Diagnosis of Bone Marrow Necrosis following Severe Vaso-Occlusive Crisis in Patient with Compound Heterozygous Sickle Cell Disease

Introduction: Bone marrow necrosis is a rare entity that can develop in context of a sickle cell disease vaso-occlusive crisis. Its physiopathology is related to an endothelial dysfunction taking place in bone marrow microvasculature. Case Presentation: A 30-year-old patient with history of compound heterozygous sickle cell disease was admitted following SARS-CoV-2 infection with fever and diarrhea. After initial favorable evolution, he developed a severe vaso-occlusive crisis with intense hemolysis and multi-organ ischemic complications. Patient then developed high fever and hypoxemia. With the suspicion of acute thoracic syndrome, a red blood cell exchange was performed. Respiratory symptoms ceased but patient persisted febrile with very high levels of acute phase reactants, persistent pancytopenia, and leucoerythroblastic reaction. An infectious cause was ruled out. Afterward, bone marrow aspiration and bone marrow biopsy showed a picture of bone marrow necrosis, which is an extremely rare complication of vaso-occlusive crisis but, paradoxically, more frequent in milder heterozygote cases of sickle cell disease. Ultimately, large deposits of complement membrane attack complex (particles C5b-9) were demonstrated after incubation of laboratory endothelial cells with activated plasma from the patient. Discussion: The clinical presentation and findings are consistent with a case of bone marrow necrosis. In this setting, the demonstration of complement as a potential cause of the endothelial dysfunction mimics the pattern of atypical hemolytic uremic syndrome and other microangiopathic anemias. This dysregulation may be a potential therapeutic target for new complement activation blockers. [ FROM AUTHOR] Copyright of Transfusion Medicine & Hemotherapy is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Patient perception of voxelotor treatment benefit in sickle cell disease.

Patients with sickle cell disease (SCD) experience a range of clinical symptoms, including acute and chronic pain, fatigue, and respiratory problems, as well as chronic organ complications that can lead to disability and accelerated mortality. Voxelotor is a first-in-class therapy that targets sickle hemoglobin polymerization, the root cause of SCD. It is approved by the US Food and Drug Administration for treatment of SCD in patients aged 4 years and older and in the European Union and United Arab Emirates for the treatment of SCD in patients aged 12 years and older. Here, we report the single-center experience of both clinician-determined and patient-reported benefits of voxelotor in 27 consecutive patients treated for at least 8 weeks. Clinical Global Impression of Change and Patient Global Impression of Change rating scales were used to capture clinicians' and patients' perceptions of change in overall patient health-related quality-of-life with voxelotor treatment. Laboratory data were also collected to assess clinical response to treatment. As observed in previous clinical studies, hemoglobin concentrations and markers of hemolysis were improved in patients treated with voxelotor. Most patients reported marked improvement in disease symptoms, which correlated well with the clinicians' assessments. Although limited by the retrospective open-label study design, these findings suggest that voxelotor use has a positive impact on outcomes in patients with SCD.

Risk and protective factors for severe COVID-19 infection in a cohort of patients with sickle cell disease.

Continued investigation of comorbid conditions that increase the mortality rate of COVID-19 is necessary to provide the best care for those affected. This continued push to find answers is even more important for populations with COVID-19 comorbidities that are historically under-researched. We performed a retrospective analysis of 30 patients with sickle cell disease (SCD) who tested positive for the COVID-19 virus. An analysis of each patient's history of SCD complications, hydroxyurea usage, comorbidities, and several other factors was performed to identify the trends that will allow the practitioners to better predict the outcomes of patients with SCD before and during hospitalization for COVID-19. Through these analyses, we found that patients receiving hydroxyurea before COVID-19 infection and patients with SCD-type HbSC had significantly milder COVID-19 disease courses than those not receiving hydroxyurea or with SCD-type HbSS. A history of acute chest syndrome (ACS), a complication seen in patients with SCD, appeared to be associated with a more severe COVID-19 disease course. By creating systems to better interpret what makes a patient with SCD at high risk for a poor prognosis, practitioners are better equipped to make data-supported recommendations for prevention, risk, and treatment. These recommendations should include beginning or maintaining hydroxyurea usage in all qualifying patients with SCD, advising patients with a history of ACS to take extra precautions to prevent initial COVID-19 infection, and initiating close monitoring in the hospital for patients with HbSS and a history of ACS.