Best Practice for Platelet and
Plasma Transfusion
Nicole Draper, MD
Platelets
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
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
Platelet Transfusion Indications
• Prophylaxis
– Non-bleeding patients
– Platelet count <10x109/L
• Treatment
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 (150400mg/dL)
Actively bleeding
– Bleeding/surgical patient
– Platelet count <50x109/L typically
– Neurological often <100x109/L
– Platelet dysfunction (aspirin, clopidogrel,
uremia, plastic, pumps, congenital)
Platelet Count and Bleeding
Often platelets will not stop
bleeding, but need to prevent
levels so low as to have
additional spontaneous
bleeding
Harker LA, Slichter SJ. N Engl J Med 1972;287:156
Slichter SJ. Transfus Med Rev. 2004 Jul;18(3):153-67
Platelet Count and Bleeding
http://imaging.ubmmedica.com/cancernetwork/journals/oncology/images/o0009sup8cf2.gif
Platlet Count and Procedures
McVay PA, Toy PT. Transfusion 1991;31(2):164-71.
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.
Platelet Dysfunction: Aspirin
Figure 3 . Before and after transfusion platelet
function assay results with change in platelet
function.
Figure 2 . Before and after transfusion platelet function
assay results without change in platelet function.
Joseph B, Pandit V, Sadoun M, Larkins CG, Kulvatunyou N, Tang A, et al. J Trauma
Acute Care Surg. 2013;75(6):990-4.
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)
Platelet Dysfunction: Uremia
TMRE
PS Exposure
Enhanced platelet apoptosis in chronic uremic patients.2014 Mar 24.
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.
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
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
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
Question 1
An Rh+ platelet is transfused to an Rhpatient. 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
Rh Compatibility
Recipient
RhRh+
•
•
•
RBC
Rh-
Plasma
Rh-, Rh+
Platelets
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
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.
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
Platelet Refractory
• Unresponsive to platelet transfusion
– Immune or nonimmune? 10-60 minute posttransfusion count
• Nonimmune causes
30
– Splenomegaly
25
– Fever
20
– Sepsis
15
– Bleeding
10
– DIC/Mechanical
5
– Drug
0
0
15
30
45 min
60
75
Immune
Nonimmune
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
Case 2
50-year-old woman with suspected aplastic
anemia
Pre Plt Count
2/21
2/22
2/22
1830
0030
1030
5
3
4
Post Plt Count
2030
0130
1400
3
4
4
Platelet Refractory: PRA
HLA-Matched Platelets
Apheresis Platelet Unit
Case 2
50-year-old woman with suspected
aplastic anemia
Pre Plt Count
2/21
2/22
2/22
2/28
3/1
3/2
1830
0030
1030
1230
1300
1800
5
3
4
3
27
22
Post Plt Count
2030
0130
1400
1330
3
4
4
50
2100
56
Plasma
Plasma
Volume:
200 – 600 mL
Content:
Plasma
Anticoagulant
200 mL
250 mL
300 mL
500 mL
600 mL
PLASMA
=
INR = 1.3
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
Handling Options for FFP
FFP
Stored frozen
< -18°C
FFP,
Thawed
Thawed at
30-37ºC
Store at
1-6ºC
>24 h
Transfuse
Thawed
Plasma
(up to 5 days after thawing)
Coagulation Factor Activity of
Thawed Plasma
Day 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
Tabular entries as % activity NS = not statistically significant
Downes K et al. Transfusion 2001;41:570
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
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
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
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
Plasma Dosage and Effect
Determinants
PLASMA
PLASMA
Rx: 2 units??
Patient size
Bleeding site
Factor activity: Initial, target
Factor concentration in plasma
Factor half-life in vivo
Unit volume
USUAL DOSE FOR CONTROL
OF BLEEDING: 10-20 mL/kg
70 kg x 15mL/kg x 1unit/250ml = 4.2
4 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
Abnormalities in Coagulation Testing
do not Necessarily Indicate a
Clinical Coagulopathy
Fibrinogen
Factor V
Factor VII
Factor VIII
Normal
200-400mg/dL
1 U/mL
1 U/mL
1 U/mL
Hemostatic
50-100mg/dL
5-25%
5-25%
5-25%
Normal concentration: 1 U/mL = 100% activity
Edmunds LH. Hemostasis and thrombosis: basic principles and clinical practice. 4th ed. 2001 p1031-43
Using Screening Tests to Predict
Plasma Need
Mild elevations of PT, INR, aPTT overestimate
clinical benefit of transfusing plasma for patients in
most clinical situations.
Generally recommended transfusion trigger points
in appropriate 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
Prophylactic Plasma Transfusion
Almost no effect with an INR <1.85
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.
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
Plasma Transfusion for Invasive
Procedures
Technical skill of the person performing the
procedure inversely correlates with bleeding
Segal JB, Dzik WH. Transfusion 2005;45:1413-25
http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2005.00546.x/full
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
TEG
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).
Poston R et al. Eur J Cardiothorac Surg 2005;27:584-591
TEG
Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting. Semin Thromb Hemost.
2005;31(4):426-40.
Effect of Body Temperature on
Coagulant Activity
70
Seconds
60
50
40
PTT
PT
30
20
10
0
37
34
31
oC
Rohrer MJ, Natale AM. Crit Care Med 1992;20:1402-5
28
Effect of Acid/Base Balance
on Coagulant Activity
Meng ZH et al. J Trauma 2003;55:886-91
© 2003 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc.
Question 3
56-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
At the Bedside
• Clerical check
• Visual check
• 170-260µ filter removes
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
fibrin
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
Possible Side Effects
• More likely with massive transfusion
– Hypothermia
– Hyperkalemia
– Metabolic acidosis (citric acid)
– Hypocalcemia, hypomagnesemia
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
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
– Allergic
– TA-GVHD
●
Thrombocytopenia
– Posttransfusion purpura
– Platelet refractory
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/gu
idancecomplianceregulatoryinformation/guida
nces/blood/ucm364565.htm
Questions