Platelet Refractoriness
Laura Cooling MD, MS
Associate Medical Director
Transfusion Medicine
Platelet Kinetics
circulating life span 8-10 days
Circulation
60%
Spleen
30-40%
10-12% loss/day
20% endothelial integrity
80% senescence
Definitions of Refractoriness
2-3 consecutive platelet transfusions by CCI
or PPR
REFRACTORINESS
ALLOIMMUNIZATION
Platelet Refractoriness
Poor response to platelet by immune or nonimmune factors
Immune (25-50%)
Alloimmunization
Autoantibodies
Passive Immunity
Drug-related
Nonimmune (50-75%)
Fever
Infection
Splenomegaly
Drugs/Antibiotics
Consumption
Bleeding
Platelet Dose
Effect of Platelet Count, Splenomegaly
and “Refractoriness” on Platelet Survival
75%
Normal
Plt>200K
65%
50%
Refractory
Normal
Plt<50K
Asplenia
Splenomegaly
Plt<50K
1 hr
20-24 hr
2 days
8-10 days
% Platelet Recovery (PPR)
Platelet Response and Kinetics in Normal
and Refractory Patients
PPR = 60-66%
Normal
PPR>30%
20-24 hrs
Immune
Hypersplenism
Nonimmune
24 hrs
Evaluating Platelet Transfusion Response
Corrected Count Increment (CCI):
• In vivo Measurement Platelet Survival
• Number of Platelets Transfused
• Size of Patient
• Requires a 1-4 hour post-platelet count
• Positive Predictor platelet survival at 20 hrs
Corrected Count Increment
Whole Blood Derived Platelet Concentrates
CCI= (post-platelet count - pre-platelet count)(BSA)
(3.5 [approximate # platelets transfused x 1011])
CCI > 7.5 Good Response
* Platelet count at 1 hour post transfusion,
BSA=body surface area in M 2
Example: Patient (1.7 M 2) transfused with 5 units
pooled platelets for platelet count=2. At 1 hr,
plts=30K. CCI=(30-2)(1.7)/3.5=13.6
Specialty Products
Documented Refractory Patients
Pathology consultation and approval
• Crossmatched Platelets (First Choice)
– Single donor apheresis platelets “crossmatched”
solid-phase technique with patient’s serum
• HLA Platelets
– require HLA antibody screen + HLA type
– Antigen negative: lack specific HLA antigens
– HLA-matched: A or B matches only, require 810 days from Los Angeles Red Cross
Influence of Patient Factors and Storage Time
on Platelet Transfusion Response*
*Slichter 1997, adapted from Norol 1994
50
45
40
35
30
25
20
15
10
5
0
NS
<8 hrs
< 48 hrs
p<0.05
p<0.05
p<0.05
Stable
Amphotericin
89%
65%
GVHD
51%
Sepsis
21%
VOD
13%
Comparison of Mean PPR with Random, HLA
(Antigen Negative and Matched), or Crossmatched
Platelets
Petz et al. Transfusion 2000;40:1446-1456
35
Mean PPR
30
25
Random
HLA-Ag Negative
HLA Matched
Crossmatch
20
15
10
5
0
PRA 0
PRA 1-10
PRA 10-80
PRA 80-100
% HLA Typed Donors (n=7247)
Percent of HLA-Matched (A+BU) vs HLAAntigen Negative Compatible Platelet Donors
per Patient
40
35
30
Petz et al. Transfusion 2000;40:1446-1456
33.8
A+BU HLA
28.8
Ag Neg HLA
25
18.6
20
15
9.5
10
5
0
0.7
PRA 1-19
0.6
20-39
0.6
40-59
0.1
60-85
2.1
0.3
>85
Corrected Count Increment
CCI: Apheresis Platelet Concentrates
=(Post-platelet count - Pre-platelet count)(BSA)*
# platelets transfused (x1011)
CCI >7500 (1 hr) or >5000 (20 hr)
* Body surface area (M2)
Ex. A woman transfused with SDP (4 x 1011).
Platelet count pre=8, post=42. BSA=1.5 M2
CCI=(42-8)(1.5)/4=12.7
Percentage Platelet Recovery (PPR)
Percent Predicted Count (PPC)
=No. platelets transfused x 0.67 x .001
blood volume (mL)
Percent Platelet Recovery (PPR)
= (post-platelet - pre-platelet count)x 100%
percent predicted count
Normal = PPR 60% (1 hr) or > 30% (20 hr)
Refractoriness = PPR < 30% (1 hr) or < 20% (20 hr)