Interesting Case Conference Brian C. Radlinski, MD January 27, 2015

Clinical History 43 y/o white F with SLE ESRD on HD CAD: MI and stents x 2 MR s/p MVR in 7/2013 AICD placement in 9/2014 Met. Multifocal PTC s/p thyroid resection in 10/2014 Chronic anemia: PCV 20-30% past 5+ yrs. 2 children, born in 2000 and 2002 Stents in 2002 and ‘12 50 LN mets

Clinical History MSSA bacteremia in Nov.; removal of Vascath; tx. With cefazolin x 4 weeks; new tunneled L. subclavian line on 12/5 Presented to OSH on 12/10 with fever; MSSA bacteremia again; transferred to VUH on 12/12 AICD extracted on 12/15 and cefazolin restarted x 6 weeks; removal of tunneled line on 12/16; discharged on 12/23

Prior Tx. Hx. and Blood Bank Reports Positive DAT for IgG fixation with negative eluate since 2009 Never evidence of immune hemolysis 2 RBC units 7/2010 2 RBC units 8/2010; last negative Ab screen 3/2013: Fya Ab (plus DAT+); 2 RBC units thereafter 7/2013: E Ab (plus Fya Ab and DAT+); partial phenotype: C Ag+, E Ag-, Jka Ag-; 2 RBC units thereafter 1 RBC unit 10/9/14 11/15/14: Jka Ab (plus E Ab, Fya Ab, and DAT+); partial phenotype: Jka Ag-; 1 RBC unit thereafter negative eluate (including on LISS) DAT always 2+ 3/2013: prior to L. knee I and D (infected hardware) 7/2013: prior to MVR 10/14: 3 days post-op thyroidectomy 11/2014: first adm. For MSSA bac.

Blood Bank Report – 12/15/14 H/o alloantibodies against Fya, E, and Jka; rec’d RBC tx.’s on 10/9/14 and 11/5/14 ABO type: A+ Ab Screen+, DAT 2+ for IgG and negative for complement Anti-s Ab identified in patient's plasma and the eluate Pt.'s RBCs previously tested by ARC and found to be s Ag- New clinically significant IgG antibody directed against the s antigen. This is consistent with a delayed serologic transfusion reaction

Delayed Transfusion Rxn. (DTR) Delayed hemolytic transfusion reaction (DHTR) Hemolysis occurs 24 hours to 28 days after transfusion (CDC) Anamnestic response: Exposure to non-self RBC Ag  Ab formation but fades over time (if pt. not retested after tx., might never be known)  re-exposure to Ag in future tx. (because Ab screen is negative)  Anamnestic rapid production of IgG Ab vs. target Ag IgG Ab remove RBC in the liver/spleen = extravascular hemolysis NB: DHTRs due to Jk Ab may be intravascular and severe (can fix complement)

Delayed Transfusion Rxn. (DTR) Sg/sx: fever, mild jaundice/scleral icterus, back pain, hypotension, etc. Lab findings: anemia, elevated LDH and (indirect±direct) bilirubin, decreased haptoglobin (even though extravascular), (micro)spherocytes on peripheral smear, DAT+ (classically “mixed field”), newly identified allo-Ab Treatment: Often unnecessary (unless severe and intravascular, then treat as for an acute HTR)

Delayed Transfusion Rxn. (DTR) Delayed serologic transfusion reaction (DSTR) Presence of a new, clinically significant RBC Ab in a patient transfused between 24 hours and 28 days ago without evidence of that Ab at time of tx., AND Complete lack of evidence of hemolysis Don’t diagnose DSTR without studying the patient carefully i.e., repeat Ab screen on pretransfusion sample if possible, evaluate bilirubin, haptoglobin, LDH, peripheral smear, etc. Blood group Ab associated with DTRs include Kidd, Duffy, Kell, and MNS, in order of decreasing frequency

Antigens of Pt.’s Alloantibodies Prev. Chrom. System HDFN? HTR? Dosage Enzyme modifi-cation Fya 65% (W) 10% (B) 1 Duffy yes ↓ E 30% (W) 21% (B) Rh Rare, mild ↑ Jka 77% (W) 91% (B) 18 Kidd s (little) 89% (W) 97% (B) 4 MNS Modern BB and Tx. practices

Donor Unit Compatibility This pt. has acquired Ab against Jka, E, Fya, and s. The probability of finding a donor unit negative for these Ag: 0.35 x 0.70 x 0.23 x 0.11 x 100 = 0.62% But pt. is A+, so can only receive A or O blood, which is 40% + 45% = 85% of donor population This decreases donor population to 85% of 0.62%, or 0.53% (or just 0.25% if matched for type A) Thus, number of units to crossmatch to find compatible unit: 1/0.0053 = 190 units, or 1/0.0025 = 403 units Pt.’s RBCs have been phenotyped at ARC; clinicians aware that if transfusion anticipated, as much advance notice as possible is needed

Questions/Comments

References Centers for Disease Control and Prevention. National Healthcare Safety Network: Biovigilance Component Protocol. August 2014. http://www.cdc.gov/nhsn/PDFs/Biovigilance/BV-HV-protocol-current.pdf Chaffin, J. Blood Bank Guy. Last updated 2015. www.bbguy.org Harmening, DM. Modern Blood Banking and Transfusion Practices. 5th ed. Philadelphia: F.A. Davis Company, 2005. Roback, JD et al. Technical Manual. 17th ed. AABB, 2011.