Asian Journal of Transfusion Science
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CASE REPORT  
Ahead of print publication
Anti-human leukocyte antigen-DPB1 antibody-associated transfusion-related acute lung injury after hematopoietic stem cell infusion


1 Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey
2 Department of Pediatric Hematology, Hematopoietic Stem Cell Transplantation Unit, Hacettepe University Medical Faculty, Ankara, Turkey
3 Department of Pediatric Hematology, Hematopoietic Stem Cell Transplantation Unit, Hacettepe University Medical Faculty; Department of Pediatric Hematology and Oncology, Baskent University Medical Faculty, Ankara, Turkey

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Date of Submission20-Dec-2021
Date of Decision31-Jan-2022
Date of Acceptance06-Feb-2022
Date of Web Publication26-Sep-2022
 

   Abstract 

Although relatively rare among transfusion reactions, transfusion-related acute lung injury (TRALI) is a life-threatening condition, making its prevention, recognition, and early intervention extremely important. Although many etiological factors have been identified, the most common reasons are anti-human leukocyte antigen (anti-HLA) and anti-human neutrophil antigen antibodies that pass from the donor to the recipient during transfusion. TRALI was shown with transfusion of all kinds of blood products, however, it is rarely seen after stem cell infusion. Despite an adult case who developed TRALI after stem cell infusion, there is no pediatric case of TRALI associated with hematopoietic stem cell infusion in the previous literature. Here, we report a pediatric case with TRALI after infusion of the hematopoietic stem cell product from his female donor who has recently given birth 6 months ago. A 9-year-old patient with acquired aplastic anemia was admitted for hematopoietic stem cell transplantation (HSCT) from an ABO and 10/10 HLA compatible 21-year-old sister donor the unmanipulated stem cell product was planned to be infused in 4 h. At the last hour of infusion, the patient had acute hypoxemia, tachycardia, and bilateral pulmonary edema. He was diagnosed with TRALI and completely recovered with supportive therapy in 48 h. The anti-HLA antibody analysis of the donor showed positivity of anti-HLA-DPB1 antibodies. We wanted to emphasize the need for examination of anti-HLA antibodies of the donor and plasma depletion of the product to avoid TRALI in HSCTs from multiparous female donors.

Keywords: Hematopoietic stem cell transplantation, transfusion-related acute lung injury, transfusion-related acute lung injury


How to cite this URL:
Balkan MC, Okur FV, Apak FB, Babayeva S, Ekici NF, Kuskonmaz B, Cetinkaya DU. Anti-human leukocyte antigen-DPB1 antibody-associated transfusion-related acute lung injury after hematopoietic stem cell infusion. Asian J Transfus Sci [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajts.org/preprintarticle.asp?id=356877



   Introduction Top


TRALI (Transfusion-related acute lung injury) is a life-threatening transfusion reaction and , its prevention, recognition, and early intervention is extremely important. The most common etiologic factors are anti-HLA (anti-Human Leucocyte Antigen) and anti-HNA (anti-Human Neutrophil Antigen) antibodies that pass from the donor to the recipient during transfusion. TRALI was shown with transfusion of all kinds of blood products, however, it is rarely seen after stem cell infusion. Here we report a pediatric case with TRALI after infusion of the hematopoietic stem cell product from his female donor who has recently given birth 6 months ago.


   Case Report Top


Transfusion-related acute lung injury (TRALI) is defined by the presence of acute-onset hypoxemia during or within the first 6 h of transfusion, findings consistent with bilateral pulmonary edema on radiological imaging, and the absence of the left atrial hypertension. Diagnosis is made clinically.[1] The majority of TRALI cases are caused by anti-human leukocyte antigen (anti-HLA) and anti-human neutrophil antigen (anti-HNA) antibodies. The frequency of TRALI has been estimated to be 0.08%–15.1% per patient and 0.01%–1.12% per product.[2] As a general framework of pathophysiology, the two-hit hypothesis was hypothesized for TRALI. The first hit occurs with the underlying comorbid condition that results in the activation of neutrophils from shock, sepsis, surgery, smoking, infection, mechanical ventilation, and positive fluid balance.[3],[4] After priming of neutrophils with inflammation, the second hit occurs due to transfusion itself. It is conveyed by anti-HLA and anti-HNA antibodies in the blood product in 80% of the cases. There is a single-reported case including an adult hematopoietic stem cell transplantation (HSCT) patient who had experienced TRALI during stem cell infusion.[5] Here, we report a pediatric case with TRALI after transfusion of the hematopoietic stem cell product from his female donor who has recently given birth to her first child.

A 9-year-old patient with acquired aplastic anemia was admitted for allogeneic HSCT from his 21-year-old sister, who was 10/10 compatible in terms of HLA-A, B, C, DRB1, and DQB1 in the HLA analysis. HLA-DPB1 was not analyzed. The patient had >20 erythrocyte and platelet transfusions during the pretransplant period without any transfusion reactions. The patient had invasive aspergillosis that required antifungal treatment for more than 2 months. Despite the HSCT was made from a full-matched donor, because of the history of transfusion and the risk of alloimmunization, anti-thymocyte globulin (ATG) were added to the conditioning regimen. The patient received the nonmyeloablative conditioning regimen of 200 mg/kg cyclophosphamide (-6 to-3) and 30 mg/kg ATG (-4 to-1) and graft versus host disease prophylaxis with methotrexate and cyclosporine. On the morning of day 0, he had neutropenic fever with 38.7°C and broad-spectrum antibiotics were initiated. Premedication with 1 mg/kg methylprednisolone, 1 mg/kg pheniramine, and 10 mg/kg paracetamol was given 30 min before infusion. 750 cc of bone marrow harvest stem cell product (nucleated cell: 3,8 × 108/kg, CD34: 6,5 × 106/kg, mononuclear cell: 0,98 × 108/kg, unmanipulated) was scheduled to be infused in 4 h. In the last hour of the infusion, the patient experienced headache, hypotension, tachycardia, tachypnea, and hypoxemia with SpO2 <90% at room air with body temperature: 37.7°C, heart rate: 158/min, respiratory rate: 50/min, and blood pressure: 90/50 mmHg. Bilateral rales were present at the examination. The laboratory findings were as; hemoglobin: 87 g/L, Htc: 24.2%, white blood cell count: 100 × 109/L, absolute neutrophil count: 0 × 109/L, platelets: 28 × 109/L, unremarkable biochemistry, C-reactive protein: 10.9 mg/dl, prothrombin time (international normalized ratio):1.19 (0.8–1.2) s, activated partial thromboplastin time: 29.2 s (22.5–32), fibrinogen: 401 g/L, D-dimer: 2.30 mg/L (0–0.55), and moderate hypoxemia at blood gases. The chest X-ray revealed bilateral diffuse infiltrates suggesting pulmonary edema and echocardiography was normal [Figure 1]. However, brain natriuretic protein (BNP) and troponin-I levels were increased as a sign of cardiac strain. Because of increased BNP, transfusion-related circulatory overload was also considered, however, his intravenous fluid intake and output was balanced with diuretic treatment and there was no improvement of respiratory effort of the patient. Mask oxygen therapy (4 L/min), furosemide, dopamine, inhaler salbutamol, adrenalin, and enalapril were initiated and the rest of the infusion was completed. Despite normal fluid balance, SpO2 decreased to 86% 2 h after the end of the infusion, and noninvasive mechanical ventilation was initiated. After 48 h, the ventilatory support was stopped and the pulmonary findings were completely resolved. After the TRALI diagnosis, anti-HLA antibody screening was performed from the pre-HSCT serum sample of the donor, and anti-DBP1 × 18 antibody was found to be positive. The antibody-antigen mismatch was observed with DPB1 antigen analysis performed on the pre-HSCT DNA sample of the recipient and the anti-DPB1 × 18 antibodies were thought to be causative.
Figure 1: The chest X-rays of the patient before and after transfusion-related acute lung injury reaction. (a) The chest X-ray day before stem cell infusion. (b) The chest X-ray at transfusion-related acute lung injury diagnosis

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   Discussion Top


An adult case of TRALI that occurred during stem cell infusion has been described in the literature.[5] This patient who had undergone HSCT from an ABO matched and HLA-1-mismatched donor had suffered from chronic parvovirus infection. The authors concluded that there was an unidentified antibody in the patient's serum before the infusion of marrow cells probably due to parvovirus infection and the neutrophils and plasma of the graft and preformed antibodies at the recipient may have caused the reaction. This showed that in practice, TRALI can occurs with multiple mechanisms and can be seen in neutropenic patients as in our case. We had to infuse the 750 cc (25 cc/kg) bone marrow stem cell harvest to reach the targeted CD34 cell count in the graft, and the avoid circulatory overload we had almost finished the infusion at the time the patient was detoriated. Despite increased BNP may show that circulatory overload may have contributed to the clinical picture, we think that the diagnosis is much more like TRALI, as the patient did not show clinical progress with diuretics leading to normal fluid balance.

At our TRALI etiologic work-up, the pretransplant donor plasma revealed anti-DPB1 antibody positivity. A mismatch at the HLA-DPB* allele was also shown between the donor and the recipient at the pretransplant DNA samples. The antibody types mainly associate with TRALI are HLA-A2, -DR4, and DR52, however, DPB1 is also reported.[6]

At the formation of TRALI, the previous activation of the immune system and sustained inflammation of the patient also contributes to the pathogenesis. Although neutrophil sequestration plays an important role in the pathogenesis, it has been shown recently that high titers of HLA Class II antibodies can also cause TRALI by the activation of NADPH oxidase in the pulmonary endothelium.[7] In our patient, we think that the ongoing subtle inflammation which is exacerbated by anti-HLA DPB1 antibody-dependent endothelial activation may have caused the reaction. The incidence of anti-HLA and anti-HNA antibodies is much higher in plasma-rich blood products donated by multiparous women. TRALI has been decreased after the deferral policy of multiparous female donors, particularly from plasma-rich blood product donations or screening for anti-HLA and anti-HNA antibodies at female donors.[8],[9] However, it is not always feasible to exclude multiparous stem cell donors from the donation. In our case, only the older sister of the recipient was found compatible as a donor. We think that routine screening for anti-HLA and anti-HNA antibodies from female donors before HSCT, closer monitoring in terms of TRALI risk in the presence of antibodies, and routine plasma reduction in stem cell products obtained from female donors would be practical approaches.

Informed consent

Informed consent was obtained from the caregiver of the patient for publication of his clinical data.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, et al. Transfusion-related acute lung injury: Definition and review. Crit Care Med 2005;33:721-6.  Back to cited text no. 1
    
2.
Sapiano MR, Savinkina AA, Ellingson KD, Haass KA, Baker ML, Henry RA, et al. Supplemental findings from the National Blood Collection and Utilization Surveys, 2013 and 2015. Transfusion 2017;57 Suppl 2:1599-624.  Back to cited text no. 2
    
3.
Toy P, Gajic O, Bacchetti P, Looney MR, Gropper MA, Hubmayr R, et al. Transfusion-related acute lung injury: İncidence and risk factors. Blood 2012;119:1757-67.  Back to cited text no. 3
    
4.
Peters AL, van Hezel ME, Juffermans NP, Vlaar AP. Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside. Blood Rev 2015;29:51-61.  Back to cited text no. 4
    
5.
Urahama N, Tanosaki R, Masahiro K, Iijima K, Chizuka A, Kim SW, et al. TRALI after the infusion of marrow cells in a patient with acute lymphoblastic leukemia. Transfusion 2003;43:1553-7.  Back to cited text no. 5
    
6.
Odent-Malaure H, Quainon F, Ruyer-Dumontier P, Ducroz S, Verdier P, Voitellier E, et al. Transfusion Related Acute Lung İnjury (TRALI) caused by red blood cell transfusion involving residual plasma anti-HLA antibodies: A report on two cases and general considerations. Clin Dev Immunol 2005;12:243-8.  Back to cited text no. 6
    
7.
Kopko PM, Popovsky MA, MacKenzie MR, Paglieroni TG, Muto KN, Holland PV. HLA class II antibodies in transfusion-related acute lung injury. Transfusion 2001;41:1244-8.  Back to cited text no. 7
    
8.
Eder AF, Herron RM Jr., Strupp A, Dy B, White J, Notari EP, et al. (2010), Effective reduction of transfusion-related acute lung injury risk with male-predominant plasma strategy in the American Red Cross (2006-2008). Transfusion 2010;50:1732-42.  Back to cited text no. 8
    
9.
Müller MC, van Stein D, Binnekade JM, van Rhenen DJ, Vlaar AP. Low-risk transfusion-related acute lung injury donor strategies and the impact on the onset of transfusion-related acute lung injury: A meta-analysis. Transfusion 2015;55:164-75.  Back to cited text no. 9
    

Top
Correspondence Address:
Fatma Burcu Belen Apak,
Department of Pediatric Hematology and Oncology, Baskent University Medical Faculty, Sehit Temel Kuguluoglu Street No: 24, Bahcelievler, Ankara 06490
Turkey
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.ajts_187_21



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2006 - Asian Journal of Transfusion Science | Published by Wolters Kluwer - Medknow
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