Received: 20 July 2017 Revised: 9 August 2017 Accepted: 10 August 2017

DOI: 10.1002/pbc.26812

Pediatric
RESEARCH ARTICLE Blood &
The American Society of
Cancer Pediatric Hematology/Oncology

Utility of the immature platelet fraction in pediatric immune

thrombocytopenia: Differentiating from bone marrow failure
and predicting bleeding risk

Alicia McDonnell1 Karen L. Bride2 Derick Lim3 Michele Paessler2,3

Char M. Witmer1,2 Michele P. Lambert1,2

1 Department of Pediatrics, Perelman School

of Medicine at the University of Pennsylvania, Abstract

Philadelphia, Pennsylvania Background: Differentiating childhood immune thrombocytopenia (ITP) from other cause of
2 Division of Hematology, The Children's Hospital
thrombocytopenia remains a diagnosis of exclusion. Additionally factors that predict bleeding risk
of Philadelphia, Philadelphia, Pennsylvania for those patients with ITP are currently not well understood. Previous small studies have sug-
3 Department of Pathology and Laboratory
gested that immature platelet fraction (IPF) may differentiate ITP from other causes of thrombo-
Medicine, The Children's Hospital of Philadel-
phia, Philadelphia, Pennsylvania
cytopenia and in combination with other factors may predict bleeding risk.

Correspondence
Michele P. Lambert, Division of Hematology, The
Children's Hospital of Philadelphia, 3615 Civic
Center Blvd, ARC 316G, Philadelphia, PA 19104.
Email: lambertm@email.chop.edu
Methods: We performed a retrospective chart review of thrombocytopenic patients with an IPF
measured between November 1, 2013 and July 1, 2015. Patients were between 2 months and
21 years of age with a platelet count <50 × 109 /l. Each patient chart was reviewed for final diag-
nosis and bleeding symptoms. A bleeding severity score was retrospectively assigned.

Results: Two hundred seventy two patients met inclusion criteria, 97 with ITP, 11 with bone
marrow failure (BMF), 126 with malignancy, and 38 with other causes of thrombocytopenia.
An IPF > 5.2% differentiated ITP from BMF with 93% sensitivity and 91% specificity. Abso-
lute immature platelet number (AIPN) was significantly lower in ITP patients with severe to
life-threatening hemorrhage than those without, despite similar platelet counts. On multivariate
analysis, an IPF < 10.4% was confirmed as an independent predictor of bleeding risk at platelet
counts <10 × 109 /l in patients with ITP.

Conclusions: IPF measurement alone has utility in both the diagnosis of ITP and identifying
patients at increased risk of hemorrhage. Further study is required to understand the pathophys-
iological differences of ITP patients with lower IPF/AIPN.

KEYWORDS
bleeding, immature platelet, immune thrombocytopenia, reticulated

1 INTRODUCTION patients, even those with severe thrombocytopenia.3–6 For unknown

Immune thrombocytopenia (ITP) is a significant cause of severe throm-
bocytopenia in pediatric patients but remains a diagnosis of exclusion.1
It is crucial to appropriately differentiate ITP from bone marrow fail-
ure (BMF) syndromes or malignancy, which generally carry a higher
risk of bleeding at any given platelet count and differ in treatment
recommendations.2 Due to the lower bleeding risk in ITP, current evi-
dence and recommendations support observation in the majority of
Abbreviations: AIPN, absolute immature platelet number; BMF, bone marrow failure; IPF,
immature platelet fraction; ITP, immune thrombocytopenia; RP, reticulated platelet
reasons, however, some patients with ITP will experience severe bleed-
ing and require treatment.7 Beyond the platelet count, which corre-
lates imperfectly with bleeding, risk factors for severe bleeding are not
well established.5–8
The immature platelet fraction (IPF) is an emerging laboratory
test for measuring platelet production/turnover. IPF measurement
is an automated process resulting in values that correlate with
nonautomated measurements of reticulated platelets (RPs).9,10
RPs are young platelets containing residual RNA, and an increase
in RPs suggests increased thrombopoiesis.11 Some studies have
suggested that IPF, as expected, increases in diseases of peripheral

Pediatr Blood Cancer. 2017;e26812. wileyonlinelibrary.com/journal/pbc 

c 2017 Wiley Periodicals, Inc. 1 of 6
https://doi.org/10.1002/pbc.26812
2 of 6
destruction such as ITP.12–16 In contrast, the IPF should be normal or
low in BMF, where the bone marrow is not able to increase platelet
production.
Immature platelets are thought to be more hemostatic17 and
thus an increased IPF or absolute immature platelet number
(AIPN = platelet count x IPF/0.1) might contribute to why patients
with ITP are at a lower relative risk of bleeding than patients with
BMF even at the same platelet count. There is recent evidence that
AIPN alone, regardless of platelet count, is the best predictor of
bleeding in adult patients with thrombocytopenia due to hematologic
malignancies.18 A similar, limited study of a small number of pediatric
patients with ITP found a strong inverse correlation between AIPN
and bleeding score.19 These results suggest that a lower relative AIPN
in an ITP patient may be a potential marker for bleeding risk. However,
the role of immature platelets in hemorrhage is still unclear, as IPF%
did not significantly correlate with bleeding severity in these patients
and other studies have found a higher IPF% to be associated with more
severe bleeding.19,20
To address some of the limitations of this conflicting evidence, we
examined a large cohort of patients with thrombocytopenia and a mea-
sured IPF (n = 272) with two main goals: to examine the ability of IPF
to help distinguish patients with BMF from ITP in their initial presenta-
tion with thrombocytopenia and to determine whether the IPF or AIPN
could identify a subset of patients with ITP who were at increased risk
of significant bleeding.
2 METHODS
The protocol was approved by the institutional review board.
2.1 Study population
We performed a retrospective chart review of all patients with throm-
bocytopenia, defined as a platelet count <50 × 109 /l, and an IPF
measured at the Children's Hospital of Philadelphia between Novem-
ber 1, 2013 and July 1, 2015. Patients of age 2 months–21 years
were included. For patients with multiple measurements, only the first
CBC to meet the study inclusion criteria within the study period was
included. Each patient chart was reviewed for the correct diagnosis
causing the thrombocytopenia as well as for bleeding symptoms and
for subsequent treatment of bleeding. Patients were excluded if the
cause of thrombocytopenia was indeterminate.
2.2 Demographic and clinical data
Demographic and clinical data were collected on each patient by
reviewing medical and laboratory records. These variables included
age, gender, race, date of diagnosis, other diagnoses, and bleeding
episodes that caused the patient to seek medical attention, need for
platelet raising therapy due to bleeding symptoms, and laboratory
results including CBC and IPF.
Causes of thrombocytopenia were categorized as ITP, BMF, malig-
nancy or other. Patients with ITP were further subcategorized as
MCDONNELL ET AL .
acute (<3 months), persistent (3–12 months), or chronic (>12 months)
based on the duration of thrombocytopenia at the time of the
CBC.
2.3 IPF measurement
IPF data were measured by the Sysmex XN3000 hematology ana-
lyzer (Sysmex Corporation, Kobe, Japan). For patients with multiple
IPF measurements, the first IPF was utilized. AIPN was then calculated
using the concurrent platelet count and the IPF.
2.4 Bleeding scoring
Bleeding symptoms within 24 hr of the IPF measurement were deter-
mined by review of the medical record and scored on a scale of 0–5
using the Buchanan and Adix overall bleeding severity score.8 A single
investigator (AM) not blinded to patient lab results assigned bleeding
scores based on chart review of each patient, although the bleeding
scores were confirmed by review of the records in a subgroup of the
patients by a second investigator who was blinded to the initial bleed-
ing score (KB or ML). Scores were determined by reviewing bleeding
signs/symptoms occurring within 24 hr of the IPF measurement, which
were documented in the subjective, physical exam, assessment, and
plan sections of the most recent progress note. Whether the patient
ever required medical attention and/or treatment for bleeding during
the study period was also recorded.
2.5 Statistical analysis
Data were analyzed using GraphPad Prism, version 6.0 (GraphPad
Softward, La Jolla, CA) and STATA v.11 (Stata Corp., College Station,
TX). Descriptive statistics were used to summarize demographic and
clinical data. Differences in two or more patient groups were analyzed
using the nonparametric Wilcoxon rank-sum test or Kruskal–Wallis
test, respectively. Receiver operator characteristic (ROC) analysis was
utilized to determine the IPF value that differentiates ITP from BMF
and an IPF value in ITP patients that is associated with a higher likeli-
hood of coming to medical attention for severe bleeding and requiring
platelet raising therapy. Odds ratios of coming to medical attention for
bleeding and requiring platelet raising therapy for bleeding based on
IPF were calculated and analyzed using Fishers exact test. Statistical
significance was established at P < 0.05.
The independent association between having a bleeding score >3
and an IPF cutoff <10.4% was explored using multivariate logistic
regression. This IPF cutoff of 10.4% was chosen because this was
the 25%tile for the ITP cohort. The following potential confounding
variables were included in the analysis: platelet count (categorized
as either above or below 10,000/mcl); age categorized as <5 years,
5–10 years, and >10 years; sex; and whether the patient had acute,
persistent, or chronic ITP at the time of the CBC. Interaction terms
identified during the stratified analysis were included in the multivari-
ate logistic regression model in order to evaluate their statistical sig-
nificance. Stratum-specific odds ratios (ORs) were calculated for com-
binations of factors with significant interactions.
MCDONNELL ET AL . 3 of 6

TA B L E 1 Summary of cohort demographics and laboratory data

ITP Bone marrow failure Malignancy Other All

Number of patients 97 (36%) 11 (4%) 126 (46%) 38 (14%) 272 (100%)
Age (years) 5 (0.3–20) 9 (7–14) 8 (0.3–21) 4 (0.2–19) 7 (0.2–21)
Sex
Female 46 (47%) 7 (64%) 59 (47%) 23 (61%) 135 (49.6%)
Platelet count 11 (1–48) 12 (5–42) 20 (1–49) 31 (3–49) 16.5 (1–49)
IPF 17.5 (0.2–50.5) 2.8 (1.5–7.7) 3.2 (0.2–37.5) 8.7 (0.5–49.8) 6.7 (0.2–50.5)

Data presented as median (range) or count (% of total).

than in patients with malignancy or other causes of thrombocytopenia

(P < 0.0001 for each, Fig. 1A). IPF was significantly higher in patients
with ITP than patients with BMF (17.5% vs. 2.8%, P < 0.001, Fig. 1B).
An ROC curve to analyze the ability of IPF to discriminate between
ITP and BMF (Fig. 1C) demonstrates that with a cut-off of 5.2%, there is
a 93% sensitivity and a 91% specificity for ITP. A similar analysis with all
subjects showed that the best specificity and sensitivity for ITP was at
IPF > 8.45% with sensitivity of 80.4% and specificity of 79.9% (Fig. 1D);
however, there was some significant overlap of ranges of values seen in
congenital thrombocytopenia syndromes, malignancy, and ITP.

3.3 IPF over the course of ITP illness

F I G U R E 1 Distribution of platelet count (A) and immature platelet
fraction (B) across diagnoses. Depicted boxes represent medians with
range. (C) ROC curve predicting the sensitivity and specificity of IPF to
distinguish ITP from BMF. (D) Same as (C) but for ITP versus all throm-
bocytopenia
3 RESULTS
In our patient population, the platelet count was significantly lower
in patients with acute ITP that resolved in less than 3 months than
in patients whose ITP was chronic or persistent (P = 0.0047 and
P = 0.0034, Fig. 2A), but the IPF did not differ based on duration of ill-
ness (P = 0.3731, Fig. 2B). The bleeding severity score also did not sig-
nificantly differ between patients with acute, persistent, and chronic
ITP (P = 0.1156, Fig. 2C).
When divided by treatment status, the cohort consisted of 88
patients without ITP treatment and nine patients with ITP treatment.
Patients treated for ITP had a higher mean platelet count (P = 0.01)
than patients without, but there was no significant difference in IPF
between these two groups (P = 0.58).

3.1 Subject characteristics

A total of 272 patients met inclusion criteria, including 97 with ITP, 11
with BMF, 126 with malignancy, and 38 with other causes of thrombo-
cytopenia (Supplementary Fig. S1). Demographics and laboratory data
are displayed in Table 1. For 64 of 73 newly diagnosed patients with
ITP, the initial IPF was sent within 1 week of diagnosis. Ten patients
had chronic ITP at the time of first IPF measurement, and eight patients
were persistent. The remaining six patients had IPF measured at recur-
rence of ITP.
3.2 Using IPF to distinguish ITP from BMF and other
causes of thrombocytopenia
Although the median platelet count and IPF differed significantly
between groups (P < 0.001 for each, Fig. 1), it was not different
when comparing ITP (11 × 109 /L (1–48)) and BMF (12 × 109 /l
P = 0.59). The platelet count in ITP patients was significantly lower
3.4 IPF as predictor of bleeding in ITP
Of the 97 total patients with ITP, 10 patients had an overall bleed-
ing severity score of 0, or no signs of hemorrhage, at the time of IPF
measurement. There were 53 patients with a score of 1 or 2, indicat-
ing minor to mild skin manifestations including bruising and petechiae,
and 26 patients with a score of 3, indicating overt mucosal bleeding
that did not require immediate medical attention or intervention. A
total of eight patients were scored at 4 or 5, which indicates mucosal
bleeding or suspected internal bleeding that required immediate med-
ical attention or life-threatening or fatal hemorrhage at any site. The
single patient with life-threatening hemorrhage in this cohort had a GI
bleed that required red cell and platelet transfusion following a lack of
response to intravenous immune globulin (Fig. 3A).
The platelet count of patients with no signs of bleeding or minor skin
(5–42), bleeding was significantly higher than patients with mild to moderate
bleeding (18 × 109 /l vs. 6.0 × 109 /l, P < 0.0001, Fig. 3B) and severe to
4 of 6 MCDONNELL ET AL .

FIGURE 2 Platelet count (A), IPF% (B), and overall bleeding severity (C) stratified by duration of patient illness

TA B L E 2 Univariate analysis: factors associated with a bleeding

score >3

Clinical factor Odds ratio (95% CI) P-value

Low IPF (<10.4%) 3.3 (1.2–8.6) 0.02
Platelet count <10,000/mcl 4.8 (2–11.9) 0.001
Age category (reference 5–10 years)
<5 years 0.5 (0.1–1.4) 0.3
>10 years 0.6 (0.2–2) 0.4
Female 0.9 (0.4–1.9) 0.6
Disease status (reference persistent)
Acute 1.7 (0.3–9.2) 0.5
Chronic 1.3 (0.2–10.5) 0.8

IPF, immature platelet fraction.

F I G U R E 3 (A) Distribution of bleeding severity scores in ITP patients

in our cohort. (B–D) Association of platelet count (B), IPF (C), and AIPN TA B L E 3 Multivariate analysis: factors associated with a bleeding
(D) with overall bleeding severity scores in patients with ITP. Results score >3
shown are medians with range Clinical factor Odds ratio (95% CI) P-value
Low IPFa
Platelet count > 10,000/mcl 1.9 (0.4–9.6) 0.5
life-threatening hemorrhage (18 × 109 /l vs. 4.0 × 109 /l, P = 0.0016).
The platelet count did not differentiate between patients with mild Platelet count <10,000/mcl 17.4 (3.6–83.4) <0.001

to moderate bleeding from those with severe to life-threatening hem- High IPFa

orrhage (P = 0.4136); however, the median IPF in these two groups Platelet count <10,000/mcl 4.4 (1.4–13.5) 0.01
was significantly different (5.35% vs. 19.0%, P = 0.0015). The AIPN Age category
differentiated all three bleeding severity groups (Fig. 3C). The median <5 years 0.5 (0.1–1.8) 0.3
AIPN of patients with no bleeding or minor bleeding was 3.250 × 109 /l, >10 years 1.1 (0.3–4.5) 0.8
which was significantly higher than the median AIPN of 1.150 × 109 /l Female 0.9 (0.1–4.9) 0.7
in patients with mild to moderate bleeding (P < 0.0001). Furthermore, Disease status
the mild to moderate bleeding group had a significantly higher median
Acute 0.8 (0.1–4.9) 0.8
AIPN than the severe to life-threatening hemorrhage group, which had
Chronic 1.1 (0.1–9.4) 0.9
a median AIPN of 0.205 × 109 /l (P = 0.0136). ROC analysis of AIPN
a
The odds ratio for IPF (immature platelet fraction) cannot be reported indi-
found that at AIPN < 0.695 × 109 /l, there is an 87.5% sensitivity and
vidually because of evidence of effect modification by platelet count. Only
79.8% specificity for severe or life-threatening hemorrhage. stratum-specific values are reported. The reference is high IPF (>10.4%)
Tables 2 and 3 provide the results of the univariate and multivari- and platelet count > 10,000/mcl.
ate logistic regression analysis. On univariate analysis only a low IPF
(<10.4%) and a low platelet count (<10 × 109 /L) were found to be asso-
ciated with an increased bleeding score. On multivariate analysis there
was a statistically significant interaction between IPF and platelet score >3 while a high IPF (>10.4%) with a platelet count <10 × 109 /l
count; as a consequence, only stratum-specific OR can be reported. A had a lower risk OR (4.4 (1.4–13.5)). Conversely, a low IPF associated
low IPF (<10.4%) combined with a platelet count <10 × 109 /l was asso- with a platelet count >10 × 109 /l was not associated with an increased
ciated with the highest risk (OR 17.4 (3.6–83.4)) of having a bleeding bleeding score.
MCDONNELL ET AL .
4 DISCUSSION
Our results indicate that in a patient presenting with isolated thrombo-
cytopenia, an elevated IPF provides useful supportive data for the diag-
nosis of ITP, consistent with other significantly smaller studies.15,16
In our cohort, the IPF was adequately sensitive and specific to differ-
entiate ITP from BMF at IPF > 5.2%. This threshold is lower than a
previously reported cut-off of 9.4%, which was found to differentiate
patients with ITP from patients with thrombocytopenia on chemother-
apy used as a control group to represent bone marrow suppression.16
The lower range of IPF values observed in our BMF cohort likely
reflects the fact that noniatrogenic BMF patients are unlikely to be in a
recovery phase of illness compared with patients on chemotherapy.16
Furthermore, in our cohort, the IPF did not differ significantly based on
length of illness, indicating that the IPF is potentially useful for diagnos-
tic purposes when patients present with thrombocytopenia of unclear
duration.
The most important finding in our study is that both IPF and AIPN
are better predictors of significant bleeding risk in patients with ITP
than platelet count in a large cohort of patients with ITP. Higher total
platelet count may protect against mild bleeding, but at lower platelet
counts it appears to be the immature platelets that protect against
severe and life-threatening hemorrhage. This finding held true on mul-
tivariate analysis where IPF was confirmed as a modifier of bleeding
risk but only when the platelet count was <10 × 109 /l. A previous
small study by Greene et al. suggested that in pediatric patients with
platelet counts under 30 × 109 /l, there was a strong inverse correlation
between AIPN and acute bleeding score. Those with AIPN > 5.5 × 109 /l
did not experience anything more than cutaneous bleeding, unrelated
to platelet count.19 Likewise, a prospective study of bleeding risk in
adults with thrombocytopenia due to hematologic malignancies found
that a rise in AIPN of 0.5 × 109 /l decreased the odds of any bleed-
ing within 1 day by 26% and AIPN > 2 × 109 /l had a 100% negative
predictive value for severe bleeding.18 These previous studies demon-
strated the predictive value of AIPN in the next 1–2 days; however,
our results suggest that a single measure of IPF or AIPN at diagno-
sis may have predictive value for risk of bleeding for an even longer
period of time, perhaps because in ITP the IPF is fairly stable over time.
Our finding is significant because there are currently few predictors of
hemorrhage in ITP7 and our results suggest that IPF or AIPN is the
best laboratory predictor identified to date. This is a simple labora-
tory test and its value is that it can help guide prophylactic therapy
decisions.
Multiple mechanisms of lower relative number of immature
platelets have been proposed, including marrow suppression, ineffec-
tive thrombopoiesis, increased reticuloendothelial clearance of imma-
ture platelets, and increased complement-mediated cytolysis of imma-
ture platelets.19,21 One plausible explanation is that in patients with
low AIPN, there may be specific autoantibodies targeting megakary-
ocytes that are different than the autoantibodies produced by patients
with high AIPN. For example, anti-GPIb/IX antibodies have been asso-
ciated with increased risk of development of chronic ITP in some
studies, resistance to therapy, and increased risk of bleeding.22 It is
unknown if patients with anti-GPIb/IX antibodies have reduced AIPN;
5 of 6
however, GPIb/IX is expressed on the surface of megakaryoctyes23
and presence of these antibodies in plasma has been shown to
suppress megakaryocyte production in vitro.24,25 Further studies
will need to be done to elucidate the pathophysiologic differences
between ITP patients with high and low AIPN and better understand
why platelets falling in the IPF gate appear to protect from severe
hemorrhage.
This study was limited due to its retrospective design. The quality
of documentation of bleeding symptoms and physical exam varied sig-
nificantly and therefore clinically significant bleeding may have been
missed in the chart review because of the lack of documentation of
these symptoms/signs. Treatment thresholds are also inherently sub-
jective, vary by physician, and may influence the way the bleeding man-
ifestations are documented. Patients in our cohort were at different
stages of their illness and may or may not have received treatment
prior to measurement of first available IPF. All of the analysis is retro-
spective, but suggests that IPF may be useful in differentiating patients
at high risk of bleeding from those who are unlikely to have signifi-
cant bleeding; this would need to be confirmed in a prospective study.
Finally, as is true with most ITP cohorts, the majority of patients did not
have severe or life-threatening hemorrhage so the number of bleeding
events is small.
In conclusion, our single-center retrospective study in a relatively
large cohort of pediatric patients with ITP demonstrated that IPF mea-
surement may have utility in both diagnosis of ITP and prediction of
relative future risk of bleeding in ITP patients. Use of IPF may prevent
more invasive testing, such as bone marrow biopsy in patients where
the diagnosis of ITP is less clear. Using the IPF to calculate AIPN at
diagnosis may be a more accurate way to predict bleeding risk, coun-
sel patients, and determine which patients to prophylactically treat to
prevent severe hemorrhage. Future research to prospectively validate
these findings, better understand the physiology of immature platelets,
and clarify the pathophysiology of ITP in patients with a relatively low
IPF/AIPN is necessary.
CONFLICT OF INTEREST
M.L. has been a consultant for GSK and Novartis and has received
research funding from AstraZeneca and the National Institute of
Health, National Institute of Allergy and Infectious Disease. The other
authors declare no relevant conflict of interest.
ORCID
Michele P. Lambert http://orcid.org/0000-0003-0439-402X
REFERENCES
1. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of termi-
nology, definitions and outcome criteria in immune thrombocytopenic
purpura of adults and children: report from an international working
group. Blood 2009;113(11):2386–2393.
2. Norfolk DR, Ancliffe PJ, Contreras M, et al. Consensus Conference on
Platelet Transfusion, Royal College of Physicians of Edinburgh, 27–
28 November 1997. Synopsis of background papers. Br J Haematol.
1998;101(4):609–617.
6 of 6
3. Neunert C, Lim W, Crowther M, et al. The American Society of Hema-
tology 2011 evidence-based practice guideline for immune thrombo-
cytopenia. Blood. 2011;117(16):4190–4207.
4. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic
purpura: a practice guideline developed by explicit methods for the
American Society of Hematology. Blood 1996;88(1):3–40.
5. Dickerhoff R, von Ruecker A. The clinical course of immune throm-
bocytopenic purpura in children who did not receive intravenous
immunoglobulins or sustained prednisone treatment. J Pediatr
2000;137(5):629–632.
6. Blanchette V, Carcao M. Approach to the investigation and manage-
ment of immune thrombocytopenic purpura in children. Semin Hematol
2000;37(3):299–314.
7. Neunert C, Noroozi N, Norman G, et al. Severe bleeding events in
adults and children with primary immune thrombocytopenia: a sys-
tematic review. J Thromb Haemost. 2015;13(3):457–464.
8. Buchanan GR, Adix L. Grading of hemorrhage in children with idio-
pathic thrombocytopenic purpura. J Pediatr. 2002;141(5):683–688.
9. Pons I, Monteagudo M, Lucchetti G, et al. Correlation between imma-
ture platelet fraction and reticulated platelets. Usefulness in the eti-
ology diagnosis of thrombocytopenia. Eur J Haematol 2010;85(2):158–
163.
10. Seo A, Yuan D, Daniels S, et al. Reference intervals for immature
platelet fraction and immature platelet count. Int J Lab Hematol.
2015;37(1):e1–e2.
11. Hoffmann Johannes JML. Reticulated platelets: analytical aspects and
clinical utility. Clin Chem Lab Med. 2014;52:1107.
12. Briggs C, Kunka S, Hart D, et al. Assessment of an immature
platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol
2004;126(1):93–99.
13. Strauss G, Vollert C, von Stackelberg A, et al. Immature platelet count:
a simple parameter for distinguishing thrombocytopenia in pediatric
acute lymphocytic leukemia from immune thrombocytopenia. Pediatr
Blood Cancer. 2011;57(4):641–647.
14. Jung H, Jeon HK, Kim HJ, et al. Immature platelet fraction: establish-
ment of a reference interval and diagnostic measure for thrombocy-
topenia. Korean J Lab Med. 2010;30(5):451–459.
15. Sakuragi M, Hayashi S, Maruyama M, et al. Clinical significance of
IPF% or RP% measurement in distinguishing primary immune throm-
bocytopenia from aplastic thrombocytopenic disorders. Int J Hematol.
2015;101(4):369–375.
16. Adly AA, Ragab IA, Ismail EA, et al. Evaluation of the immature platelet
fraction in the diagnosis and prognosis of childhood immune thrombo-
cytopenia. Platelets. 2015;26(7):645–650.
17. Fager AM, Wood JP, Bouchard BA, et al. Properties of pro-
coagulant platelets defining and characterizing the subpopulation
MCDONNELL ET AL .
binding a functional prothrombinase. Arterioscler Thromb Vasc Biol
2010;30(12):2400–2407.
18. Estcourt LJ, Stanworth SJ, Harrison P, et al. Prospective observa-
tional cohort study of the association between thromboelastome-
try, coagulation and platelet parameters and bleeding in patients
with haematological malignancies—the ATHENA study. Br J Haematol
2014;166(4):581–591.
19. Greene LA, Chen S, Seery C, et al. Beyond the platelet count:
immature platelet fraction and thromboelastometry correlate with
bleeding in patients with immune thrombocytopenia. Br J Haematol
2014;166(4):592–600.
20. Frelinger AL, 3rd, Grace RF, Gerrits AJ, et al. Platelet function tests,
independent of platelet count, are associated with bleeding severity in
ITP. Blood 2015;126(7):873–879.
21. Peerschke EIB, Andemariam B, Yin W, et al. Complement activation on
platelets correlates with a decrease in circulating immature platelets
in patients with immune thrombocytopenic purpura. Br J Haematol
2010;148(4):638–645.
22. Hou M, Stockelberg D, Kutti J, et al. Antibodies against platelet
GPIb/IX, GPIIb/IIIa, and other platelet antigens in chronic idiopathic
thrombocytopenic purpura. Eur J Haematol 1995;55(5):307–314.
23. Vainchenker W, Deschamps J, Bastin J, et al. Two monoclonal
antiplatelet antibodies as markers of human megakaryocyte matura-
tion: immunofluorescent staining and platelet peroxidase detection in
megakaryocyte colonies and in in vivo cells from normal and leukemic
patients. Blood. 1982;59(3):514–521.
24. Chang M, Nakagawa PA, Williams SA, et al. Immune thrombocytopenic
purpura (ITP) plasma and purified ITP monoclonal autoantibodies
inhibit megakaryocytopoiesis in vitro. Blood. 2003;102(3):887–895.
25. McMillan R, Wang L, Tomer A, et al. Suppression of in vitro megakary-
ocyte production by antiplatelet autoantibodies from adult patients
with chronic ITP. Blood. 2004;103(4):1364–1369.
SUPPORTING INFORMATION
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How to cite this article: McDonnell A, Bride KL, Lim
D, Paessler M, Witmer CM, Lambert MP. Utility of the
immature platelet fraction in pediatric immune thrombocy-
topenia: Differentiating from bone marrow failure and pre-
dicting bleeding risk. Pediatr Blood Cancer. 2017;00:e26812.
https://doi.org/10.1002/pbc.26812