Severe delayed hemolytic transfusion reaction due to anti-Fy3 in a patient with sickle cell disease undergoing red cell exchange prior to hematopoietic progenitor cell collection for gene therapy

Stone, Elizabeth F.; Avecilla, Scott T.; Wuest, David; Lomas‐Francis, Christine; Westhoff, Connie M.; Diuguid, David L.; Sadelain, Michel; Boulad, Farid; Shi, Patricia A.

doi:10.3324/haematol.2020.253229

Cited by 9 publications

(8 citation statements)

References 13 publications

(7 reference statements)

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“…It should be noted that patients of African ancestry with the canonical FY GATA mutation can still make alloanti‐Fy3/Fy5 if exposed to Fy b antigen‐positive RBC, as with our patient. 30 , 31 This complex auto‐ and alloimmunization event necessitated multiple work‐ups and send‐out to two different immunohematology reference labs, including our blood supplier's national reference lab.…”

Section: Discussionmentioning

confidence: 99%

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

et al. 2022

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Background: Hyperhemolysis syndrome (HHS) is a severe delayed hemolytic transfusion reaction seen in sickle cell disease (SCD) patients, characterized by destruction of donor and recipient RBCs. It results in a drop in hemoglobin to below pretransfusion levels and frequently reticulocytopenia. Case Report: We report a case of a man in his thirties with SCD with a recent hospitalization 2 weeks prior for COVID-19. His red cell antibody history included anti-Fy(a) and warm autoantibody. At that time, he was given 2 units of RBC and discharged with a hemoglobin of 10.2 g/dl.He returned to the hospital approximately 1.5 weeks later with hemoglobin 6.0 g/dl and symptoms concerning for acute chest syndrome. Pretransfusion testing now showed 4+ pan-agglutinin in both gel-based and tube-based testing. Alloadsorption identified an anti-N and a strong cold agglutinin. Three least incompatible units were transfused to this patient over several days, with evidence of hemolysis. Further reference lab work revealed anti-Fy a , anti-Fy b , anti-Le a , anti-Le b , and an anti-KN system antibody. The patient's hemoglobin nadired at 4.4 g/dl. The patient was treated with a single dose of tocilizumab, his hemoglobin stabilized, and he was discharged. Discussion: We present a case of HHS proximate to recent SARS-CoV-2 infection with multiple allo and autoantibodies identified. Information on the relationship between SARS-CoV-2 infection and HHS is limited; however, it is possible that inflammation related to COVID-19 could predispose to HHS.Tocilizumab is an approved treatment for COVID-19. Additionally, tocilizumab appears to be a promising treatment option for patients with HHS.

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Section: Discussionmentioning

confidence: 99%

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

et al. 2022

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“…It is well documented that transfusional iron overload is a major cause of toxicity in patients with b-thalassemia, but for reasons that remain incompletely understood, patients with SCD are at relatively lower risk of such iron-related complications. [52][53][54] Nevertheless, transfusions do carry risks, including hemolytic transfusion reactions in SCD, 55,56 underscoring the need for developing optimal transfusion management strategies such as establishment of guidelines for prophylactic matching as well as the number and frequency of units necessary for transfusion for improving the bone marrow niche.…”

Section: Discussionmentioning

confidence: 99%

Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease

Tang¹,

Strat²,

Rahman³

et al. 2021

Blood

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Sickle Cell Disease (SCD) is characterized by hemolytic anemia, which can trigger oxidative stress, inflammation, and tissue injury that contributes to disease complications. Bone marrow mesenchymal stromal cells (MSCs) tightly regulate hematopoietic stem cell (HSC) homeostasis in health and disease but their functionality in SCD remains unclear. We identified for the first time murine SCD MSCs to have altered gene signatures, reduced stem cell properties, and increased oxidative stress, due in part to hemolysis. Murine SCD MSCs had lower HSC maintenance ability in vitro and in vivo as manifested by increased HSC mobilization and decreased HSC engraftment following transplant. Activation of TLR4 through p65 in MSCs further contributed to MSC dysfunction. Transfusions led to improved MSC and HSC oxidative state in SCD mice. Improving the regulation between MSCs and HSCs has vital implications for enhancing clinical HSC transplantation and gene therapy outcomes and for identification of new molecular targets for alleviating SCD complications.

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“…6 It is impor tant for phy si cians car ing for patients with SCD, includ ing those in emer gency depart ments, to be aware that the symp toms of a DHTR may resem ble a vaso occlu sive cri sis. 7 A high degree of sus pi cion for DHTR should be maintained in any patient trans fused in the past month who has symp toms includ ing pain. A com plete blood count (CBC), retic u lo cyte count, chem is tries, LDH, uri nal y sis, Hgb A and S quan ti fi ca tion, type and screen (to eval u ate for any new antibodies in the patient's serum), and direct anti glob u lin test (DAT; to eval u ate antibodies coat ing either the patient's own RBCs or past trans fused RBCs) should be drawn.…”

Section: Pathophysiology Of Delayed Hemo Lytic Trans Fu Sion Reac Tionsmentioning

confidence: 99%

“…There is no "right" answer to the risk/ben e fit ques tion, but this sce nario increas ingly pres ents itself as the num ber of poten tially cura tive ther a pies for SCD rises in num ber. The neces sity of low er ing the Hgb S prior to stem cell trans plan ta tion or periph eral blood stem cell col lec tion (for gene ther apy or for other indi ca tions) is not clear, 7,38 although most pro to cols rec om mend low er ing the Hgb S to decrease trans plantrelated com pli ca tions, to decrease mobi li za tioninduced vasoocclu sion, and/or to improve stem cell mobi li za tion from the mar row. However, patients who have pre vi ously had DHTRs are at increased risk of hav ing future (poten tially lifethreat en ing) DHTRs with RBC expo sure even years later and even when exten sively phe no typ i cally matched RBCs are selected for trans fu sion.…”

Section: Future Trans Fu Sion Con Sid Er Ationsmentioning

confidence: 99%

“…As such, edu cat ing the fam ily and the involved care teams on the poten tial risks is impor tant; case reports describe cura tive ther a pies being can celled or delayed as a result of DHTRs fol low ing pretrans plant trans fu sions. 7,39 Furthermore, the opti mal stem cell donor would lack the cog nate RBC anti gens against which the patient is alloimmunized, but HLA matching takes pri or ity, and in some instances, RBC anti gen avoid ance is not pos si ble.…”

Section: Future Trans Fu Sion Con Sid Er Ationsmentioning

confidence: 99%

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Management of hemolytic transfusion reactions

Hendrickson

Fasano

2021

Hematology

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Delayed hemolytic transfusion reactions (DHTRs) in patients with sickle cell disease are underappreciated and potentially fatal. Patients with DHTRs typically have symptoms of pain or dark urine days to weeks following a red blood cell (RBC) transfusion. In instances of DHTRs with hyperhemolysis, the patient's hemoglobin (Hgb) may be significantly lower than it was pretransfusion, and the Hgb A may drop by more than 50%. In most cases, at least 1 RBC alloantibody and sometimes multiple RBC alloantibodies can be identified during the DHTR, with those antibodies presumably having fallen below the level of detection at the time of the implicated transfusion. However, in up to one-third of cases, no new RBC alloantibodies can be identified posttransfusion. Complement is increasingly being appreciated to play a role in DHTRs and hyperhemolysis, not only due to classic pathway activation (with complement fixed antibody bound to RBCs) but also due to alternative pathway activation (resulting in part from plasma free heme). As such, anti-C5 inhibition has recently been reported to be effective at mitigating hemolysis in the setting of some severe DHTRs. Transfusion avoidance during DHTRs is recommended if possible, with long-term transfusion support advice being less clear; for example, a history of a severe DHTR may lead to questions regarding the safety of transfusions prior to curative therapies such as stem cell transplantation or gene therapy. A better understanding of antibody-positive and antibody-negative DHTRs, including patient- or disease-specific risk factors, is necessary to improve transfusion safety.

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Severe delayed hemolytic transfusion reaction due to anti-Fy3 in a patient with sickle cell disease undergoing red cell exchange prior to hematopoietic progenitor cell collection for gene therapy

Abstract: Severe delayed hemolytic transfusion reaction due to anti-Fy3 in a patient with sickle cell disease undergoing red cell exchange prior to hematopoietic progenitor cell collection for gene therapy.

Cited by 9 publications

References 13 publications

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

Hyperhemolysis in a patient with sickle cell disease and recent SARS‐CoV‐2 infection, with complex auto‐ and alloantibody work‐up, successfully treated with tocilizumab

Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease

Management of hemolytic transfusion reactions

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