expert roundtables

Complications in Sickle Cell Disease: Beyond the Most Common Offenders

by Stella T. Chou, MD; Michael Rutledge DeBaun, MD, MPH; and Julie Kanter, MD

Overview

Some of the complications of sickle cell disease (SCD) that may be more likely to go unrecognized or underdiagnosed include depression, post-transfusion alloimmunization, and silent infarcts with changes in cognitive function. Additionally, some patients may be reluctant to discuss other SCD-related complications, such as priapism or menstrual pain, unless asked directly.

Q:

Which complications of SCD require more attention, are more challenging to address, or might be at greater risk for being overlooked?

Julie Kanter, MD

Associate Professor, Division of Hematology and Oncology
Director, Adult Sickle Cell Program
Codirector, Lifespan Comprehensive Sickle Cell Center
University of Alabama at Birmingham
Birmingham, AL

“I would rank mental health and psychosocial issues highly among the conditions that may not receive as much attention as needed.”

Julie Kanter, MD

For me, I would rank mental health and psychosocial issues highly among the conditions that may not receive as much attention as needed, and this is especially true in young adults. We are not empowered as providers to do enough—that is, to really do the work that is needed to help affected individuals. I see that as a huge problem in our young adults. Even patients who have had the best treatment heretofore can encounter substantial challenges at this time having to do with their surroundings and their transition to adulthood. So, mental health, psychosocial support systems, and access to psychological care are areas that I think need more attention.

There are a variety of important complications of SCD that may be overlooked. Without creating a hierarchy, I would simply mention priapism because clinicians often forget to ask their patients about it, and it can be a significant detriment for those affected. Further, more research is needed on avascular necrosis in SCD, as it is one of the worst, most painful complications that causes severe chronic pain. And then, alloimmunization continues to be a major concern in this population. In my clinical practice, I see quite a few adult patients with antibodies following transfusion, and more needs to be done to identify this potential complication in those with SCD.

Stella T. Chou, MD

Associate Professor of Pediatrics
Chief, Division of Transfusion Medicine
Children’s Hospital of Philadelphia
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

“DHTR is a complication that is at risk for being missed, for a variety of reasons.”

Stella T. Chou, MD

Delayed hemolytic transfusion reaction (DHTR) is a complication that is at risk for being missed, for a variety of reasons. A patient might present with pain and fever, leading to hospital admission and treatment for pain, but it was not recognized that the patient was transfused in the 1 to 3 weeks prior to the current encounter. If the patient’s hemoglobin is low, that may lead to another transfusion. In a straightforward case, a new antibody may be detected in the pretransfusion antibody screen. However, the blood bank evaluation might not detect new antibodies, or perhaps the presence of antibodies is not evaluated as extensively as it could have been. In that scenario, the anemia may be due to hemolysis, and the patient with a DHTR may hemolyze the additional transfused red blood cells, which leads to a downward spiral.

Even at my institution, where I feel that the staff are generally well versed in the transfusion management of patients with SCD, DHTR is still an ongoing challenge. We performed a retrospective analysis of patients with new antibodies over a 14-year period and found that 30% of the patients with SCD and a new antibody had laboratory evidence of a DHTR, which was identified by the change in hemoglobin and hemoglobin S percentage at the time of new antibody detection. Of these, less than half of the cases were recognized by the patient or provider at the time of the event. Some DHTRs can be associated with mild symptoms, but if you were to transfuse those patients again, it could result in a more significant DHTR. I think that there are numerous transfusion-related issues that arise, and there is probably quite a bit more education and research that could be done in this area to help ensure that the risks related to DHTR are better recognized.

Michael Rutledge DeBaun, MD, MPH

Professor of Pediatrics and Medicine
Vice Chair for Clinical and Translational Research
J.C. Peterson Chair in Pediatrics
Director, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease
Vanderbilt University Medical Center
Nashville, TN

"Depression and cognitive impairment are both prevalent in children and adults with SCD, and they often go undiagnosed. Other common complications that may be devastating to individuals with SCD but are poorly studied include leg ulcers, priapism, and menstrual pain, owing to embarrassment or a reluctance to address these issues.”

Michael Rutledge DeBaun, MD, MPH

Depression and cognitive impairment are both prevalent in children and adults with SCD, and they often go undiagnosed. Other common complications that may be devastating to individuals with SCD but are poorly studied include leg ulcers, priapism, and menstrual pain, owing to embarrassment or a reluctance to talk about or address these issues. However, the most prominent challenge in the management of SCD is the absence of a primary care provider to facilitate the management of non-SCD complications. The vast majority of adults with SCD do not have primary care providers who work in partnership with hematologists to co-manage their care.

Silent stroke and cognitive impairment are fundamental concerns for parents of children with SCD, students with SCD, and adults with sickle cell anemia. We know that more than 30% and 50% of the children and adults with sickle cell anemia have silent cerebral infarcts, respectively, with an associated decrease in cognitive impairment. When this observation is combined with the fact that a disproportionate number of children with SCD in the United States are African Americans who attend underserved schools, these students are at a significant disadvantage. Students with silent cerebral infarcts lack overt manifestations of a focal neurological deficit. They are often not identified as having cognitive impairment; thus, they are not eligible for special services to augment educational attainment. As these patients get older, they are expected to be intellectually capable and financially independent, but their impaired cognitive skills may make this goal nearly impossible to attain.

The main challenge that clinicians and families face is the lack of SCD-based, evidence-based guidelines for depression, cognitive impairment, leg ulcers, priapism, or pain associated with menstruation.

References

Asare EV, Olayemi E, Boafor T, et al. Third trimester and early postpartum period of pregnancy have the greatest risk for ACS in women with SCD. Am J Hematol. 2019;94(12):E328-E331. doi:10.1002/ajh.25643

Brandow AM, DeBaun MR. Key components of pain management for children and adults with sickle cell disease. Hematol Oncol Clin North Am. 2018;32(3):535-550. doi:10.1016/j.hoc.2018.01.014

Chou ST, Alsawas M, Fasano RM, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327-355. doi:10.1182/bloodadvances.2019001143

Coleman S, Westhoff CM, Friedman DF, Chou ST. Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions. Transfusion. 2019;59(7):2282-2291. doi: 10.1111/trf.15328

DeBaun MR, Kirkham FJ. Central nervous system complications and management in sickle cell disease. Blood. 2016;127(7):829-838. doi:10.1182/blood-2015-09-618579

Onyeaka HK, Queeneth U, Rashid W, et al. Impact of depression in sickle cell disease hospitalization-related outcomes: an analysis of the national inpatient sample (NIS). Medicina (Kaunas). 2019;55(7):385. doi:10.3390/medicina55070385

Pecker LH, Darbari DS. Psychosocial and affective comorbidities in sickle cell disease. Neurosci Lett. 2019;705:1-6. doi: 10.1016/j.neulet.2019.04.011

Prussien KV, DeBaun MR, Yarboi J, et al. Cognitive function, coping, and depressive symptoms in children and adolescents with sickle cell disease. J Pediatr Psychol. 2018;43(5):543-551. doi:10.1093/jpepsy/jsx141

Sharma D, Day ME, Stimpson SJ, et al. Acute vaso-occlusive pain is temporally associated with the onset of menstruation in women with sickle cell disease. J Womens Health (Larchmt). 2019;28(2):162-169. doi:10.1089/jwh.2018.7147

Stimpson SJ, Rebele EC, DeBaun MR. Common gynecological challenges in adolescents with sickle cell disease. Expert Rev Hematol. 2016;9(2):187-96. doi:10.1586/17474086.2016.1126177

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