1. CP SERVICE REVIEW 4-5-2010 LMROC 3-29 TO 4-4 Nicole Cipriani

2. Saturday/Sunday  3 TTP patients  JB 59 year old male s/p liver transplant and HepC  microangiopathic hemolytic anemia Plts 53  72  92  RS 73 year old male angioimmunoblastic T cell lymphoma  confusion, multi-organ failure Plts 66  30  LM 29 year old female with chronic relapsing TTP  left sided weakness ADAMTS13 activity: 67%) ADAMTS13 inhibitor: 1.4 units (nml <0.4) Plts 8  17

3. Chronic Relapsing TTP  To be discussed May 24

4. Choose your adventure * Transfusion Reaction * Transfusion-related infectious disease

5. Case 1  13 year old male with history of hypertrophic obstructive cardiomyopathy  3-17-2010  ICD placement  Morrow procedure (resection of subaortic muscle)  Complicated by  Postoperative bleed  LV dysfunction  LVAD  Additional surgeries

6. Blood Products Received  44 units RBC  28 units FFP  9 packs Platelets  5 units Cryo  3-17 to 4-1

7. Transplant Candidate  HIV ELISA  Non-reactive  Hepatitis C virus antibody  Reactive x5 (3-28 to 4-2)  10 days prior nonreactive (3-18)  Hepatitis C viral load  None detected (3-30)  (Real time PCR for Hepatitis C RNA)  EBV IgG capsid antibody  Positive NO additional known risk factors for HCV. Test Blood Donors ?

9. Postgrad Med J. 1994 Aug;70(826):572-5. Prevalence of antibodies to hepatitis C virus after blood transfusion in heart surgery. Barcena R, Gonzalez A, Martin-de-Argila C, Ulibarrena C, Graus J, Grande LA. Department of Gastroenterology, Ramon y Cajal Hospital, Alcalá de Henares University, Madrid, Spain. We studied the frequency and time of appearance of antibodies to the hepatitis C virus (HCV) retrospectively in the sera of 127 patients who underwent heart surgery between 1983 and 1986. They received blood from volunteer donors hepatitis B surface antigen (HBsAg) negative with normal serum alanine-aminotransferase levels. A prospective follow-up was carried out every 15 days for at least 6 months from the moment of the transfusion. Of the ten patients who developed biochemical criteria of post-transfusional non-A non-B hepatitis, six seroconverted to anti-HCV (60%). Of the other 117, two were already positive before transfusion (1.51%), one patient showed antibodies only in the first post-transfusional serum (passive transfer), and another two patients with no evidence of post-transfusional hepatitis developed HCV antibodies on the 90th day, remaining indefinitely (afterwards seroconversion without hepatitis); both patients' earlier sera were anti-HCV negative. Four (40%) of the ten patients with post-transfusional hepatitis did not develop any serum markers to known hepatotropic agents. Although these findings do not exclude a viral infection by these viruses, they are consistent with the involvement of an unidentified non-A, non-B, non-C agent. PMID: 7524052

10. J Pediatr. 1994 Sep;125(3):463-5. Passive transfer of hepatitis antibodies during intravenous administration of immune globulin. Karna P, Murray DL, Valduss D, Mattarella N, Dyke JW, Maier GA. Department of Pediatrics and Human Development, Michigan State University, East Lansing. We studied the effect of intravenous immune globulin (IVIG) infusion on the levels of hepatitis B and C antibodies in 10 premature babies. All four tested lots of a commercially purchased IVIG preparation were found to contain substantial amounts of hepatitis B core and hepatitis C antibodies. Our results show that passive transfer of hepatitis B and C virus antibodies occurred after IVIG infusion, and that the levels were dependent on the quantity of IVIG given. When assessing neonates for hepatitis, the factor of receipt of blood products, including IVIG, needs to be considered to interpret laboratory results. PMID: 8071759

11. Anti-Hepatitis C Antibodies  Passive transfer of antibodies only ?  Seroconverson without hepatitis ?  Subclinical infection ?

12. Case 2  85 year old female  left breast lymphoma (extranodal marginal zone)  CAD, CHF, diabetes  upper GI bleed  Transfused  7 units 3-2  5 units 3-1 (+ 4 FFP)  2 units 2-26  No history of transfusion reaction  Newly dropping hematocrit  Type and Screen 3-29-10

13. Hemoglobin: 2-7-10 to 4-3-10 3-2-10 Last T 2-16-10 First T

14. Lab Workup  Type: B pos  Screen: 2+ and 3+  Panel: 1+ to 4+ in 8/11 cells  Auto-control: 2+  DAT: negative  Eluate: 3+ and 4+ to screen cells  Eluate Panel: >C & >E  Antisera to patient RBC:  C = mixed field  E = negative Mixed field = Some patient cells (C neg) + Some transfused cells (C pos) Mixed field = Some patient cells (C neg) + Some transfused cells (C pos)

15. Concise Rh System AntigenAllelic PartnerAntibodies D(none)Naturally occurring CcAcquired Ee

16. Delayed Transfusion Reactions  Production of antibodies against antigens on RBCs of transfused blood (or pregnancy)  May take days – months – years to form antibodies  1-1.6% of transfusions form antibodies  If transfused another unit with those antigens  May result in delayed hemolysis

17. Delayed Transfusion Reactions TypeSignsMechanismTimeline DHTR (Hemolytic) 1:2500 Ts Fever, anemia, leukocytosis, hemoglobinemia, hemosiduria,  LDH & bili Extravascular hemolysis Days to weeks DSTR (Serologic) 1:1250 Ts Unexplained anemia, no response to additional transfusions * NO laboratory evidence of hemolysis Presence of alloantibody NO lab hemolysis Days to weeks, Abs may become undetectable over months to years Red Cell ParasiteFeverIntravascular hemolysis Days to weeks GVHDFever, rash, GI symptomsNO hemolysisDays to weeks * DHTR/DSTR antigens: Kidd > Duffy > Kell > MNS * DAT can be negative if no/few transfused red cells remain

18. Hemoglobin: 2-7-10 to 4-3-10 3-2-10 Last T 2-16-10 First T Also:  LDH & bilirubin  Haptoglobin + Coombs DELAYED HEMOLYTIC TRANSFUSION REACTION

19. Acute Transfusion Reactions TypeSignsMechanismTreatment HemolyticFever, chills, hypotension ABO incompatibility, Intra- or Extra- vascular hemolysis Lasix, Morphine, Pressors Febrile Nonhemolytic Fever chillsCytokines in unit, Abs to donor WBCs Leukoreduce Antipyretics Allergic Hives, flushing  anaphylactic Abs to donor plasma proteins Antihistamine TRALIARDSDonor Abs to patient WBCs Supportive Defer donor TACOSOB, HTNVolume overloadLasix, Oxygen SepsisFever, chills, hypotension Bacteria in donor blood Antibiotics

20. Thank you