Platelet Refractoriness

Laura Cooling MD, MS

Associate Medical Director

Transfusion Medicine

Platelet Kineticscirculating life span 8-10 days

Spleen30-40%

Circulation60%

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

Immune (25-50%)

Alloimmunization

Autoantibodies

Passive Immunity

Drug-related

Nonimmune (50-75%)

Fever

Infection

Splenomegaly

Drugs/Antibiotics

Consumption

Bleeding

Platelet Dose

Poor response to platelet by immune or nonimmune factors

Asplenia

NormalPlt>200K

SplenomegalyPlt<50K

NormalPlt<50K

Refractory

1 hr 20-24 hr 2 days 8-10 days

Effect of Platelet Count, Splenomegaly and “Refractoriness” on Platelet Survival

50%

75%

65%

24 hrs

NormalPPR>30%20-24 hrs

PPR = 60-66%

NonimmuneImmuneHypersplenism

% P

late

let R

ecov

ery

(PP

R)

Platelet Response and Kinetics in Normal and Refractory Patients

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 ConcentratesCCI= (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 8-10

days from Los Angeles Red Cross

Influence of Patient Factors and Storage Time on Platelet Transfusion Response*

*Slichter 1997, adapted from Norol 1994

05

101520253035404550

Stable Amphotericin GVHD Sepsis VOD

<8 hrs< 48 hrs

89% 65% 51% 21% 13%

NS

p<0.05 p<0.05p<0.05

Comparison of Mean PPR with Random, HLA (Antigen Negative and Matched), or Crossmatched

PlateletsPetz et al. Transfusion 2000;40:1446-1456

0

5

10

15

20

25

30

35

PRA 0 PRA 1-10 PRA 10-80 PRA 80-100

RandomHLA-Ag NegativeHLA Matched Crossmatch

Mea

n P

PR

Percent of HLA-Matched (A+BU) vs HLA-Antigen Negative Compatible Platelet Donors

per Patient Petz et al. Transfusion 2000;40:1446-1456

0

5

10

15

20

25

30

35

40

PRA 1-19 20-39 40-59 60-85 >85

A+BU HLA

Ag Neg HLA

0.7 0.6 0.6 0.1 0.3

33.8

% H

LA

Typ

ed D

onor

s (n

=72

47)

28.8

18.6

9.5

2.1

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 countNormal = PPR 60% (1 hr) or > 30% (20 hr)

Refractoriness = PPR < 30% (1 hr) or < 20% (20 hr)