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\begin{document}

\title{Transfusion-related acute lung injury (TRALI) caused due to the
antibodies HLA-DRB1* 07:01 and HLA-DQB1*02:02: a case report}



\author[1]{Menggentuya Huang}%
\author[1]{Xingtong Wang}%
\author[1]{Li Wang}%
\author[1]{Guanyi Chen}%
\affil[1]{Fourth Medical Center of PLA General Hospital}%


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  \date{May 25, 2024}


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Transfusion-related acute lung injury (TRALI) caused due to the
antibodies HLA-DRB1* 07:01 and HLA-DQB1*02:02: a case report

\textbf{Key Clinical Message}

Transfusion-related acute lung injury (TRALI) is characterized by
non-cardiogenic pulmonary oedema and acute hypoxemia. TRALI attributed
to HLA-II antibodies is infrequently reported in China.

\textbf{Keywords:} Transfusion-related acute lung injury; HLA class II
antibodies; pulmonary edema; blood transfusion

\textbf{Introduction}

The Food and Drug Administration (FDA) reports that transfusion-related
acute lung injury (TRALI) is the main reason behind morbidity and
mortality associated with transfusion.\textsuperscript{1} This condition
is characterized by the sudden appearance of non-cardiogenic pulmonary
edema and hypoxemia within six hours of blood transfusion. According to
data from the International Haemovigilance (HV) Network, the morbidity
rate of TRALI is 0.0494 per 100,000 parts of blood transfused.
Additionally, the mortality rate of TRALI among the general patient
population is approximately 10-15\%, reaching nearly 40\% in critically
ill patients.\textsuperscript{2,3} In Chinese populations, the morbidity
and mortality rate of TRALI remains unclear due to insufficient disease
awareness, incomplete reporting systems, and HV data. We attempt to
raise awareness among clinicians by reviewing a patient who developed
TRALI after receiving frozen plasma controlled by HLA-II antibodies. The
successful treatment of this patient indicates the necessity of accurate
management in TRALI cases.

\textbf{Case report with results}

Our hospital admitted a 52-year-old male patient suffering over a month
from head and neck skin ulceration and purulent secretions. The
temperature of his body was 36.8\selectlanguage{ngerman}°C, with a pulse rate of 67 beats/min, a
pressure level of 120/76 mmHg in the blood, and a respiration capacity
of 20 breaths/min. During the physical examination, clear bilateral lung
sounds were observed without extensive dry or wet rales. No abnormal
findings were observed on the electrocardiogram (ECG) and
echocardiography. Head and neck skin cultures demonstrated the presence
of gram\selectlanguage{english}-positive \emph{Staphylococcus aureus} (3+) and \emph{Serratia
marcescens} (2+).

From day 2 to 6 after admission, the patient was provided four packed
red blood cells (PRBC) units with 2400 ml of frozen plasma (FP) due to
surgery, anemia, and severe wound exudation. No adverse effects occurred
during the transfusion, and arterial blood gas analysis indicated 99.8\%
arterial oxygen saturation (SpO\textsubscript{2}), 130 mmHg partial
pressure oxygen (PaO\textsubscript{2}), and 43.9 mmHg carbon dioxide
partial pressure (PaCO\textsubscript{2}).

On the seventh day of hospitalization, the patient suddenly developed
respiratory distress, dyspnea, and severe hypoxemia after receiving
approximately 100 ml of FP (SpO\textsubscript{2} 64.1\%;
PaO\textsubscript{2} 33.8 mmHg; PaCO\textsubscript{2} 39.6 mmHg). The
plasma transfusion was immediately discontinued, and the patient was
treated with facemask oxygen at 60L/min. Additionally, he was
intravenously administered 5mg dexamethasone due to suspected allergic
transfusion reactions. However, the hypoxic symptoms did not improve.
Coarse breathing sounds could be heard in the bilateral lungs upon
auscultation, and a chest radiograph suggested bilateral pulmonary
infiltrates. A heart rate of 136 beats/min was observed through an
urgent echocardiogram, with the ventricle and atrium presenting a
regular silhouette. The patient was intubated, mechanically ventilated,
and subsequently transferred to the intensive care unit (ICU) because of
worsening conditions. Ventilator settings were adjusted to synchronous
intermittent mandatory ventilation (SIMV) mode using 10 cm
H\textsubscript{2}O positive end-expiratory pressure (PEEP) and a 90\%
fraction of inspired oxygen (FiO\textsubscript{2}). After three days of
oxygen support, the patient's condition gradually improved, and
PaO\textsubscript{2} level became normal. He was transferred to the burn
and orthopedics department to treat the infected wound. FIGURE 1 depicts
the lung imaging.

We conducted high-resolution HLA genotyping to determine if TRALI was
developed. The HLA type of the recipient was identified as HLA-A* 24:02,
30:01; HLA-B* 13:02, 35:03; HLA-C* 06:02, 12:03; DRB1* 07:01, 07:01;
DQB1* 02:02, 03:03; and DPB1* 04:01, 13:01. The recipient had received
blood transfusions from a female plasma donor. The specific antibodies
HLA-DRB1* 07:01 (MFI 17322) and HLA-DQB1*02:02 (MFI 1366-1475) could be
detected upon testing in donor plasma and considered responsible for
TRALI development. This TRALI version, characterized by the two
antibodies, was not previously reported in China.

According to the symptoms and clinical course of the patient, this case
satisfies the TRALI Type I category of diagnostic
assessment.\textsuperscript{4} The case occurred within six hours of
blood transfusion; hypoxemia (SpO\textsubscript{2} \textless{}90\% on
room air); novel bilateral lung infiltrates could be observed on chest
radiography (Figure 1A and 1B); without any evidence of pulmonary
vascular overload or acute respiratory distress syndrome (ARDS) risk
factors.

\textbf{Discussion}

Most studies demonstrate that plasma donated by parous females is the
blood product commonly associated with TRALI. Several countries have
incorporated plasma from male donors to mitigate the risk of TRALI. The
blood donor, in this case, was identified as female. Still, her
fertility and transfusion history were unknown, preventing additional
clarification of her in vivo HLA antibody sources. She had donated blood
six times without any transfusion adverse events other than this. This
could be due to insufficient TRALI awareness among clinicians and an
imperfect reporting system for such adverse reactions in China. A study
evaluating the clinical outcomes of TRALI in a Chinese population
revealed that 34.5\% (20 out of 58) led to death. Moreover, logistic
regression analysis indicated that misdiagnosis affected patient
outcomes.\textsuperscript{5} The primary factor behind the successful
recovery of this case could be attributed to the timely identification
and provision of effective oxygen therapy by the clinician coupled with
supportive care. Therefore, improving TRALI awareness among clinicians
would ensure the well-being of patients. The diagnosis and management of
TRALI still need to be fully developed in China. Consequently, several
proactive measures should be implemented to minimize the occurrence and
mortality rates associated with TRALI.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Donelan KJ, Anderson KA. Transfusion-related acute lung injury
  (TRALI): a case report and literature review. \emph{S D
  Med.}2011;64(3):85-88. PMID: 21473518.
\item
  Politis C, Wiersum JC, Richardson C, et al. The International
  Haemovigilance Network Database for the Surveillance of Adverse
  Reactions and Events in Donors and Recipients of Blood Components:
  technical issues and results. \emph{Vox Sang.} 2016;111(4):409-417.
  doi: 10.1111/vox.12447.
\item
  Vlaar AP, Binnekade JM, Prins D, et al. Risk factors and outcome of
  transfusion-related acute lung injury in the critically ill: a nested
  case-control study. \emph{Crit Care Med.} 2010;38(3):771-778. doi:
  10.1097/CCM.0b013e3181cc4d4b.
\item
  Vlaar APJ, Toy P, Fung M, et al. A consensus redefinition of
  transfusion-related acute lung injury.
  \emph{Transfusion.}2019;59(7):2465-2476. doi: 10.1111/trf.15311.
\item
  Liu XM, Jiang Y, Liu JT, et al. Retrospective analysis of 58 cases of
  transfusion-related acute lung injury in Chinese population.\emph{Chin
  J Blood Transfusion.} 2020;33(8):780-783. doi:
  10.13303/j.cjbt.issn.1004-549x.2020.08.011.
\end{enumerate}

\textbf{Figure Legends}

\textbf{Figure 1} .

Lung images. \textbf{A} : Chest X-ray about 1 hour after transfusion:
bilateral lung infiltrates, bilateral pulmonary edema, and cardiac
shadow with standard size and normal morphology. \textbf{B} : chest
computed tomography (CT) 22 days after transfusion: Obvious absorption
of bilateral lung infiltrates.

\textbf{Hosted file}

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