nick bandarenko , md duke university transfusion service
TRANSCRIPT
Nick Bandarenko , MD
Duke University Transfusion Service
AN UNEXPECTED ADVERSE EVENT
• 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
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
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
• rSO2 remained around baseline
• Activated Clotting Time (ACT) at 7 mins
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/deoxyhemoglobinratio 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 O2 and determines the blood oxygen saturation more reliably
Case #1
• CDI 500 100% SaO2
• Ignored COHb initially
• Cerebral Oxygenation began declining for no obvious reason
• 2nd ABG confirmed COHb (11%)
• 100% O2, Hb already high, flow ~150-175mls/kg/min, 32C
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)
Case #1
• Confirmed donor blood as source of COHb (COHb 15%!!)
• Called Transfusion Service
• Began searching literature
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
Case #1
• Somanetics reading improved (sensor changed
around this time)
Case #1
• COHb 7.1% after partial exchange transfusion
• Weaned uneventfully
• XCL: 74 mins
• CPB: 135 mins
• Transferred to PCICU
Case #1
• Lactate 1.4 mmol/L pre-CPB, up to 2.6 just prior to exchange tx, 1.9 immediately after exchange
• SVO2 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
Case #1
Perfusion Parameters
0
2
4
6
8
10
12
7:38
8:44
9:33
10:18
10:46
11:02
12:10
13:20
17:30
23:50
Time
Lacta
te m
mo
l/L
/
CO
Hb
%
010203040
50607080
RS
O2
COHgB
Lactate
INVOS
CPB
exch tx
Off cpb
• 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
Carbon Monoxide (CO)
CO binds with Hb in blood to form carboxyhemoglobin (COHb)
Hb affinity for CO is 240 times greater than for O2
Decreases O2 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 O2 is eventually able to displace CO from Hb
Half-life: 4-6 hrs on room air, 74+/-25 mins with 100% O2
Carboxyhemoglobin (COHb)
OHDC
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% O2
Carboxyhemoglobinemia
• Blood bank studies in 80s – recommended levels be reported on
units
• Carboxyhemoglobin levels decreased as storage time increased
(Uchida, 1990)
• Anecdotal case reports
Literature Review
COHb level of 3.7%, donor unit 7.2%, 100%O2, remained high
until following morning
9.4 kg VSD, primed w/ 150 mls PRBC
468 units, avg COHb 0.78%, 48 units >1.5%, highest 12%
Only units with levels <1.5% used for pediatric cardiac
surgery
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?
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
Discussion
• 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
Summary
What is the name of our galaxy?
Visual Inspection of RBC units
Is required by regulations but does not directly benefit patients
Can be bypassed on rare units of blood
Does not involve comparing integral segments to the tubing in continuity to the unit
Cannot detect bacterial contamination
Is required to be performed when dispensing blood
Obstetrical Disaster Averted
• 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
Case #2
Most likely diagnosis is
Inherited clotting disorder
Congenital malformation
Hemolytic disease of newborn
Bad luck
Neonatal alloimmune thrombocytopenia
• 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
Neonatal Alloimmune Thrombocytopenia
(NAIT)
• 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%
Case #2- Previous Testing
• Platelet antigen Percent of cases of NAIT
• HPA-1a 80%
• HPA-5b 10%
• HPA-1b 4%
• HPA-3a 2%
• Other 6%
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
NAIT
• 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
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?
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
Case #2
• Blood Center-
– Coordinated HPA-1 negative donations
– Provided in date HPA-1 negative platelet product every
4-5 days
Case #2
• Clinical Course of newborn platelet counts
• Delivery
• A 68
• B 84
• C 85
• D 114
• Day 1 136
• Day 2 147
• Day 3 166
• Day 4 272
• Day 5 412
• No anemia, no signs of bleeding bruising or petechiae
• No transfusion of platelets required !
• v
Case #2
Up to 80% of NAIT cases are associated with
which maternal antibody?
Anti-HPA-4a
Anti-HPA-5b
Anti-HPA-3a
Anti-HPA-1b
Anti-HPA-1a
Transfusion Associated Fever
• 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 109/L and her WBC count is 11 x 109/L.
• Pre transfusion her vital signs are temperature - 37.3 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.
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 109/L and her WBC count is 6.6 X 109.
• 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.
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
Case #3
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
A “Classic” Case
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
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…
• 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
TRALI – Transfusion Related Acute Lung Injury
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
Volume 50, August 2010 TRANSFUSION
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 1-866-236-3276
The fax number to the DCSC is 1-888-719-3535.
CONTACT DONOR CENTER TO
START 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
To begin a TRALI investigation:
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
The most common cause of transfusion-
associated mortality reported to the
FDA is
Transfusion acquired infection
Intravascular Transfusion Rxn with ABO incompatibility
TA-GVHD
Post Transfusion Purpura
TRALI
COMPLICATION INCIDENCE MORTALITY (%)
Intravascular
hemolysis with ABO
Incompatibility
1:33,000 5
TA-GVHD 1:400,000 90
TRALI 1:5000 5
PTP 1:200,000 0-13
Incidence and Mortality of Noninfectious
Complications of Transfusion
Multi alloantibodies in an immunocompromised patient
• 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
Case #5
• 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
Selection of RBC units
• 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
Selection of Units SCIDS
The rationale for deglycerolizing frozen
RBC’s with extensive washing is that
Glycerol….
Can cause thrombocytopenia
Is not approved by the FDA
Can cause anaphylaxis
Is toxic to the kidneys
Can cause hemolysis
How many planets in the solar system have
rings?
Jupiter, Saturn, Uranus, and Neptune all
have rings.