids became targets of suspicion and possible accusation of maladaptive behavior. Patients with sickle cell disease (SCD) were often not exempt from such accusations and became guilty by association. In order to clarify the effect of opioids on the mortality of patients with SCD, the mortality rates for children and adults with SCD were investigated using the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death database which is based on all the death certificates issued in the USA from 1999 to 2018. The data showed that 15,765 patients with SCD died from 1999 to 2018. Only 348 patients with SCD died due to opioids. The CDC database contains 27 categories of death based on ICD-10 codes in patients with SCD, and opioids were the 19th ranking cause of death. Surprisingly the most common causes of death of patients with SCD included circulatory, infection, respiratory, genitourinary, and vaso-occlusive crises/acute chest syndrome disorders in decreasing frequency. The mean age of death of females was 41.9 years and of males 39.3 years (p < 0.0001). Death due to SCD and death due to SCD and opioids were highest in the Southern Region of the USA.



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