Transfusion medicine

• Transfusion transmitted bacterial infections (TTBI) present with fever, chills and hypotension immediately or up to 24 hours after a transfusion
• Platelets are by far the most commonly bacterially contaminated blood component due to room temperature storage and TTBI is one of the leading causes of death due to transfusion each year
• Bacterial risk control strategies for platelets include donor testing for bacteria and pathogen reduction technology (PRT)

• Note that pathogen reduction technology does not require bacterial testing (screening)
• Permissible risk control strategies using FDA approved methods are outlined below with some useful naming codes in parentheses:
  • Apheresis platelets or prestorage pools of whole blood derived platelets
    • Single step methods:
      • Primary culture no sooner than 24 hours, 3 day shelf life (24C-3)
      • Large volume delayed sampling at 36 hours postcollection, 5 day shelf life (36C-5)
      • Large volume delayed sampling at 48 hours, 7 day shelf life (48C-7)
      • Pathogen reduction technology, 5 day shelf life (PRT)
    • 2 step methods:
      • Primary culture no sooner than 24 hours with secondary culture performed no sooner than day 3, 5 day shelf life (24C-D3C-5)
      • Primary culture no sooner than 24 hours with secondary culture no sooner than day 4, 7 day shelf life (24C-D4C-7)
      • Primary culture no sooner than 24 hours with rapid testing, 5 day shelf life (24C-R-5)
      • Primary culture no sooner than 24 hours with rapid testing, 7 day shelf life (24C-R-7)
      • Large volume delayed sampling no sooner than 36 hours with secondary culture no sooner than day 4, 7 day shelf life (36C-D4C-7)
      • Large volume delayed sampling no sooner than 36 hours with secondary rapid testing, 7 day shelf life (36C-R-7)
  • Single units and poststorage pools of whole blood derived platelets
    • Rapid testing for 5 day shelf life of single units and 4 hours after pooling for poststorage pools of whole blood derived platelets
    • Single culture with sampling performed no sooner than 36 hours after collection with a 5 day shelf life
    • Single culture with sampling performed no sooner than 24 hours after collection for 5 day shelf life, if transfused after day 3 of storage, secondary rapid testing may be considered (FDA-2014-D-1814) (FDA: Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion [Accessed 8 June 2020])

List of permissible bacterial risk control testing policies for apheresis platelets and their characteristics
Policy code	Primary culture		Component expiration time (hours)	Secondary test			Availability (hours)
	Sample time (hours)	Hold time (hours)		Test type	Sample time (hours)	Hold time (hours)
24C-3	24	12	72	N/A	N/A	N/A	36
36C-5	36	12	120	N/A	N/A	N/A	72
48C-7	48	12	168	N/A	N/A	N/A	108
24C-D3C-5	24	N/A	120	culture	72	*	72
24C-D4C-7	24	N/A	168	culture	96	12	120
36C-D4C-7	36	N/A	168	culture	96	12	108
24C-R-5	24	N/A	120	rapid	12 hours prior to issue	N/A	84
24C-R-7	24	N/A	168	rapid	12 hours prior to issue	N/A	132
36C-R-7	36	N/A	168	rapid	12 hours prior to issue	N/A	120

*Time period not specifically defined in FDA guidance; a hold period is required in the guidance but not specified for this testing policy (Walker BS et al. The comparative safety of bacterial risk control strategies for platelet components: A simulation study. Transfusion. Accepted.)

• False positive results are not uncommon
  • If bacterial testing is positive, recommend sampling the platelet bag for a confirmation culture
  • Organism should be identified and retrieval of any co-components is required
• Donor should be notified if bacteria not a likely skin contaminant
• Non-PRT strategies (i.e. those involving testing) have residual risk of contamination and septic transfusion reactions due to false negative results, which depends on strategy used and bacterial growth characteristics (Transfusion 2018;58:1647, Vox Sang 2012;103:1)
• Acinetobacter spp. and several other species have been reported as causing septic transfusion reactions in PRT and platelet additive solution products (FDA: Important Information for Blood Establishments and Transfusion Services Regarding Bacterial Contamination of Platelets for Transfusion [Accessed 11 March 2022])

A 65 year old man with a history of acute lymphoblastic leukemia is undergoing induction and has required multiple transfusions for anemia and thrombocytopenia. During a platelet transfusion, he develops fever, chills and hypotension. The transfusion is stopped and the product is returned to the Transfusion Service. Chest Xray shows no pulmonary edema or infiltrates. The Transfusion Service reports no hemolysis and the DAT is negative. What is the next most important step?

1. The patient should be given an antihistamine
2. The patient should be transferred to the ICU for close monitoring
3. The patient should receive an antipyretic medication
4. The patient's blood and the residual product should be cultured and the patient should be treated empirically with antibiotics
5. The product and any other products created from the same donation should be thrown away

D. The patient and the residual product should be cultured for aerobic and anaerobic bacteria. Additionally, a Gram stain should be performed to immediately provide clinicians a preliminary identification but are variably negative. If the cultures are positive, the organism should be the same. Additional testing, such as pulsed field gel electrophoresis of DNA macrorestriction, can lend information as to the similarities of the bacterial isolates. Since culture is a time intensive process, if there is clinical concern for a TTBI, the patient should be empirically treated with broad spectrum antibacterial coverage until identification with antibiotic sensitivities are available. While additional donor products should be identified and isolated, the products should be cultured, not thrown away. The ICU is likely necessary in a septic patient but further workup is still necessary for a diagnosis. The patient does not have symptoms solely suggestive of an allergic reaction, which would include urticarial, angioedema, bronchospasm, etc. An antipyrectic medication may be appropriate but the hypotension is concerning for a more serious transfusion reaction than a febrile, nonhemolytic reaction.

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Reference: Bacterial contamination of blood components

A donor presents to donate an apheresis platelet. The donor history questionnaire, vitals and hemoglobin / hematocrit are acceptable. The donor donates without incident. Viral testing returns negative. The product is cultured at 24 hours. According to the September 2019 FDA guidance, what is one permissible next step?

1. After the appropriate amount of hold time (12 hours), the product is ready for transfusion with a 7 day shelf life
2. After the appropriate hold period (12 hours), the product is ready for transfusion with a 4 day shelf life
3. Rapid testing may be used according to the manufacturer's package insert with up to a 7 day shelf life of the platelet product
4. Secondary culture cannot be used to extend shelf life

C. Rapid testing may be used according to the manufacturer's package insert with up to a 7 day shelf life of the platelet product. The product is an apheresis platelet with a primary culture performed at 24 hours, which without a subsequent secondary test, has a shelf life of 3 days. A secondary test may be used to extend the shelf life. These may include rapid testing or secondary culture no sooner than day 4 for up to a 7 day shelf life. These strategies are based on the September 2019 FDA Guidance, which has several permissible strategies that are outlined above in this chapter.

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Reference: Bacterial contamination of blood components