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Editorials
Underlying endothelial dysfunction and abnormal expres- sion of procoagulants such as tissue factor could also place SCD patients at a greater risk of thromboinflammation and thrombotic events if infected with SARS-CoV-2.14 Data from the US have shown higher rates of symptomatic infection requiring hospitalization and death in patients of African American and Hispanic ethnicity highlighting racial health disparities which impact the SCD community.15
Importantly, COVID-19 directed therapies such as anti- malarial agents (hydroxychloroquine or chloroquine) may confer additional risks and must be considered carefully given conflicting data regarding effectiveness.16,17 One well known adverse effect is methemoglobinemia, particularly in individuals with concomitant G6PD deficiency. Over a 4- week period in a single health system, eight COVID-19 patients who were treated with hydroxychloroquine devel- oped methemoglobinemia which was significant in three patients necessitating treatment with methylene blue.18 Of note, 1 of the 3 patients who developed acute hemolysis was found to have a new diagnosis of G6PD deficiency. In this respect, hydroxychloroquine treatment presents addi- tional risks in SCD patients in whom concomitant G6PD deficiency is not uncommon; in addition to other adverse cardiac effects including QT prolongation and ventricular arrythmias.
Strategies to optimize management of SCD patients during the COVID-19 pandemic
Hematologists caring for SCD patients have transitioned to telemedicine to reduce unnecessary exposure to SARS- CoV-2 in healthcare settings. Given asymptomatic trans- mission, healthcare providers should be vigilant in educa- ting patients regarding social isolation practices in their geo- graphic area, hand hygiene, and precautions when in public settings. Patients should be encouraged to be adherent to disease modifying therapies such as hydroxyurea to reduce the frequency of VOC episodes requiring medical attention. Laboratory monitoring for hydroxyurea and iron chelating drugs may need to be done less frequently, and when feasi- ble, medications should be mailed or delivered to the home. Routine visits to the clinic or hospital should be avoided unless phone triage indicates acute symptoms requiring medical evaluation. Some individuals may be able to man- age uncomplicated pain crises at home with optimization of oral opioid regimens and close supervision from health- care providers. Clinical teams should develop dedicated care pathways including phone screening to assess for COVID-19 symptoms prior to a scheduled visit, clinical screening before physical entrance including temperature measurement and symptom assessment, physical distanc- ing in waiting areas, as well as treatment in COVID-19 free clinical areas or isolation rooms. Cross-coverage of providers in the inpatient and outpatient setting should be limited and rotating clinical team schedules are encouraged to reduce the asymptomatic spread of SARS-CoV-2.
Strategies to decrease blood utilization in the setting of blood shortages
In the pandemic setting, there is a risk of severe blood shortages due not only to a decrease in donor participa- tion but a decrease in personnel to collect and process blood. Regular blood transfusion is standard therapy for
patients who have suffered an overt stroke as this offers the greatest protection from recurrence of further strokes; such patients should continue to receive transfusions in the presence of adequate blood supply. Patients with abnormal transcranial doppler (TCD) measurements may be eligible for transition to hydroxyurea therapy as per TWiTCH trial criteria for the prevention of a primary stroke.19,20 In order to preempt the possibility of blood supply interruption, it has been suggested that all children on blood transfusion therapy for primary and secondary stroke prevention should be started on low-dose hydro- xyurea (HU) therapy (fixed 10 mg/kg/day).21 Dose escala- tion of HU requires frequent laboratory monitoring of peripheral blood counts which may be undesirable in areas with high rates of community spread. DeBaun emphasizes that there can only be advantages in initiating low-dose HU therapy for patients on transfusion pro- grams for stroke prevention – low-dose HU has a mini- mal risk of myelosuppression, starting low-dose HU will decrease the lag time for clinical benefits if transfusions are suspended, and low-dose HU confers additional clini- cal benefits, such as reducing the frequency of VOC and ACS. Another approach to conserve blood during the COVID-19 pandemic is to dose-escalate hydroxyurea as this may reduce transfusion needs in SCD patients with a history of stroke.22 Outside stroke prevention, transfusion hemoglobin thresholds may be relaxed in patients with- out cardiopulmonary comorbidities in the absence of acute symptoms or organ dysfunction secondary to ane- mia. Simple blood transfusions may be substituted for exchange regimens and Hb S goals could also be relaxed (e.g., Hb S of 40% instead of 30%).20 Routine pre-transfu- sion laboratory work should be performed on the day of a scheduled transfusion to reduce unnecessary exposure to healthcare settings. Advanced planning for patients with extensive alloimmunization is necessary given that matched blood products may be difficult to source; trans- fusion of the least incompatible blood product with ritu- ximab prophylaxis may be considered in emergency situ- ations due to life-threatening anemia.23 A triage of manag- ing SCD patients in the COVID-19 pandemic setting is proposed in Figure 1.
Conclusions
Many unknown factors remain when considering the impact of COVID-19 in SCD patients. From published case reports, it is not clear if SCD increases the risk of SARS-CoV-2 infection. What is clear, is that fever is not always a feature, acute pain is a common presentation and COVID-19 can induce ACS but patients can recover fully with adequate supportive care. Importantly, lifesa- ving measures including mechanical ventilation should not be withheld from patients with SCD in the midst of this pandemic.
References
1. Fauci AS, Lane HC, Redfield RR. Covid-19 - Navigating the unchart- ed. N Engl J Med. 2020;382(13):1268-1269.
2. Organization WH. Coronavirus disease (COVID-19) situation sum- mary. 2020 [cited; Available from: https://www.who.int/emergen- cies/diseases/novel-coronavirus-2019/situation-reports].
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