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Absolute Immature Platelet Fraction (IPF#)
The absolute-IPF (IPF#), calculated as IPF% x PLT count, reflects the number of immature
platelets in circulation and is a measurement of real-time thrombopoiesis. IPF# has been Causes of
used in clinical trials to assess the treatment effect of thrombopoietin receptor agonists, Thrombocytopenia
such as eltrombopag, and in platelet disorders of production and destruction, more
specifically in Immune Thrombocytopenia (ITP).6,7 • M
yeloablative therapy for
hematologic malignancies
In studies assessing the effect of platelet transfusion on IPF% and IPF#, platelet • ITP/TTP
transfusions were found to decrease the IPF% due to the increased circulating platelet
• Hepatitis C
count but did not affect the IPF# result, thus “validating the assay as a reflection of
ongoing platelet production by the marrow…”8 • Bone marrow transplant
• Acute myelogenous leukemia
IPF in the Clinical Setting
• PNH/aplastic anemia
Normal Ranges
• DIC
There is remarkably good correlation of reference ranges for IPF% between laboratories
• Splenomegaly
(Figure 1). A 2006 study9 reported a reference range of 0% to 6% (+/- 2SD) with the mean
value of 3.1%. The reproducibility of the assay was good, with coefficients of variation • Autoimmune Disease
(CV) ranging from 4.9% to 22.1%. As expected, the lower the IPF%, the higher the CV. • Bacteremia
IPF Normal Ranges by Source • HIT
3
95% Confidence
Subject No. of Cases Mean SD Range Level P*
Healthy 80 3.1 1.6 1.0 - 7.0 2.8 - 3.5 —
Destruction
ATP 37 15.0 7.1 3.6 - 35.4 12.7 - 17.2 <.0001
DIC 25 9.5 5.2 2.3 - 18.6 7.5 - 11.5 <.0001
All destruction 62 12.8 2.3 - 35.4 11.0 - 14.5 <.0001
Recovery
Chemotherapy 79 4.1 2.0 1.2 - 10.9 3.6 - 4.5 .001
BMT 8 8.0 4.2 4.3 - 15.3 5.1 - 10.8 <.0001
All recovery 87 4.4 2.5 1.2 - 15.3 3.9 - 4.9 <.0001
Suppression
AA/PNH 3 6.1 2.5 3.9 - 8.8 3.2 - 8.9 .019
Cancer 16 3.8 2.0 0.8 - 7.1 2.8 - 4.7 NS
All auppression 19 4.1 2.2 0.8 - 8.8 3.1 - 5.1 .05
Figure 2: IPF% in Different Populations of Thrombocytopenic Patients.9
IPF in Hepatitis C/Liver Disease Although it is customary to follow engraftment following allogenic stem cell
neutrophil recovery after hematologic transplantation, finding that IPF preceded
Additional examples of clinical utility of
transplantation procedures, IPF may be engraftment.
IPF% is evaluation of the mechanism of
a more reliable parameter since it is not
thrombocytopenia in Chronic Hepatitis Other uses for IPF have been described.
affected by graft-versus-host disease.
C patients as recently described by Briggs et al.3 have suggested that the
Zucker and colleagues12 followed IPF%
Zucker et al.11 The authors concluded IPF parameter may be able to alleviate
in 50 patients undergoing peripheral
that this mechanism is similar to the need for bone marrow examinations
hematopoietic cell transplants and
thrombocytopenia associated with liver as well as to determine if platelet
found that IPF recovered on average 3.1
disease. transfusions are necessary.
days prior to platelet count recovery
IPF% was monitored in all patients (Figure 3). Takami et al.14 also reported
and found to be normal or increased, the use of IPF as a predictor of platelet
supporting the idea that peripheral
destruction and sequestration are the 14
major causes of the thrombocytopenia in 13.2
12 12.5
Hepatitis C and liver disease in general.
10
Mean Days
4
IPF in Acute Myeloid Leukemia groups of patients may be accounted What’s Out?
and Myelodysplasia (AML/ for by the production of younger,
1. Inaccurate PLT measurements at the
MDS) Versus Immune larger platelets in ITP patients versus
very low levels, as can be seen in
Thrombocytopenia (ITP) AML/MDS patients who had lower IPF
severe thrombocytopenia.
values and smaller platelets (Figure 4).
It has been difficult to measure platelet
function in the presence of severe 2. Morphologic identification of large/
IPF in the Assessment of
thrombocytopenia, a finding in both young platelets.
Thrombopoietin Agonists
AML/MDS and ITP patients. Psaila et 3. Waiting for Absolute Neutrophil
Another key role of IPF is in
al.15 have noted that “Platelet count Count recovery to determine bone
determining the efficacy of various
alone does not always predict bleeding marrow recovery.
treatment protocols for ITP, such as
in severely thrombocytopenic patients”,
thrombopoietin receptor agonists
i.e., it is necessary but not sufficient. What’s In?
(TPO-A). A study by Barsam et al.7
The study found that the difference in 1. A comprehensive platelet evaluation
showed that patients receiving TPO-A
bleeding tendencies between these two beginning with a fluorescent
have a higher IPF.
platelet count and simultaneous
Platelet parameters in ITP and AML/MDS measurement of the IPF to evaluate
A B the maturity of circulating platelets as
Platelet count Platelet size an indicator of rate of PLT production
Platelet count μL-1
50,000 250
(thrombopoiesis), i.e., using IPF
40,000 200 to assist the physician in defining
FLS
3 20 (IPC)
%
5
Conclusion
Immature Platelet Fraction is a parameter that, although new to the clinical setting, has been studied for over a decade. IPF can
function as a routine value reported with every platelet count in certain patient populations or as a reflex test based on your
laboratory’s platelet count cut-off. It provides guidance to the physician on the etiology of various thrombocytopenic states, and
may help anticipate bone marrow and platelet recovery. Regardless of how it is applied, you will be supporting the delivery of high
quality, cost effective patient care for a positive impact on patient outcomes.
Identify the clinical lab tests that currently trigger follow-up testing by physicians
3. What existing laboratory tests or clinical conditions trigger additional platelet studies in your institution?
4. What are the clinical conditions associated with thrombocytopenia at your organization?
5. What hospital service lines would need to know that a patient is thrombocytopenic?
8. How can the laboratory educate physicians and nurses, pharmacists, coding and other ancillary departments about
the value of the IPF parameter in the differential diagnosis of thrombocytopenia?
6
Bibliography
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Disclaimer Notice of Intended Use
The uses or clinical applications described in “The Immature Platelet Fraction (IPF)
these publications have not been approved parameter on the XN- and XE-Series Automated
or cleared by the FDA. It is the clinician’s Hematology Analyzers is intended for in vitro
responsibility to validate any off-label diagnostic use to enumerate the immature
applications for use in routine clinical practice. platelet fraction”.