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Best Practice for Platelet and Plasma Transfusion
Nicole Draper, MD
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Platelets
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Platelet Storage and QC
• Whole-blood derived or apheresis
• 5 days at 20-24 oC– Temp needs to be maintained in transport,
while held in OR or ICU etc.
• Gently agitated
• Stored in plasma or additive solution
• Must test for bacterial contamination
• Must have >3.0 x 10 11 platelets per apheresis unit
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Case 1
• 30-year-old woman with h/o tetralogy of Fallot with cadaveric pulmonic valve, ASD closure device.
• Admitted with right heart failure found to have pulmonic valve vegetations complicated by severe pulmonic regurgitation.
• OR tomorrow for redo pulmonary valve replacement
• Cardiac bypass pump
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Platelet Transfusion Indications
• Prophylaxis– Non-bleeding patients– Platelet count <10x109/L
• Treatment– Bleeding/surgical patient– Platelet count <50x109/L typically– Neurological often <100x109/L– Platelet dysfunction (aspirin, clopidogrel,
uremia, plastic, pumps, congenital)
Hgb 6.8 (11-16g/dL)Plt 146 (150-400x109/L)ACT 353 (74-137sec)PT 23.8 (11.4-14.4 sec)Fibrinogen 129 (150-400mg/dL)Actively bleeding
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Platelet Count and Bleeding
Harker LA, Slichter SJ. N Engl J Med 1972;287:156 Slichter SJ. Transfus Med Rev. 2004 Jul;18(3):153-67
Often platelets will not stop bleeding, but need to prevent levels so low as to have additional spontaneous bleeding
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Platelet Count and Bleeding
http://imaging.ubmmedica.com/cancernetwork/journals/oncology/images/o0009sup8cf2.gif
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Platlet Count and Procedures
McVay PA, Toy PT. Transfusion 1991;31(2):164-71.
.
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Platelet Count and Procedures
• PTs and PTTs 1.1-1.5 times midrange normal levels and platelet counts 50-99 x 10(9)/L.
• Percutaneous liver biopsy 177 inpatient procedures (155 standard, 22 fine needle).
• Bleeding complications in patients with platelet counts greater than or equal to 50 x 10(9)/L was 3.4% (6 of 175), with no significant difference from patients with normal parameters.
• Highly associated with bleeding complications: a patient diagnosis of malignancy, 14% (7 of 50) compared with 0.8% (1 of 127) among other patients (P less than 0.001).
McVay PA, Toy PT. Am J Clin Pathol 1990;94(6):747-53.
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Platelet Dysfunction: Aspirin
Figure 2 . Before and after transfusion platelet function assay results without change in platelet function.
Figure 3 . Before and after transfusion platelet function assay results with change in platelet function.
No difference in the progression of ICH (37.5% vs. 30%, p = 0.7), neurosurgical intervention (12.5% vs. 15%, p = 0.8), and platelet count (240.9 vs. 252.1 p = 0.32)Joseph B, Pandit V, Sadoun M, Larkins CG, Kulvatunyou N, Tang A, et al. J Trauma
Acute Care Surg. 2013;75(6):990-4.
.
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Platelet Dysfunction: Uremia
TMRE
PS Exposure
Enhanced platelet apoptosis in chronic uremic patients.2014 Mar 24.
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Platelet Dysfunction: CPB• Several studies have found that laboratory
predictors of platelet dysfunction do not significantly correlate with bleeding after CPB.
• There is a clear correlation between the duration of CPB and the BMI with blood loss.
Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting. Semin Thromb Hemost. 2005;31(4):426-40.
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Platelet Transfusion Contraindications
• Nonbleeding patients on antiplatelet medications or with platelet dysfunction extrinsic to the platelet (uremia, von Willebrand disease)
• Activation or autoimmune destruction of endogenous platelets (HIT, TTP, ITP) unless there is life-threatening hemorrhage
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Blood Samples• Two unique patient identifiers
• Zero-tolerance for clerical errors– Most common cause of fatal hemolytic
transfusion reactions
• New sample every 3 days required if– Pregnant or transfused RBCs in the past 3 months– Usually a universally applied
criteria for RBCs
• Platelets and plasma often transfused on historical blood type
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Platelet Compatibility
• Weak ABO antigens on platelets
• 20-40% reduction in count increase if incompatible– Care more about the ABO antibodies in the plasma
that can hemolyze red cells– Soluble A or B antigenic substance in pt plasma
• Type-A donors recruited to apheresis platelets
• Type-O donors recruited to RBC donation
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Question 1
An Rh+ platelet is transfused to an Rh- patient. Which of the following does the patient need?
A. RhIg regardless of age and sex
B. RhIg if female with childbearing potential
C. No administration of RhIg
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Rh Compatibility
Recipient RBC Plasma Platelets
Rh- Rh- Rh-, Rh+ Rh-, (Rh+)
Rh+ Rh-, Rh+ Rh-, Rh+ Rh-, Rh+
• Anti-D not naturally occurring in plasma• No Rh(D)-antigen on platelets• Possible red cell contamination of platelets
– As little as 1 mL of blood in a liter of plasma is visually pink/red
– <0.001 mL RBC in an apheresis platelet unit– Tenths of a mL in pooled WB derived platelets
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RhIg and Platelets• Anti-D alloimmunization after
D-incompatible platelet transfusions: a 14-year single-institution retrospective review at Beth Israel Deaconess Medical Center.
• Of 130 eligible D− patients, 48% women and 57% immunocompetent, who received a total of 565 apheresis PLTs, none formed anti-D.
28%
Transfusion. 2014 Mar;54(3):650-4.
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Platelet Dosage and Effect
• Whole-blood-derived platelets and apheresis platelets have equivalent efficacy
• Dose– 1 apheresis platelet– 6-pack of whole blood platelets– 5-10 mL/kg in pediatric patients• Increase by 30-60 x 109/L in 70 kg adult• Typical life-span of 3-4 days post transfusion
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Platelet Refractory• Unresponsive to platelet transfusion
– Immune or nonimmune? 10-60 minute post-transfusion count
• Nonimmune causes– Splenomegaly– Fever– Sepsis– Bleeding– DIC/Mechanical– Drug
0
5
10
15
20
25
30
0 15 30 45 min 60 75
Immune
Nonimmune
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Platelet Refractory
• Platelet alloantibodies: Anti-HLA class I or platelet-specific antibodies– Previous transfusion or transplantation– Pregnancy– Recipient dependent, not dose
• Treatment: HLA-matched or crossmatched platelets
• Prevention: Leukocyte reduction
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Case 2
50-year-old woman with suspected aplastic anemia
Pre Plt Count Post Plt Count
2/21 1830 5 2030 3
2/22 0030 3 0130 4
2/22 1030 4 1400 4
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Platelet Refractory: PRA
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HLA-Matched Platelets
Apheresis Platelet Unit
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Case 250-year-old woman with suspected
aplastic anemiaPre Plt Count Post
Plt Count
2/21 1830 5 2030 3
2/22 0030 3 0130 4
2/22 1030 4 1400 4
2/28 1230 3 1330 50
3/1 1300 27
3/2 1800 22 2100 56
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Plasma
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Plasma
Volume: 200 – 600 mL
Content: PlasmaAnticoagulant
PLASMA250 mL
200 mL
300 mL
500 mL
600 mL
==INR = 1.3
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Plasma Types
• Fresh Frozen Plasma (FFP): frozen within 8 hours of collection
• Plasma Frozen within 24 Hours (PF24): frozen within 24 hours of collection
• Thawed Plasma (TP): derived from FFP or FP24 and maintained for a maximum of 5 days after the day of thaw
• Plasma Cryoprecipitate Reduced: low levels of fibrinogen, FVIII, vWF, FXIII, fibronectin
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Stored frozen < -18°C
FFP FFP,Thawed
>24 h
ThawedPlasma
(up to 5 days after thawing)
Handling Options for FFP
Thawed at30-37ºC
Store at1-6ºC
Transfuse
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Coagulation Factor Activity of Thawed
PlasmaDay 1 Day 2 Day 3 Day 4 Day 5 % change
Day 1 to 5 p
Fibr 225 224 224 224 225 0 NS
II 81 81 81 80 80 1 NS
V 79 75 71 68 66 16 NS
VII 90 81 76 72 72 20 NS
VIII 107 76 66 65 65 41 <.02
X 85 84 84 82 80 6 NS
Downes K et al. Transfusion 2001;41:570
Tabular entries as % activity NS = not statistically significant
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Question 2
All of the following are preferred uses of fresh frozen plasma except?
A. Massive transfusion
B. Reversal of warfarin anticoagulation
C. Treatment of hemophilia A
D. Treatment of TTP
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Plasma Transfusion Indications
• Bleeding or preoperative patients– Deficiency of multiple coagulation factors
• liver disease• warfarin therapy• massive transfusion • disseminated intravascular coagulation
– Specific factor deficiency, no concentrate
• Thrombotic thrombocytopenic purpura
• Rare specific plasma protein deficiency
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Contraindications
• When a coagulopathy can be corrected more effectively with a specific therapy– Vitamin K– Cryoprecipitated AHF– Prothrombin complex concentrates
• When blood volume can be safely and adequately replaced with other volume expanders
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Plasma Dosage and Effect
• The volume transfused depends on the clinical situation and patient size
• May be guided by laboratory assays of coagulation function
• No QC for plasma products
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PLASMAPLASMA
USUAL DOSE FOR CONTROLOF BLEEDING: 10-20 mL/kg
Plasma Dosage and Effect
DeterminantsPatient sizeBleeding siteFactor activity: Initial, targetFactor concentration in plasma Factor half-life in vivoUnit volumeRx: 2 units??
Hgb 6.8 (11-16)Plt 146 (150-400L)ACT 353 (74-137)PT 23.8 (11.4-14.4)Fibrinogen 129 (150-400)Actively bleeding
70 kg x 15mL/kg x 1unit/250ml = 4.2 4 units
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Edmunds LH. Hemostasis and thrombosis: basic principles and clinical practice. 4th ed. 2001 p1031-43
Abnormalities in Coagulation Testing
do not Necessarily Indicate a Clinical Coagulopathy
Normal HemostaticFibrinogen 200-400mg/dL 50-100mg/dLFactor V 1 U/mL 5-25%Factor VII 1 U/mL 5-25%Factor VIII 1 U/mL 5-25%
Normal concentration: 1 U/mL = 100% activity
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Mild elevations of PT, INR, aPTT overestimate clinical benefit of
transfusing plasma for patients in most clinical situations.
1.3 x upper limit of reference range (in seconds) - or –
1.5 x midpoint of reference range (in seconds))-McVay PA et al. AJCP 1990;94:737-53.-McVay PA et al. Transfusion 1991;31:164-71.-Counts RB et al. Ann Surg 1979; 190:91-9.-Ciavarella D et al. Br J Haematol 1987;67:365-8.-Auble T et al. Acad Emerg Med 2002;567-574-Stanworth SJ, Hematology Am Soc Hematol Educ Program 2007:179-86
Generally recommended transfusion trigger points in appropriate situations:
Using Screening Tests to Predict Plasma Need
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Prophylactic Plasma Transfusion
Almost no effect with an INR <1.85
Holland LL, Brooks JP Am J Clin Pathol. 2006 Jul;126(1):133-9. Abdel-Wahab OI, Healy B, Dzik WH Transfusion. 2006 Aug;46(8):1279-85
Patients receiving FFP and having pretransfusion and posttransfusion PT/INR. Patients with acute trauma, in the operating room, with excessive factor consumption (ie, DIC), or given PCC were excluded.
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Plasma Transfusion for Invasive Procedures
Segal JB, Dzik WH. Transfusion 2005;45:1413-25 http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2005.00546.x/full
Technical skill of the person performing the procedure inversely correlates with bleeding
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Thrombelastography (TEG)
• In 76 patients, routine coagulation tests (i.e. prothrombin time, fibrinogen level, d-dimer, and platelet count), thrombelastography, and whole blood aggregometry were obtained perioperatively and on days 1 and 3 after OPCAB.
• Intra- and postoperative blood loss was determined
Poston R et al. Eur J Cardiothorac Surg 2005;27:584-591
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Poston R et al. Eur J Cardiothorac Surg 2005;27:584-591
Significant correlation with 24h hemoglobin loss was seen only with a perioperative decline in the maximum amplitude of the TEG trace (R=0.45,
P 0.05) and fibrinogen levels (≪ R=0.43, P 0.05).≪
TEG
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TEG
Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting. Semin Thromb Hemost. 2005;31(4):426-40.
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Effect of Body Temperature on Coagulant Activity
0
10
20
30
40
50
60
70
37 34 31 28
PTT
PT
oC
Sec
on
ds
Rohrer MJ, Natale AM. Crit Care Med 1992;20:1402-5
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© 2003 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc.
Meng ZH et al. J Trauma 2003;55:886-91
Effect of Acid/Base Balance on Coagulant Activity
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Question 356-year-old woman with ESLD secondary to hepatitis C is reported to have sudden onset respiratory distress at approximately 10:30am. Intubated at 11am. She was scheduled for a procedure in IR and received 6 units FFP from 5am to 10am.
Time Hb INR T Bili Haptoglobin
0400 8.6 2.5 3.7
1130 6.9 1.9 4.1 17.0 (41–165)
A. Hemolysis
B. Fluid overload
C. TRALI
D. Bacterial contamination
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At the Bedside• Clerical check• Visual check• 170-260µ filter removes fibrin
clots, aggregates• 22-14 gauge needle/catheter
– 24 for pediatric if necessary
• 0.9% (normal) saline• Appropriate blood warmers• Transfusion must be completed within 4 hrs• Stop transfusion if suspect reaction
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Blood is a Drug
• The blood bank is the only part of the laboratory that is regulated by the FDA
– Blood products are biologic drugs
– Lab + pharmacy
• Include transfusion history as part of a drug history
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Possible Side Effects
• More likely with massive transfusion– Hypothermia
– Hyperkalemia
– Metabolic acidosis (citric acid)
– Hypocalcemia, hypomagnesemia
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Infectious Disease Transmission
• Infectious Disease Testing– HIV: anti-HIV-1/2, HIV RNA (1:1.5 million)– HCV: anti-HCV, HCV RNA (1:1.2 million)– HBV: HBsAg, anti-HBc, (1:280,000)– HTLV: anti-HTLV-I/II– WNV: WNV RNA– Syphilis: anti-Treponema pallidum– Chagas: based on history– CMV: optional
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Types of Transfusion Reactions• Fever
– Febrile– Hemolytic (delayed vs. acute)– Bacterial sepsis
• Respiratory distress– Transfusion related acute lung injury (TRALI)– Transfusion associated circulatory overload (TACO)– Allergic (anaphylaxis)
• Rash ● Thrombocytopenia– Allergic – Posttransfusion purpura– TA-GVHD – Platelet refractory
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References
• Transfusion therapy: clinical principles and practice / editor, Paul D Mintz. 3rd ed. AABB 2011.
• Technical manual / editor John D. Roback. 17th ed. AABB 2011.
• Circular of information for the use of human blood and blood components. http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/blood/ucm364565.htm
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Questions