Yersinia septic shock following an autologous transfusion in a pediatric patient☆

1. Introduction 

Transfusion of blood during or following surgery or trauma and as a therapeutic modality for severely anemic patients is routinely provided. In 1999, an estimated 4.5 million patients received blood transfusions [1]. In many instances, the use of homologous blood cannot be avoided, as the need for blood is unanticipated. In some cases, however, blood loss and the requirement of a blood transfusion is anticipated and arrangements can be made for a patient to receive own blood.

Autologous blood transfusion is the term used to describe the transfusion of blood that has been previously donated by the intended recipient of the blood. Autologous transfusions are an option when a healthy person undergoes an elective procedure and the likelihood of receiving a blood transfusion is high. Orthopedic procedures such as total hip or knee replacement and scoliosis often qualify for autologous blood transfusions. Potential complications, such as alloimmunization with red blood cells, white cells and platelets can be avoided with autologous blood transfusion. However, the potential for transmission of infectious disease still exists. Prospective studies of autologous blood donation in scoliosis surgery have shown to be without significant complications in both adult and pediatric patients [2], [3]. One prospective study of 52 patients (ages 10–49 years) found that all eligible patients qualifying for autologous blood transfusions donated blood for future use in spinal fusion surgeries. Of these patients, 51 received blood transfusion during the procedure and only eight required additional homologous blood. No adverse events were reported [2]. Another prospective study of 50 adolescent patients, ages 11–18, evaluated the need for homologous blood required after autologous blood donations. With the combination of intra/post-operatively salvaged blood and autologous units of blood, homologous blood transfusions were not required. No adverse reactions attributed to the blood transfusions occurred [3]. Other studies reported a decrease in hospital infection rates, antibiotic usage and length of hospitalization with use of autologous donations rather than homologous donations. The studies, however, included surgeries other than scoliosis, had small sample sizes, and were retrospectively performed [4].

Between 1982 and 1992, the use of autologous blood transfusions has increased by 100% in pediatric patients [5]. Only one case of Yersinia enterocolitica transmission after an autologous blood transfusion has been reported in a pediatric patient [5].

In this case report, we present a pediatric patient who developed serious sequelae after receiving an autologous transfusion containing Y. enterocolitica. The patient developed severe sepsis, but recovered following a complicated hospital course. A greater than fourfold rise in the post-transfusion agglutinin titers suggested a recent repeat exposure to Y. enterocolitica.

2. Case report 

A 12-year-old, otherwise healthy female patient underwent a posterior spinal fusion of T1–T7 for congenital scoliosis. Prior to surgery, the patient donated four units of packed red blood cells (PRBCs) for possible transfusion during the procedure. A few days prior to the donation, the patient had a mild gastrointestinal illness. She was seen by a physician and was diagnosed with a viral illness. The patient reported feeling well during the donation process. During surgery, the patient experienced a 1500 ml blood loss, resulting in transfusion of the four units of autologous PRBCs. Near the completion of the procedure and immediately post-op, the patient developed fever up to 103.6 °F, became hypotensive, requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. It was initially believed the patient was experiencing malignant hyperthermia and attempts to cool the patient were made.

Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock and possible sepsis. On postoperative day (POD) 1, the patient’s condition worsened as she developed disseminated intravascular coagulation (DIC). The patient received supportive care and was started on ampicillin/sulbactam. These were changed to clindamycin, ciprofloxacin and tobramycin on POD 2 when blood cultures showed gram-negative bacilli. On POD 3, cultures were identified as Y. enterocolitica and antibiotic therapy was changed to tobramycin and cefotaxime based on the susceptibility data. The patient was treated with four weeks of tobramycin and cefotaxime after the first negative blood culture. Sequelae of the septic shock included adult respiratory distress syndrome (ARDS) requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required amputation of both feet. The cultures of the retained segments of the autologous red blood units yielded no growth. However, a greater than four-fold increase in the post-transfusion agglutinin titers suggested a recent repeat exposure to Y. enterocolitica. Isolates of the patient’s blood culture were serotyped as 0:3 by the Centers for Disease Control and Prevention (CDC).

3. Discussion 

The transfusion of Y. enterocolitica-infected autologous blood has been reported in only one pediatric patient and two adult patients (Table 1). This case report differs substantially from the other three reported cases. The other reported pediatric case was a 15-year-old male, also undergoing surgery for scoliosis. The patient had gastroenteritis and was febrile four days prior to donation of PRBCs. The diarrhea persisted throughout the donation period, although the fever subsided. The patient required two units of PRBCs during the surgery. Postoperatively, the patient also experienced shock, hypotension, renal failure and anemia. Antibiotic treatment consisted of cefotaxime and gentamicin initially, but eventually ceftriaxone and ciprofloxacin after culture results became available. The patient fully recovered after three months of antibiotic therapy. Y. enterocolitica serotype 0:3 was recovered from two blood cultures; however, cultures from the transfused blood were not available [6].

Table 1. Cases of Yersinia enterocolitica sepsis following autologous transfusion, their presentation, treatment, and clinical outcome

	Reference	Year	Age	Symptoms at donation	Symptoms after transfusion	Y. enterocolitica serotype	Antimicrobial treatment (duration of therapy)	Clinical outcome
	6	1992	74	Febrile at donation, GE three days later	Cyanotic, respiratory distress	0:3, + growth in donated blood	Imipenem (no dose given) (unknown duration)	Full recovery
	5	1993	15	Febrile and GE at donation	Febrile, hypotensive, tachycardic, oliguric	0:3, − growth in donated blood	Cefotaxime 1 g IV six times daily, gentamicin 90 mg IV BID (∼9 days), then ceftriaxone 2 grams QD and ciprofloxacin 200 mg BID (∼3 weeks), then ciprofloxacin 500 mg po BID (3 months)	Full recovery
	7	1994	64	No symptoms at donation, febrile and GE one week prior	Febrile, hypotensive, anemic, decreased renal function, leukocytosis	0:9, + growth in donated blood	Ceftriaxone and tobramycin added later in therapy (∼1 week) then doxycycline orally (no dose given) (1 month)	Full recovery
	Patient in this case report	2002	12	Asymptomatic at donation, GE few days prior to donation	Febrile, hypotensive, metabolic acidosis, disseminated intravascular coagulation	0:3, growth in donated blood	Clindamycin, tobramycin and ciprofloxacin (∼3 days) changed to tobramycin and cefotaxime (1 month)	Seizure disorder, bilateral BKA

GE=gastroenteritis; BKA=below the knee amputation.

In our patient, the gastroenteritis was believed to be viral in origin and the patient was not experiencing any signs or symptoms at the time of donation. Additionally, the onset of shock was more rapid and severe, possibly due to a larger inoculation of the bacteria. Because both pre- and post-transfusion blood samples demonstrated agglutinins, with a significant increase in the post-transfusion sample, it was determined that the sepsis resulted from the transfusion of the infected autologous blood donation.

Two other reported cases involved adult patients. One patient was a 74-year-old male who underwent a total knee replacement surgery. The patient was afebrile at the time of the donations, but reported diarrhea three days after the donation of blood. The patient became cyanotic and began experiencing respiratory distress as 100 ml of blood was transfused. The patient was treated with imipenem and fully recovered from the infection. The donated blood was cultured and was positive for Y. enterocolitica serotype 0:3 and had 3510 ng/ml of endotoxin [6]. The second adult patient required a total knee replacement and donated one unit of PRBCs. Immediately after the donation, the patient became ill and anemic. The patient was admitted to the hospital 33 days after the donation with a low red blood cell count and was transfused with the autologous donation. The patient received 150 ml of the PRBCs and immediately developed symptoms of shock including hypotension, renal failure and leukocytosis. The patient was treated successfully with ceftriaxone and tobramycin. The patient’s blood culture showed Y. enterocolitica. The remaining donated blood was also cultured and Y. enterocolitica serotype 0:9 was identified [7].

In each case, the patient donating the blood was ill, became ill or had a history of a recent illness. In three of the four cases, the patients had experienced some type of gastroenteritis. One case did not specify the type of illness the patient experienced. Our patient may have had gastroenteritis due to Yersinia, which seeded from the gastrointestinal tract and caused a transient bacteremia at the time of the donation. PRBCs are stored at a temperature of 1–4 °C, at which Yersinia is capable of surviving and replicating. In addition, the bacteria produce an endotoxin at temperatures less than 30 °C [8]. Based on the available literature, patients with recent history of or concurrent diarrhea may not be good candidates to donate blood for autologous transfusions. It is unknown after what period of time it may be safe to donate blood.

Patients receiving a transfusion must be closely monitored after the infusion for signs of a transfusion reaction, including possible sepsis. In cases of transfusion transmitted infections, initial symptoms may include fever, chills, hypotension, nausea, vomiting, diarrhea, oliguria, shock, respiratory symptoms and bleeding due to DIC. In our patient, and the other reported cases, the onset of symptoms occurred immediately following the transfusion.

Y. enterocolitica antimicrobial sensitivity is dependent on the serotype of the microorganism. Serotype 0:3 and 0:9 produce beta-lacatamases, which render them resistant to penicillins, aminopenicillins and the first-generation cephalosporins [9]. In vitro data of 350 isolates collected over a nine-year period found that Y. enterocolitica was susceptible to piperacillin, piperacillin/tazobactam, imipenem, ceftazadime, cefepime, aminoglycosides, quinolones and cotrimoxazole [10].

One retrospective study documented cases of Y. enterocolitica septicemia to evaluate the antibiotic treatment. The study included 53 cases with patients between the ages of 3–89 years old (mean 61 years). Of these cases, 43 were evaluated for antibiotic administration. The in-vitro antimicrobial sensitivities of the cultured microorganisms included third-generation cephalosporins, aztreonam, imipenem, aminoglycosides, tetracyclines, fluoroquinolones, ureidopenicillins, and trimethoprim-sulfamethoxazole. Treatment failure, defined as a fever or persistence of clinical symptoms, occurred in any patients receiving older penicillins (e.g. benzylpenicillin and amoxicillin) or when amoxicillin/clauvulanate was used alone. No cases in which fluoroquinolones were used failed therapy, even when the fluoroquinolone was used alone. The use of an aminoglycoside with a third-generation cephalosporin, the combination used in our patient, resulted in clinical success in 14 of the 17 patients (82.4%). The duration of therapy ranged from 2 to 6 weeks with a median of 22 days. Although this study was not designed to answer which antimicrobial regimen is most effective, it provided some data about which antibiotics may result in clinical failure [11].

Autologous blood transfusions can decrease the potential for transfusion transmitted infectious diseases, especially viral infections, and decreases the risk of alloimmunization to blood products. However, autologous blood transfusions, as with any transfusion, may cause bacterial infections. As noted in the cases, patients may be symptomatic or asymptomatic and may become bacteremic with Y. enterocolitica during the donation. Any patient receiving a transfusion who appears to be in shock should receive broad spectrum antibiotics (e.g., aminoglycosides and third-generation cephalosporin, as empiric treatment). Specific antibiotic treatment should be used when the culture and sensitivity data become available to achieve the desired clinical outcome.