Pregnancy outcomes in women with sickle cell disease in California.

Adverse pregnancy outcomes occur frequently in women with sickle cell disease (SCD) across the globe. In the United States, Black women experience disproportionately worse maternal health outcomes than all other racial groups. To better understand how social determinants of health impact SCD maternal morbidity, we used California's Department of Health Care Access and Information data (1991-2019) to estimate the cumulative incidence of pregnancy outcomes in Black women with and without SCD-adjusted for age, insurance status, and Distressed Community Index (DCI) scores. Black pregnant women with SCD were more likely to deliver at a younger age, use government insurance, and live in at-risk or distressed neighborhoods, compared to those without SCD. They also experienced higher stillbirths (26.8, 95% confidence interval [CI]: 17.5-36.1 vs. 12.4 [CI: 12.1-12.7], per 1000 births) and inpatient maternal mortality (344.5 [CI: 337.6-682.2] vs. 6.1 [CI: 2.3-8.4], per 100 000 live births). Multivariate logistic regression models showed Black pregnant women with SCD had significantly higher odds ratios (OR) for sepsis (OR 14.89, CI: 10.81, 20.52), venous thromboembolism (OR 13.60, CI: 9.16, 20.20), and postpartum hemorrhage (OR 2.25, CI 1.79-2.82), with peak onset in the second trimester, third trimester, and six weeks postpartum, respectively. Despite adjusting for sociodemographic factors, Black women with SCD still experienced significantly worse pregnancy outcomes than those without SCD. We need additional studies to determine if early introduction to reproductive health education, continuation of SCD-modifying therapies during pregnancy, and increasing access to multidisciplinary perinatal care can reduce morbidity in pregnant women with SCD.

Urinary cross-linked carboxyterminal telopeptide, a bone resorption marker, decreases after vaso-occlusive crises in adults with sickle cell disease.

People with sickle cell disease often report severe bone pain with repeated bouts of vaso-occlusive crises, but the extent of skeletal injury incurred during these painful episodes remain unclear. We sought to quantify bone degradation by comparing urinary concentrations of carboxyterminal cross-linked telopeptide of type I collagen (CTX-1), a well-described marker of bone resorption, in a prospective cohort of 52 adults with sickle cell disease enrolled in the Sickle Cell Pain Markers Study. We also questioned if changes in urinary CTX-1 concentrations correlated with changes in hemolysis and inflammatory markers measured both during and after resolution of a painful vaso-occlusive episode. Thirty-one of the 52 adults enrolled in the study had paired urine samples for CTX-1 analysis. Urinary CTX-1, corrected for urine creatinine, significantly decreased from a mean of 3.45 µg/mmol during vaso-occlusive crises to 2.62 µg/mmol at recovery (p = 0.01). Thus, increased bone loss appears to correlate with acute vaso-occlusive crises in sickle cell disease. Our finding that urinary CTX-1 can be used to probe bone degradation in sickle cell disease provides an important new tool for diagnosing and monitoring response to therapy for people with sickle cell-related bone loss.

Clinical Vignettes, Part II: Eyes, Teeth, and Bone.

Microvascular occlusions caused by sickle cell disease (SCD) can affect all ocular and orbital structures. Sickle cell retinopathy (SCR) is the most common ophthalmic manifestation of SCD. Fortunately, most individuals with SCR are visually asymptomatic. Vision loss in SCD most commonly occurs as a consequence of proliferative sickle cell retinopathy (PSR), in which pathologic retinal neovascularization occurs. To prevent significant vision loss and blindness, which can occur from complications of PSR, regular retinopathy surveillance screening examinations and consistent follow-up with a retina specialist are recommended. Scatter laser photocoagulation is the current gold-standard treatment to prevent vision threatening progression of PSR. Patients with sickle cell disease should have regular checkups with their dental care provider. Patients should be educated on the importance of proper dental care, a healthy diet, and the need for early intervention if they suspect any dental problems or are having dental pain. If any dental procedures that involve surgery or sedation are planned, it is critical to consult with the hematologist before the procedure is started. Prophylactic antibiotics may have to be prescribed before invasive dental procedures, such as extractions or periodontal surgery but is best determined by discussions between the dental care provider and the hematologist. Osteonecrosis is a highly prevalent skeletal complication of sickle cell disease that affects all genotypes. Risk factors for osteonecrosis include older age, HbSS genotype with concomitant alpha-thalassemia trait, frequent vaso-occlusive episodes, history of acute chest syndrome, elevated body mass index, and low white blood cell counts. Osteonecrosis causes progressive joint damage and associates with chronic pain, frequent acute care visits, and overall poor health-related quality of life. Current consensus guidelines recommend analgesics, physical therapy, and early consideration of joint arthroplasty in sickle cell-related osteonecrosis, although surgery may be deferred until late adolescence after growth plates have fused.

Acute Care Utilization at End of Life in Sickle Cell Disease: Highlighting the Need for a Palliative Approach.

Background: People with sickle cell disease (SCD) have a life expectancy of <50 years, so understanding their end-of-life care is critical. Objective: We aimed to determine where individuals with SCD were dying and their patterns of care in the year preceding death to highlight end-of-life research priorities and possible opportunities for intervention. Design: Using the California SCD Data Collection Program database (containing administrative data, vital records, and Medicaid claims), we examined people with SCD who died between 2006 and 2015 (cases) at age <80 years and examined their hospital and emergency department (ED) utilization in their last year of life. Comparators included living controls with SCD matched 1:1 based on age, analysis year, insurance, and income. Results: We identified 486 people with SCD (cases) who died at a median age of 45 years (SD: 16 years). Most died in the hospital (63%) and ED (15%). In their last year of life, people with SCD were hospitalized for an average of 42 days (SD: 49 days) over five admissions. Inpatient admissions and ED visits were stable throughout the year until the month before death when acute care utilization sharply increased. In their last year of life, cases had more hospitalizations than controls, but similar ED utilization. Conclusions: People with SCD are dying acutely at a young age and most die in the hospital and the ED. Since clinicians caring for people with SCD currently cannot predict which acute events may be life-threatening, a comprehensive palliative approach to people with SCD must extend beyond chronic pain management and psychosocial support to include advance care planning.

Osteonecrosis in sickle cell disease: an update on risk factors, diagnosis, and management.

Osteonecrosis, a form of ischemic bone injury that leads to degenerative joint disease, affects ∼30% of people with sickle cell disease. Although osteonecrosis most commonly affects the femoral head (often bilaterally, with asymmetric clinical and radiographic progression), many people with sickle cell disease also present with multifocal joint involvement. We present the case of a young woman with bilateral osteonecrosis of the femoral head at varying stages of progression; we also highlight other important comorbid complications (eg, chronic pain requiring long-term opioids, debility, and social isolation) and postoperative outcomes. In this review, partly based on recommendations on osteonecrosis management from the 2014 evidence-based report on sickle cell disease from the National Heart, Lung and Blood Institutes, we also discuss early signs or symptoms of osteonecrosis of the femoral head, radiographic diagnosis and staging criteria, hydroxyurea effect on progression to femoral head collapse, and surgical outcomes of total hip arthroplasty in the modern era. In summary, we failed to find an association between hydroxyurea use and femoral head osteonecrosis; we also showed that evidence-based perioperative sickle cell disease management resulted in superior postoperative outcomes after cementless total hip arthroplasty in sickle cell-related osteonecrosis of the femoral head.

Height-corrected low bone density associates with severe outcomes in sickle cell disease: SCCRIP cohort study results.

Low bone mineral density (BMD) disproportionately affects people with sickle cell disease (SCD). Growth faltering is common in SCD, but most BMD studies in pediatric SCD cohorts fail to adjust for short stature. We examined low BMD prevalence in 6- to 18-year-olds enrolled in the Sickle Cell Clinical Research and Intervention Program (SCCRIP), an ongoing multicenter life span SCD cohort study initiated in 2014. We calculated areal BMD for chronological age and height-adjusted areal BMD (Ht-aBMD) z scores for the SCCRIP cohort, using reference data from healthy African American children and adolescents enrolled in the Bone Mineral Density in Childhood Study. We defined low BMD as Ht-aBMD z scores less than or equal to -2 and evaluated its associations with demographic and clinical characteristics by using logistic regression analyses. Of the 306 children and adolescents in our study cohort (mean age, 12.5 years; 50% female; 64% HbSS/Sß0-thalassemia genotype; 99% African American), 31% had low areal BMD for chronological age z scores and 18% had low Ht-aBMD z scores. In multivariate analyses, low Ht-aBMD z scores associated with adolescence (odds ratio [OR], 7.7; 95% confidence interval [CI], 1.94-30.20), hip osteonecrosis (OR, 4.0; 95% CI, 1.02-15.63), chronic pain (OR, 10.4; 95% CI, 1.51-71.24), and hemoglobin (OR, 0.74; 95% CI, 0.57-0.96). Despite adjusting for height, nearly 20% of this pediatric SCD cohort still had very low BMD. As the SCCRIP cohort matures, we plan to prospectively evaluate the longitudinal relationship between Ht-aBMD z scores and markers of SCD severity and morbidity.