Transfusion-Associated Sepsis

Transfusion associated sepsis is sepsis caused by bacterial contamination of a blood component. It is the infection risk of transfusion with the highest fatality, and it should be suspected whenever fever, rigors or hypotension develop during or soon after transfusion.

Epidemiology. Platelet concentrates carry the highest risk because they are stored at room temperature (20 to 24 °C) for up to 5 to 7 days. Culture positive platelets are found in roughly 1 in 2,000 to 1 in 5,000 units without screening, and clinically significant sepsis occurs in about 1 in 25,000 to 1 in 100,000 platelet transfusions. Red cell contamination is rarer (about 1 in 500,000 or fewer).

Organisms. Platelets: skin flora (coagulase negative staphylococci, Staphylococcus aureus, Bacillus species, Streptococcus species) and enteric Gram negative bacilli (Klebsiella, Serratia, Escherichia coli). Red cells (cold stored): Yersinia enterocolitica, Serratia, Pseudomonas and other cold growing Gram negative bacilli, which carry endotoxin.

Sources. Donor bacteraemia (asymptomatic), skin contamination at venepuncture, and processing or equipment contamination.

Pathophysiology. Bacteria and endotoxin, introduced directly into the bloodstream with a large inoculum, cause rapid onset septic shock, DIC and multi-organ failure. Gram negative contamination causes more severe and earlier reactions.

Presentation is fever (38 °C or more with a rise of 2 °C or more), rigors, tachycardia, hypotension, nausea and vomiting, dyspnoea, abdominal pain and collapse, usually during transfusion or within 4 hours (occasionally up to 24 hours). Septic shock, DIC and renal failure may follow quickly.

Red flags.

• Rigors with hypotension during platelet or red cell transfusion.
• Fever in a patient who is neutropenic.
• Discoloured or clotted component, or a bag with absent swirling.

Stop the transfusion at once and keep the bag and giving set. Check the identity of the patient and product. Take blood cultures from the patient (aerobic and anaerobic, including from any central line) before antibiotics, and culture the bag content with Gram stain, the giving set and the co-components from the same donation. Send full blood count, coagulation, creatinine, lactate, haemolysis tests (direct antiglobulin test, plasma haemoglobin, haptoglobin, bilirubin) and a repeat crossmatch. Retain donor samples and trace other recipients.

Differential diagnosis. Febrile non-haemolytic reaction, acute haemolytic reaction, transfusion related acute lung injury, anaphylaxis, underlying sepsis, drug fever and transfusion associated circulatory overload.

Immediate. Stop transfusion, keep IV access with 0.9% sodium chloride, give oxygen, and call for senior help. Treat any febrile reaction with possible sepsis as sepsis until proven otherwise.

Antibiotics within 1 hour (after cultures).

• Piperacillin-tazobactam 4.5 g IV every 6 hours (adjust to renal function) plus vancomycin 25 to 30 mg/kg IV loading dose then 15 to 20 mg/kg every 8 to 12 hours (adjusted to level and renal function).
• Meropenem 1 g IV every 8 hours is an alternative for Gram negative cover, particularly with suspected Yersinia or resistant organisms.
• Adjust once organisms are identified and continue for 7 to 14 days, depending on organism and complications.

Resuscitation. Crystalloid 30 mL/kg for hypotension, then noradrenaline 0.05 to 1 microgram/kg/min to keep mean arterial pressure at least 65 mmHg. Correct DIC with platelets, plasma and cryoprecipitate as bleeding dictates.

Organ support. Ventilation, renal replacement and intensive care as needed.

Reporting and trace back. Notify the transfusion service and blood supplier immediately, quarantine co-components, and trace other recipients.

Prevention. Bacterial screening of platelets, pathogen reduction, diversion of the first volume of donor blood, skin disinfection, visual inspection before issue, and limits to storage time and time out of controlled storage (red cells to be completed within 4 hours of removal from storage).

Monitoring. Observations every 15 minutes initially, lactate, coagulation, creatinine and cultures.

Referral and escalation. Intensive care, haematology and infection specialists, with transfusion medicine input.

Special groups. In neutropenic and immunosuppressed patients, a low threshold to broaden antimicrobial cover (add antifungal if prolonged). In neonates and children, doses are weight based.