Transfusion-Related Acute Lung Injury due to Iatrogenic IVIG Overdose in Guillain-Barre Syndrome.

Transfusion-related acute lung injury (TRALI) is a transfusion-related adverse effect associated with high mortality, manifesting with acute respiratory distress and with features of non-cardiogenic pulmonary edema. It is rarely reported following intravenous immunoglobulin (IVIG) infusion and is even rarer in pediatric population. We here present a 12-year-old female child who presented as a case of acute flaccid paralysis and was diagnosed clinically as Guillain-Barre syndrome. As per protocol, she was given IVIG for 4 of the 5 days therapy at the dose of 0.4mg/kg/day before the patient went to another hospital. Subsequently in the next 1 week, she received two more courses of IVIG in two different hospitals following which she developed respiratory distress and was again admitted in our hospital. A diagnosis of TRALI was leveled on clinical ground because of IVIG overdose. Patient subsequently improved on high-flow oxygen therapy and conservative management. This unfortunate case of iatrogenic IVIG overdose just reinforces the fact of proper documentation of treatment to avoid such mishap and also prompt diagnosis and management of this least recognized entity of TRALI. Copyright:

Background

Transfusion-related acute lung injury (TRALI) is a transfusion-related adverse effect associated with high mortality, manifesting with acute respiratory distress and with features of non-cardiogenic pulmonary edema and is the major cause of blood transfusion–related death. Though rarely reported with intravenous immunoglobulin (IVIG) therapy, with wider use of IVIG in many conditions including Guillain-Barre syndrome (GBS), immune thrombocytopenia, and Kawasaki, there are now few reports of TRALI associated with infusion of IVIG. It is even rarely reported in pediatric population, and pathogenesis of its causation is also not clear till date. We here report a case of TRALI in an adolescent female child following iatrogenic overdose of IVIG.

Case Report

A 12-year-old female child came to our emergency department with complaints of gradually progressive weakness of bilateral lower limb and difficulty in walking for 4 days. On examination, the child was conscious and oriented with a lower limb power of 2/5 and generalized areflexia. Upper limb power was 4/5 and there was no cranial nerve involvement. A provisional diagnosis of GBS was made while stool samples for polio were also sent. Since the day of admission, patient was noticed to have early respiratory muscle weakness in the form of paradoxical chest wall movement. IVIG was started on clinical ground at a dose of 0.4g/kg/day for 5 days, but on the fourth day of admission the patient left against medical advice to another health facility. Till that time, she was stable and was maintaining vitals on oxygen despite some respiratory muscle weakness. Investigations at admission included complete blood count, liver function test, kidney function test and the results were found to be normal. Chest x-ray at admission was also essentially normal. Stool sample was negative for polio virus. After 6 days after leaving our hospital, she was again brought to our facility. This time she was not having paradoxical respiration but had complaints of respiratory difficulty of 2 days’ duration with marked tachypnea and hypoxia. On taking detailed history, it was revealed that after they went to another tertiary care hospital, she was again given three daily doses of IVIG despite transfer summary from our hospital had details of IVIG treatment and was subsequently referred to other hospital as ventilator support was not available for the patient. Unfortunately, again in the private nursing home she received full dose of IVIG. So as per our calculation, she received 5.2g/kg of IVIG, which exceeds far from the normal therapeutic dose of IVIG in GBS. On examination, chest was full of crepitations bilaterally. Chest x-ray had ill-defined opacities in bilateral lung field with no cardiomegaly whereas arterial blood gas showed compensated respiratory acidosis. So on the basis of the clinical scenario and investigations, we made a presumptive diagnosis of TRALI. Broad-spectrum antibiotic was started; she was kept on high-flow oxygen through face mask and intravenous fluid. After 48h, patient showed improvement clinically and radiologically. Echocardiography did not reveal any abnormality and blood cultures were also sterile. She could be gradually weaned from oxygen by day 5. She was treated with 14 days of antibiotic therapy. She is under regular follow-up after discharge and completely asymptomatic at present with no neurological deficit or respiratory morbidity.

Discussion

TRALI is a well-recognized complication of blood component therapy. Though rare with IVIG transfusion, there are reports of TRALI after IVIG overdose or rapid infusion. As there is no diagnostic parameter to diagnose TRALI, it is often not recognized and may be identified as a feature of pneumonia or septicemia.

IVIG is prepared from pooled blood of large numbers of healthy individuals. IgG is the main component of immunoglobulin, but it also contains small amounts of IgA and varying amount of other materials such as maltose and sucrose.[1] A high concentration of IgA and anti-Rh blood group D antigen (RhD) increases the occurrence of immunoglobulin-related adverse effects. Manlhiot et al.[2] found that adverse effects were reported more often in patients treated with immunoglobulin products that contained a concentration of IgA higher than 15 µg/mL.

TRALI is a transfusion-related adverse effect with high mortality, manifesting with acute respiratory distress and non-cardiogenic pulmonary edema within 6h of transfusion and is one of the main causes of blood transfusion–related death. In 2001, Rizk et al.[3] reported a 23-year-old male patient with motor neuropathy who developed TRALI following IVIG therapy; the patient’s condition resolved in 5days with only nasal oxygen and bed rest. In 2008, Berger-Achituv et al.[4] presented an adolescent patient with immune thrombocytopenia who developed TRALI during immunoglobulin infusion.

Diagnosing TRALI depends mainly on clinical symptoms that develop after blood products are infused in the absence of other evident causes of respiratory insufficiency; a chest x-ray that shows diffuse bilateral pulmonary edema is also needed.[5] Patients with TRALI often require adjuvant ventilatory support and will recover with proper ventilation.

TRALI is one of the leading causes of transfusion-related fatalities. Clinically, TRALI resembles acute respiratory distress syndrome—the underlying pathogenic mechanisms are, however, essentially different—and is associated with diffuse pulmonary edema, hypoxemia, and hypotension.[67] The pathophysiology of TRALI is complex and incompletely understood, although mouse models have contributed to the knowledge of the disease mechanism.[89] TRALI can be either antibody mediated (HLA class I or II) or antihuman neutrophil antigen (HNA antibodies) and non-antibody mediated.[10]

In our case, this complication of TRALI was completely avoidable with proper communication and documentation. Clinician using IVIG should be sensitized to closely monitor patients to pick up this potential fatal complication at the earliest and institute appropriate supportive care as required.

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Conflicts of interest

There are no conflicts of interest.