Nick Bandarenko, MD Duke University Transfusion Service
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1 Nick Bandarenko, MD Duke University Transfusion Service
2 AN UNEXPECTED ADVERSE EVENT
3 Case #1 3 month old 4.3kg boy with congenital heart malformation Ventricular Septal Defect (VSD) Failure to thrive and Congestive Heart Failure Presented for surgical VSD closure CPB circuit: Standard neonatal prime: 1 unit PRBCs (AS 3 4 days old, LR), 1 unit FFP NaHCO3, heparin, solumedrol, CalGlu
4 Case #1 RBC Special Needs for Neonatal (<4 month old) Cardiac Surgery Leukocyte reduced CPDA <10 days or if not available AS 3 then AS 1 (<14 days) Irradiated
5 Case #1 Baseline Labs ABG unremarkable Co-ox: Hb 9.7 g/dl, COHb 3.3%, lactate 1.4 mmol/l Sternotomy, pericardium dissected, aortic then SVC cannulation Uneventful CPB initiation, IVC cannulation rso 2 remained around baseline Activated Clotting Time (ACT) at 7 mins
6 Case #1 Pulse-oximeter: indirectly monitors the oxygen saturation of a patient's blood (as opposed to measuring oxygen saturation directly through a blood sample) by the oxy/deoxyhemoglobin ratio calculated from the ratio of the absorption of the red and infrared light during arterial contraction Limitation: Not a complete measure of respiratory sufficiency. A patient suffering from hypoventilation (poor gas exchange in the lungs) given 100% oxygen can have excellent blood oxygen levels while still suffering from respiratory acidosis due to excessive carbon dioxide. CO-oximeter measures absorption at additional wavelengths to distinguish CO from O 2 and determines the blood oxygen saturation more reliably
7 Case #1 CDI % SaO 2 Ignored COHb initially Cerebral Oxygenation began declining for no obvious reason 2 nd ABG confirmed COHb (11%) 100% O 2, Hb already high, flow ~ mls/kg/min, 32C
8 Case #1 Cerebral Oxygenation (Somanetics) continued to decline Ordered a new lead (wire) to monitor in case defective Considered possible sources of as source of COHb Checked head for signs of cerebral congestion Checked venous saturation (75%) Turned off forane gas as possible source Examined donor blood (very red unit of RBCs)
9 Case #1 Confirmed donor blood as source of COHb (COHb 15%!!) Called Transfusion Service Began searching literature
10 Case #1 COHb remained high during CPB VSD closed with dacron patch Performed partial exchange transfusion with a different unit of prbcs (cell saver washed) Removed 400mls and transfused 250mls
11 Case #1 Somanetics reading improved (sensor changed around this time)
12 Case #1 COHb 7.1% after partial exchange transfusion Weaned uneventfully XCL: 74 mins CPB: 135 mins Transferred to PCICU
13 Case #1 Lactate 1.4 mmol/l pre-cpb, up to 2.6 just prior to exchange tx, 1.9 immediately after exchange SVO 2 maintained ~75-80% throughout CPB run Normal SVO2 is 75%, which indicates that under normal conditions, tissues extract 25% of the oxygen delivered MAPs ~45mmHg COHb continued to decline to normal Discharged POD4
14 Lactate mmol/l / COHb % RSO2 Perfusion Parameters COHgB Lactate INVOS :38 8:44 CPB exch tx 9:33 10:18 10:46 11:02 Off cpb Time 12:10 13:20 17:30 23:
15 Carbon Monoxide (CO) Colorless, odorless, highly toxic gas Vehicle exhaust, fuel burning appliances, engine powered equipment, tobacco smoke, fire smoke, methane breakdown Leading cause of fatal poisoning in industrialized world Symptoms of poisoning resemble the flu CNS and myocardium most at risk w/ poisoning Produced naturally in the body from the breakdown of heme Multiple roles (memory, inflammation, liver, kidneys, heart) Chronic / Prolonged exposure can cause polycythemia
16 Carboxyhemoglobin (COHb) CO binds with Hb in blood to form carboxyhemoglobin (COHb) Hb affinity for CO is 240 times greater than for O 2 Decreases O 2 carrying capacity of blood and shifts OHDC to the left, leading to tissue hypoxia Fetal Hb takes up CO more readily - infants are more vulnerable to its effects Elimination: dissolved O 2 is eventually able to displace CO from Hb Half-life: 4-6 hrs on room air, 74+/-25 mins with 100% O 2
17 OHDC
18 Carboxyhemoglobinemia Elevated levels of COHb in blood known as carboxyhemoglobinemia Normal levels/high levels and effects 0-2.5% non-smokers, 0-10% smokers Overt symptoms ~20%, subtle symptoms at lower levels Serious toxicity ~ 25%, fatal ~70% Treatment: 100% O 2
19 Literature Review Blood bank studies in 80s recommended levels be reported on units Carboxyhemoglobin levels decreased as storage time increased (Uchida, 1990) Anecdotal case reports
20 9.4 kg VSD, primed w/ 150 mls PRBC COHb level of 3.7%, donor unit 7.2%, 100%O 2, remained high until following morning
21 468 units, avg COHb 0.78%, 48 units >1.5%, highest 12% Only units with levels <1.5% used for pediatric cardiac surgery
22
23 Discussion Donor: Increased Hb on first patient ABG and in donor unit may indicate prolonged CO exposure Smoker? CO leak at home or vehicle? Likes to grill in the garage?
24 Discussion The Transfusion Service contacted the Blood Donor Center Investigation of the blood donor revealed that he drove an old truck with a bad muffler The level of COHb in the donated unit suggested exposure to significant levels of CO. Prolonged CO exposure may cause polycythemia, hence the donor would likely have normal or high Hgb on pre-donation screening
25
26 Summary Can get COHb from donor blood Monitoring can be tricky/misleading CO Ox better than pulse Ox Visual Inspection of Unit- Implicated unit was noted to be bright red Consider intro-operative measurement of prbcs for COHb Specifically for neonatal cardiac surgery patients who are at greatest risk Report Discoveries that may implicate donor health to Blood Center! v
27
28 What is the name of our galaxy?
29 Visual Inspection of RBC units Is required to be performed when dispensing blood Cannot detect bacterial contamination Does not involve comparing integral segments to the tubing in continuity to the unit Can be bypassed on rare units of blood Is required by regulations but does not directly benefit patients
30
31 Obstetrical Disaster Averted
32 Case #2 KL is a 38 year old female with an past obstetrical history significant for 3 prior spontaneous abortions at 6, 10, and 12 weeks followed by a twin gestation with IUFD at 24 weeks of one twin and post partum death of the second twin shortly after term delivery Cause of fetal/neonatal death intracranial hemorrhage associated with thrombocytopenia
33 Most likely diagnosis is Inherited clotting disorder Hemolytic disease of newborn Bad luck Congenital malformation Neonatal alloimmune thrombocytopenia
34 Neonatal Alloimmune Thrombocytopenia (NAIT) Syndrome of immune destruction of platelets by maternal antibody In this case, anti-hpa-1 Analogous to HDFN which involves destruction of fetal red cells by maternal antibodies to RBC antigen Mother becomes sensitized during pregnancy to fetal platelet specific antigen inherited from father IgG specific for the platelet antigen is formed and crosses the placenta Most common cause of severe fetal/neonatal thrombocytopenia Affected infants at risk for major bleeding- ICP
35 Case #2- Previous Testing Patient- HPA-1 negative Father- HPA-1 positive (homozygous) HPA-1 is a common platelet antigen To date 23 platelet specific antigens have been described Associated with DNA polymorphisms Localized to glycoproteins on platelet surface HPA-1 (HPA-1a) is associated with GPIIIa Most frequent antigen implicated in NAIT is Pl A1 80% of cases Antigen prevalence 98%
36 NAIT Platelet antigen Percent of cases of NAIT HPA-1a 80% HPA-5b 10% HPA-1b 4% HPA-3a 2% Other 6%
37 NAIT Incidence of ICH 10-30% Half occur in utero Risk of ICH inversely proportional to platelet count Highest when plt < 100,000/uL Occasionally may have associated hydrops due to extramedullary hematopoeisis anemia without red cell incompatibility Once delivered follow platelet count which gradually increases as maternal antibody disappears over 2-3 weeks
38 Case #2 Treatment for NAIT ANTENATAL Intravenous gammaglobulin 1g/kg/week Steroids Goals- ameliorate fetal thrombocytopenia Prevent intracranial hemorrhage Cordocentesis (1-2 % mortality) Clinician must balance risk of the procedure with risk of ICH Monitoring of platelet count IUT of platelets Antigen negative CMV reduced risk Irradiated Blood supplier may have HPA-1 negative donors
39 Case #2 Patient presented to Duke at 33 weeks with premature Rupture of Membranes receiving weekly IVIG and steroids Resulted in prolonged hospitalization with planned c-section 1 month away Ultrasound normal No cordocentesis for monitoring fetal platelet count What arrangements did the Transfusion Service make with clinical team and the Blood Center?
40 Case #2 Transfusion of antigen negative platelets may be life-saving Clinical Service- To NOTIFY Transfusion Service of impending delivery Assess if more than 1 unit of platelet may be required for management of fetus Plan on immediate IV access if any signs of bleeding and to begin transfusion of plts (before plt count result) Transfusion Service- To MAINTAIN one HPA-1 negative platelet inventory at all times Leukoreduced for CMV reduced risk Irradiated to prevent GVHD Volume Reduce platelet when notified of impending delivery Rh + OK
41 Case #2 Blood Center- Coordinated HPA-1 negative donations Provided in date HPA-1 negative platelet product every 4-5 days
42 Case #2 Clinical Course of newborn platelet counts Delivery A 68 B 84 C 85 D 114 Day Day Day Day Day No anemia, no signs of bleeding bruising or petechiae No transfusion of platelets required! v
43 Up to 80% of NAIT cases are associated with which maternal antibody? Anti-HPA-3a Anti-HPA-1b Anti-HPA-1a Anti-HPA-5b Anti-HPA-4a
44 Transfusion Associated Fever
45 Case #3 LG is a 74 year old female who has been receiving chemotherapy for leukemia. The patient has been unresponsive to therapy and is transfusion dependent. She presents to clinic with a platelet count of 9 X 10 9 /L and her WBC count is 11 x 10 9 /L. Pre transfusion her vital signs are temperature C, BP - 156/70 mm Hg, and a pulse of 104. She is premedicated with benadryl and tylenol. The platelets are infused over 30 minutes Post transfusion vital signs are 37.8 C, BP 152/70 mmhg, P= 88, R= 20 There were no signs or symptoms of an adverse transfusion reaction. Thirty minutes following her transfusion, she complains of feeling cold, followed by rigors. Her temperature is 37.5 C.
46 Case #3 The patient is kept in the clinic, and at 4 hours and 40 minutes she shows signs of respiratory compromise. At 5 hours her platelet count is 47 X 10 9 /L and her WBC count is 6.6 X Her temperature is 39.5 C, blood cultures are drawn, broad spectrum antibiotics started At 6 hours following the completion of her transfusion, the patient becomes apneic while on the elevator going to the ICU, suffers a cardiopulmonary arrest and is pronounced dead. Blood cultures from the patient and the platelet bag both grew Staph. warneri.
47 Case #3 What type of transfusion reaction did she experience? Given the high fever, and the drop in WBC count, one should have suspected a septic transfusion reaction. The cultures confirmed this suspicion. How common is this type of reaction? The risk of symptomatic bacterial contamination is thought to be 1/2000
48 What additional step is critical when bacterial contamination is suspected? Quarantine other products from donation Investigate donor for risks Protect other transfusion recipients from potentially contaminated product Also, Notify FDA verbally within 24 hours and in writing within 7 days
49 A Classic Case
50 Case #4 49 year old female Receives a single unit of FFP prior to elective surgery No prior transfusion history 45 minutes into the infusion she develops Chills Fever (102 deg C) Shortness of breath
51 Case #4 Progressive respiratory deterioration and BP Required mechanical ventilation, O2 Support 96 hours later Clinical improvement apparent Pulmonary infiltrates on chest xray still noted 7 days later This represents a fairly classic transfusion reaction known as
52 TRALI Transfusion Related Acute Lung Injury Acute onset Hypoxemia FiO2 < 300 or SPO2 < 90% on RA or other clinical evidence of hypoxemia Bilateral infiltrates on CXR No evidence of circulatory overload No preexisting ALI before transfusion During or within 6 hrs of transfusion No temporal relationship to an alternative risk factor
53 Case #4 Transfusion Associated Lung Injury Outcome in this case: Donor Center followed up and determined implicated donor had HLA Classs I antibodies to HLA-A2, A23, A24 Negative for platelet neutrophil /granulocyte antibodies Donor was a 54 y.o., 290 donations with NO prior adverse reaction reported 3 pregnancies over 30 ago Patient was negative for all antibodies
54 Volume 50, August 2010 TRANSFUSION
55 CONTACT DONOR CENTER TO START A TRALI INVESTIGATION AMERICAN RED CROSS Contact the Donor and Client Services Center (DCSC) to report complications of a potential TRALI related event Patient care questions should be directed to the Medical Director at Carolinas Region. The Donor and Client Service Center can be notified at The fax number to the DCSC is
56 To begin a TRALI investigation: Possible Recipient Complication Transfusion Reaction Report completed by the reporting hospital received by the DCSC case investigator submitted to the regional MD for evaluation. REPORT ALL PRODUCTS involved to ensure holds are placed on all involved donor records. MUST BE DONE to prevent subsequent donations, quarantine products
57 TRALI work up - Samples to send ARC from recipient* 1. HLA/HNA antibody testing 2 red tops 2. HLA/HNA antigen typing 2 EDTA tubes 3. HLA antigen and HLA antibody testing 2 red tops and 2 EDTA tubes 4. TOTAL: 4 red tops, 4 EDTA *consult with Blood Supplier for specific sample requirements v
58 The most common cause of transfusionassociated mortality reported to the FDA is Intravascular Transfusion Rxn with ABO incompatibility Post Transfusion Purpura TA-GVHD TRALI Transfusion acquired infection
59 Incidence and Mortality of Noninfectious Complications of Transfusion COMPLICATION INCIDENCE MORTALITY (%) Intravascular hemolysis with ABO Incompatibility 1:33,000 5 TA-GVHD 1:400, TRALI 1: PTP 1:200,
60 Multi alloantibodies in an immunocompromised patient
61 Case #5 35 month old female with Di George Syndrome s/p thymus transplant being evaluated for BMT transplant Multiple transfusion for anemia associated with red cell aplasia Presents with Hgb of 7.6 g/dl (baseline 10.6 to 11.5) Shortness of breath and cough lung nodules +Antibody Screen h/o anti- C, Jka, e, and warm auto
62 Selection of RBC units Need help from ARC <1% of donor population compatible with this combination of antibodies Responsiveness of ARC with frozen units from local distribution center Familiarity with the patient from prior transfusion episodes Maintaining local frozen inventory in case needed by Duke or adjacent hospital for this patient
63 Selection of Units SCIDS Severe Combined Immunodeficiency Syndrome (SCIDS) a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes Immuno-incompetent At risk for GVHD CMV other infections SPECIAL BLOOD NEEDS IRRADIATED, CMV Negative or CMV reduced risk (LR) v
64 The rationale for deglycerolizing frozen RBC s with extensive washing is that Glycerol. Is not approved by the FDA Is toxic to the kidneys Can cause anaphylaxis Can cause hemolysis Can cause thrombocytopenia
65 How many planets in the solar system have rings? Jupiter, Saturn, Uranus, and Neptune all have rings.
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