Postoperative transfusion-related acute lung injury in a young woman with corpus luteum cyst rupture: Case report and literature review

Abstract

This case study examines a 22-year-old unmarried woman who experienced shock resulting from rupture of a corpus luteum cyst. During the perioperative period, the patient received multiple transfusions of red blood cells and fresh frozen plasma. Subsequently, the patient developed transfusion-related acute lung injury 6 h following the final blood transfusion. The findings indicated that the inflammatory characteristics of antiphospholipid syndrome and deep vein thrombosis were closely associated with the onset of transfusion-related acute lung injury. Surgical procedures and multiple perioperative blood transfusions, particularly those involving fresh frozen plasma, were identified as significant contributors to the acute onset of transfusion-related acute lung injury. It is crucial for healthcare professionals to improve blood transfusion management and increase awareness of transfusion-related acute lung injury, especially in African countries with limited medical resources.

Introduction

Transfusion-related acute lung injury (TRALI) is a clinical syndrome marked by the sudden onset of noncardiogenic pulmonary edema and hypoxemia, manifesting during or within 6 h following transfusion. In surgical patients receiving blood transfusions, the incidence of TRALI is reported to range from 1.3% to 1.4%. ¹ TRALI represents the leading cause of mortality linked to transfusion-related complications, with mortality rates estimated between 5% and 25%. ² However, among patients in intensive care and surgical settings, these rates have been observed to increase to as high as 47%. ³

A corpus luteum cyst is a functional ovarian structure characterized by fragile vasculature, which is prone to rupture, potentially resulting in intracystic hemorrhage, hemoperitoneum, and significant internal bleeding. ⁴ During transfusion, there is a risk of TRALI, a serious and potentially life-threatening complication associated with blood transfusion procedures. ⁵ Both TRALI and transfusion-associated circulatory overload (TACO) are characterized by the onset of respiratory distress in temporal association with transfusion. TRALI is further distinguished from acute respiratory distress syndrome (ARDS). However, the condition is frequently misdiagnosed, especially among patients in intensive care settings.^6,7

To our knowledge, this article documents the first reported case in Algeria of a patient who experienced ruptured luteal intraperitoneal hemorrhage and subsequently developed a more severe form of TRALI postoperatively. Increased awareness of TRALI may assist blood collection and processing services in devising strategies to further reduce the risk of TRALI and support the development of clinical approaches for its management.

Case report

A 22-year-old unmarried woman presented to the outpatient clinic at the Women and Children’s Hospital of Setif University in mid-February 2024, reporting acute pain in the right lower abdomen. All patient details have been de-identified. Laboratory investigations indicated a β-human chorionic gonadotropin (β-HCG) level of <0.5 mIU/mL. Hematologic analysis revealed a hemoglobin concentration of 7.8 g/dL, a platelet count of 243 × 10⁹/L, a white blood cell count of 21.2 × 10⁹/L, an international normalized ratio (INR) of 5.36, and a prothrombin time (PT) activity of 73%. Ultrasonographic examination identified an enlarged right ovary measuring 6.1 × 4.5 cm, accompanied by a substantial volume of intraperitoneal hemorrhage, suggestive of a probable corpus luteum cyst rupture (Figure 1(a) and (c)). No abnormalities were observed in the other abdominal organs (Figure 1(b) and (d); Figure S1). The patient was diagnosed with antiphospholipid syndrome (APS) in 2017 and had a history of two episodes of deep vein thrombosis (DVT). On 11 February 2024, the C-reactive protein (CRP) concentration was recorded at 46.05 mg/L. The concentration of complement component C3 was measured at 1.04 g/L, whereas the concentration of C4 was 0.33 g/L. The 24-h urinary protein excretion was recorded at 40.99 mg. An electrocardiogram (ECG) performed on 11 February demonstrated sinus rhythm accompanied by a completely right bundle branch block (Figure S2). On 12 February, a complete blood count revealed a leukocyte concentration of 10 × 10⁹/L, a hemoglobin (HGB) concentration of 12.5 g/dL, and a platelet (PLT) concentration of 177 × 10⁹/L. On 13 February, the erythrocyte sedimentation rate was measured at 40 mm at the end of the first hour and 70 mm at the end of the second hour. Prior to these assessments, the patient had been receiving oral administration of acenocoumarol.

Figure 1.

Ultrasound examination and intraoperative photograph: (a) The right ovary exhibited increased volume, measuring 6.1 × 4.5 cm, with mixed echogenic patterns (indicated by the red dotted circle). (b) The left ovary appeared normal, with no detectable abnormalities. (c) A significant accumulation of fluid was observed within the abdominal cavity (highlighted by the red dotted circle). (d) The uterus displayed normal size and morphology, with no apparent abnormalities within the uterine cavity. (e) A large amount of dark red blood had accumulated in the abdominal cavity.

Algerian physicians promptly initiated emergency medical intervention, advising the patient to discontinue oral administration of acenocoumarol. Subsequently, vitamin K injections were administered, and a transfusion of 400 mL of fresh frozen plasma was initiated at 09:00. Laboratory investigations conducted at this time revealed the following results: a hemoglobin level of 7.4 g/dL, a platelet count of 189 × 10⁹/L, and a white blood cell count of 9 × 10⁹/L. The patient’s INR was 1.23, and PT activity was 74%.

By 17:00, an additional 400 mL of fresh frozen plasma was being transfused. During this transfusion, the patient reported increased abdominal discomfort. Physical examination revealed abdominal distension accompanied by tenderness and rebound pain. Subsequent blood tests indicated the following results: a hemoglobin level of 7.9 g/dL, a platelet count of 152 × 10⁹/L, a white blood cell count of 10.6 × 10⁹/L, an INR of 1.51, and PT activity of 63.2%. In response to worsening hemorrhage resulting from rupture of the ovarian corpus luteum cyst, and the patient’s presentation with hemorrhagic shock—manifested by restlessness, pallor, cold extremities, and tachycardia—the medical team decided to perform emergency exploratory surgery without delay. Upon surgical entry into the abdominal cavity, a substantial accumulation of dark red blood and clots was observed (Figure 1(e)). Following partial fluid drainage, the right ovary was found to be markedly enlarged, measuring 8 × 7 cm, with an active 1 cm rupture. The corpus luteum was excised, and blood clots were evacuated prior to tissue suturing. Approximately 2000 mL of fluid was aspirated from the abdominal cavity, with no additional abnormalities noted. Intraoperatively, the patient received 600 mL of red blood cells, followed by an additional 400 mL of red blood cells and 600 mL of fresh frozen plasma postoperatively, with transfusion concluding by 03:00 on 17 February.

On 17 February at 08:00, the patient presented with chest pain and dyspnea. Vital signs revealed hypotension with a blood pressure of 90/60 mmHg, tachycardia with a heart rate of 123 bpm, tachypnea with a respiratory rate of 73 breaths per minute, and severe hypoxemia with an oxygen saturation of 63%. Immediate interventions were initiated to address hypoxemia and improve oxygenation. Electrocardiogram findings demonstrated abnormal T-wave patterns in leads III, AVF, V3, and V4. The patient’s breathing was shallow and rapid, and she exhibited apathy. Lung auscultation revealed pronounced bilateral rales. Given the acute nature of the patient’s condition, urgent intervention was necessary, leading the anesthesiologist to perform endotracheal intubation. Mechanical ventilation settings were established with an FiO₂ of 100%, a PEEP of 7 cm H₂O, a respiratory rate of 12 breaths per minute, and an inspiratory-to-expiratory ratio of 1:1.5.

Regrettably, neither arterial blood gas (ABG) analysis nor chest X-ray examination was conducted because the hospital lacked the capacity to perform ABG testing and echocardiography. Following intubation, the patient’s oxygen saturation returned to near-normal levels, and symptoms improved significantly within 1 h. The respiratory rate rapidly decreased to 15 breaths per minute, and the heart rate decreased to 113 beats per minute. Laboratory analyses revealed a hemoglobin concentration of 11.4 g/dL, a platelet count of 171 × 10⁹/L, and a white blood cell count of 24.2 × 10⁹/L. Notably, the levels of granulocytes (GRA) and GRA (%) increased substantially, reaching 21.9 × 10⁹/L and 89.8%, respectively. Concurrently, the concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), CRP, lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), and D-dimer were recorded at 73.79 IU/L, 52.76 IU/L, 165.4 mg/L, 480 U/L, 3176 pg/mL, and 3.43 mg/L, respectively (Table 1 and Figure 2). Postoperatively, only 50 mL of peritoneal fluid was drained.

Table 1.

Laboratory investigation results during the perioperative period.

Items	Reference range	16 February			17 February	19 February	21 February
		00:27	8:52	15:04	8:00	9:16	10:45
HGB (g/dL)	11.5–16.5	7.8	7.4	7.9	11.4	11.7	13.7
PLT (×109/L)	130–400	243	189	152	171	161	144
WBC (109/L)	3.5–10	21.2	9	10.6	24.2	11.1	8.7
GRA (×109/L)	1.2–8	18.2	7.6	8.1	21.9	8.8	6.2
GRA (%)	35–80	85.2	82.8	76.7	89.8	78.6	71
PT (%)	70–100	73	74	63.2	–	84	–
INR	0.98–1.2	5.36	1.23	1.51	–	–	–
β-HCG (MUI/mL)	<5	<0.5	–	–	–	–	–
CREA (mg/L)	5–12	–	–	–	5.66	6.35	5.01
Calcium (mg/L)	86–100	–	–	–	2.93	95	–
Glucose (g/L)	0.74–1.09	–	–	–	1.14	0.98	1.15
Urea (g/L)	0.16–0.48	–	–	–	0.35	0.52	0.2
Na+ (mg/L)	135–145	–	–	–	137	138	136
K+ (mg/L)	3.5–5.5	–	–	–	3.8	3.4	3.5
Troponin (ng/L)	<14	–	–	–	7033	–	–
AST (IU/L)	10–32	–	–	–	73.79	42.4	–
ALT (IU/L)	5–33	–	–	–	52.76	18.2	–
TBIL (mg/L)	0.1–12	–	–	–	18.73	–	–
DBIL (mg/L)	<3	–	–	–	7.28	–	–
IBIL (mg/L)	<7	–	–	–	11.45	–	–
CRP (mg/L)	0–18	–	–	–	165.4	–	–
LDH (U/L)	135–225	–	–	–	480	–	–
BNP (pg/mL)	<100	–	–	–	3176	–	–
D-dimer (mg/L)	<0.5	–	–	–	3.43	–	–

ALT: alanine aminotransferase; AST: aspartate aminotransferase; BNP: brain natriuretic peptide; CREA: creatinine; CRP: c-reactive protein; DBIL: direct bilirubin; GRA: granulocytes; HGB: hemoglobin; IBIL: indirect bilirubin; INR: international normalized ratio; LDH: lactate dehydrogenase; PLT: platelet; PT: prothrombin time; TBIL: total bilirubin; WBC: white blood cell; β-HCG: chorionic gonadotropin beta.

Figure 2.

The patient's blood test results were monitored throughout the treatment process. Following rupture of the corpus luteum, elevated levels of white blood cells, granulocytes, and granulocyte percentage were observed. These levels showed a declining trend after initiation of active treatment. With increasing blood transfusion volume and the impact of surgical intervention, these values increased markedly, peaking at 9:46 on the first postoperative day (a, b). Hemoglobin levels demonstrated an upward trend in response to blood transfusion and surgical treatment (c), whereas platelet levels exhibited an inverse trend (d).

Abdominal ultrasonography revealed no significant abnormalities. A CT scan of the lungs ruled out pulmonary embolism but identified ground-glass opacities affecting 75% of the lung parenchyma, likely attributable to a recent SARS-CoV-2 infection. A throat swab test yielded negative results for the virus. Based on the patient’s medical history and diagnostic findings, clinicians hypothesized that the patient was experiencing pulmonary inflammation potentially induced by TRALI. Following extubation on the second day, the patient’s blood oxygen saturation and body temperature normalized. The patient was discharged after 9 days of symptomatic supportive care, which included administration of furosemide, ciprofloxacin, cefazolin, enoxaparin, and midazolam, among other treatments. The detailed treatment regimen is systematically outlined in the timeline (Figure S3). The patient was advised to attend a follow-up appointment at the outpatient clinic 2 weeks postdischarge. Unfortunately, she did not attend the scheduled follow-up. Reporting of this study adhered to the Case Report (CARE) guidelines. ⁸

Discussion

According to the current literature, this study is the first to document that patients with APS and DVT who experience hemorrhage from a ruptured ovarian corpus luteum may develop acute TRALI within 6 h following transfusion. Prompt and effective intervention facilitated the patient’s rapid recovery, thereby averting potential adverse outcomes.

The term “TRALI” was introduced by Popovsky, who estimated its incidence to be approximately 0.16% among transfused patients. ⁹ In 2019, a novel diagnostic criterion was established using the Delphi method, effectively categorizing TRALI into Type I and Type II. ¹⁰ It is important to acknowledge that distinguishing TRALI from TACO is inherently challenging, necessitating comprehensive examinations to establish a definitive diagnosis.

As illustrated in this case, the patient exhibited no evidence of risk factors for ARDS or left atrial hypertension. However, the patient developed hypoxemia and bilateral pulmonary edema within 6 h following blood transfusion. The patient’s medical history included APS and two episodes of lower-extremity DVT, which may have been associated with TRALI. Limitations in the hospital’s medical facilities precluded the performance of blood gas analysis and echocardiography, thereby restricting our ability to provide detailed data on PaO₂, FiO₂, and echocardiographic findings. Clinically, the patient presented with diffuse bilateral wet rales in the absence of pink frothy sputum and required mechanical ventilation. Notably, the patient’s blood pressure was low rather than elevated. Symptoms gradually resolved over a period of 96 h. Based on the clinical presentation and disease course, TRALI was considered the most likely diagnosis for this patient.

The precise etiology of TRALI remains incompletely understood, although it is associated with multiple factors. A prominent hypothesis is the “two-hit” mechanism, whereby inflammatory responses prime neutrophils and other cells, rendering critically ill and injured patients more susceptible to TRALI. Research has identified host-related risk factors as pro-inflammatory agents that activate pulmonary neutrophils, constituting the initial “first hit” in the pathogenesis of TRALI. ¹¹ Subsequent blood transfusion is considered the second hit.

Blood products with high plasma content are associated with an increased incidence of TRALI. ¹² The patient described in this report exhibited several high-risk factors consistent with the “two-hit” hypothesis. These included acute massive hemorrhage resulting from luteal rupture, physical trauma, repeated blood transfusions with substantial plasma volumes, and systemic inflammatory lesions. Because of the hospital’s limited resources, comprehensive examinations could not be performed, precluding the assessment of additional inflammatory markers. Owing to the hospital’s inability to independently test neutrophils, our analysis was limited to GRA, along with granulocyte percentage and white blood cell count. Figure 2 illustrates that these three indicators exhibited two peaks, with the second peak occurring post-blood transfusion and surgery and reaching the highest values. This observation is consistent with the “two-hit” pathogenesis of TRALI. Concentrations of AST, ALT, CRP, LDH, BNP, and D-dimer were significantly elevated, suggesting that TRALI may induce acute hepatic and cardiac injury. TRALI often occurs following transfusion of plasma-rich blood products containing anti-HLA or anti-HNA antibodies. It may also occur when recipients possess antibodies that react with donor leukocyte antigens. ¹³

Upon onset of TRALI, it is crucial to immediately discontinue blood transfusion and intensify monitoring and fluid restriction. Standard supportive treatment strategies include administration of supplemental oxygen, mechanical ventilation with low tidal volumes, and meticulous fluid management to prevent volume overload. ¹⁴ Many researchers advocate that plasma and whole blood products should be sourced from male donors, nonpregnant female donors, or female donors with prior pregnancies who have repeatedly tested negative for HLA antibodies. ¹⁵ A meta-analysis indicated that excluding female blood donors resulted in a 73% reduction in the incidence of plasma transfusion-associated TRALI. ¹⁶

This study has several limitations. The hospital’s limited resources precluded performance of certain diagnostic tests, such as blood gas analysis and echocardiography. In addition, the patient did not return for follow-up after discharge, preventing collection of data regarding the recovery trajectory.

This study suggests that APS and DVT may be potential contributing factors for TRALI. These factors, in conjunction with acute blood loss and multiple transfusions, particularly fresh frozen plasma transfusion, may contribute to the development of TRALI. In some African countries with limited medical resources, clinicians should further increase awareness of TRALI.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605261452582 - Supplemental material for Postoperative transfusion-related acute lung injury in a young woman with corpus luteum cyst rupture: Case report and literature review

Supplemental material, sj-pdf-1-imr-10.1177_03000605261452582 for Postoperative transfusion-related acute lung injury in a young woman with corpus luteum cyst rupture: Case report and literature review by Juan Wang, Shengyu Yang, Hua Cao, Berchi Khaoula and Ronghua Liu in Journal of International Medical Research