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Hematology

ISSN: 1024-5332 (Print) 1607-8454 (Online) Journal homepage: http://www.tandfonline.com/loi/yhem20

Characteristics and management of primary


and other immune thrombocytopenias: Spanish
registry study

Javier Palau, Esther Sancho, Magdalena Herrera, Sol Snchez, Mara Eva
Mingot, Rosa Isabel Upegui, M Jos Rodrguez Salazar, Ftima de la Cruz,
M Cristina Fernndez, Toms Jos Gonzlez Lpez, Jos Julio Hernndez,
Eduardo Ros, M Fernanda Lpez-Fernndez, Marta Garca, Jos-ngel
Hernndez & Miguel A. Sanz

To cite this article: Javier Palau, Esther Sancho, Magdalena Herrera, Sol Snchez, Mara
Eva Mingot, Rosa Isabel Upegui, M Jos Rodrguez Salazar, Ftima de la Cruz, M Cristina
Fernndez, Toms Jos Gonzlez Lpez, Jos Julio Hernndez, Eduardo Ros, M Fernanda
Lpez-Fernndez, Marta Garca, Jos-ngel Hernndez & Miguel A. Sanz (2017): Characteristics
and management of primary and other immune thrombocytopenias: Spanish registry study,
Hematology, DOI: 10.1080/10245332.2017.1311442

To link to this article: http://dx.doi.org/10.1080/10245332.2017.1311442

Accepted author version posted online: 31


Mar 2017.
Published online: 17 Apr 2017.

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Download by: [Orta Dogu Teknik Universitesi] Date: 19 April 2017, At: 01:51
HEMATOLOGY, 2017
http://dx.doi.org/10.1080/10245332.2017.1311442

Characteristics and management of primary and other immune


thrombocytopenias: Spanish registry study
Javier Palaua, Esther Sanchob, Magdalena Herrerac, Sol Snchezd, Mara Eva Mingot e, Rosa Isabel Upeguif,
M Jos Rodrguez Salazarg, Ftima de la Cruzh, M Cristina Fernndezi, Toms Jos Gonzlez Lpezj, Jos
Julio Hernndezk, Eduardo Ros l, M Fernanda Lpez-Fernndezm, Marta Garcan, Jos-ngel Hernndezo
and Miguel A. Sanza,p
a
Hospital Universitario y Politcnico la Fe, Valencia, Spain; bHospital Vall dHebron, Barcelona, Spain; cHospital La Candelaria Tenerife, Spain;
d
Fundacin Jimnez Daz, Madrid, Spain; eHospital Carlos Haya, Mlaga, Spain; fHospital Arnau de Vilanova, Lleida, Spain; gHospital
Universitario de Canarias, La Laguna, Spain; hHospital Virgen del Roco, Sevilla, Spain; iHospital de Cabuees, Gijn, Spain; jHospital
Universitario Burgos, Burgos, Spain; kHospital de San Eloy, Barakaldo, Spain; lHospital Universitario Virgen de Valme, Sevilla, Spain;
m
Complejo Hospitalario Universitario A Corua, A Corua, Spain; nHospital Consorci Sanitari de Terrassa, Terrassa, Spain; oHospital
Universitario Infanta Leonor, Madrid, Spain; pDepartamento de Medicina, Universidad de Valencia, Spain

ABSTRACT KEYWORDS
Background: The natural history and its modulation by treatments administered for immune Immune thrombocytopenia;
thrombocytopenia (ITP) in the clinical practice remains unknown. In addition, little platelet count; response;
information is available on the characteristics and management of ITP in Spain. corticosteroids; intravenous
immunoglobulins
Methods: We conducted an observational, multicenter, registry in 70 Hematology Services from
Spain between 2009 and 2011, which included children from 2 months of age and adults with
primary ITP or another ITP diagnosed within the last 6 months (platelet count [PC] < 100 109/l).
Patients were followed-up at 6 and 12 months.
Results: 484 patients were included (median [Q1, Q3] age 52 [29,74] years, 87.6% adults), 56%
women, 10.5% with secondary ITP. Median (Q1, Q3) PC at diagnosis was 12 109/l (4, 32); 72% of
patients had bleeding symptoms (62% cutaneous bleeding, 29% oral cavity bleeding, 18%
epistaxis). 81% of patients with primary ITP received first-line treatment, mainly with
corticosteroids (>6 weeks in 59% of cases), either alone (41%) or associated with intravenous
immunoglobulin (33%). The response (30 109/L) to first-line treatment was 92%. A total of
19% of patients received second-line treatment and 6% additional treatments. At 12 months,
74% of primary ITP patients maintained a PC 100 109/L in absence of treatment (10% still
had hemorrhagic manifestations).
Conclusions: Characteristics of Spanish ITP patients are comparable to those from other
countries. Although a high response rate to first-line treatments is observed, at 1 year, the
disease persists in around one quarter of patients. Overall therapeutic management in Spain
conforms to current recommendations, except for an excessive duration of corticosteroids
therapy.

Introduction
years, with even higher values in patients of both
Primary immune thrombocytopenia (primary ITP, for- sexes older than 60 years [4,5].
merly known as idiopathic thrombocytopenic Since there is no specific diagnostic technique, the
purpura) [1] is an autoimmune disorder present in diagnosis must be made by exclusion of other causes
both sexes and in both childhood and adulthood. of thrombocytopenia, giving uncertainty about
Although ITP has been a well-known hematologic dis- whether it is a primary or a secondary ITP. Secondary
order for more than two centuries, some aspects ITPs are a group of immune-mediated thrombocytope-
regarding etiologic factors or clinical behavior still nias associated to either an underlying disease (such as
remain unknown. The availability of epidemiological lupus erythematosus, or infections caused by human
data on primary ITP is very limited and there is no immunodeficiency virus (HIV), Helicobacter pylori, etc.)
specific data from Spain. Prevalence of ITP has been or to drug exposure [1].
reported ranging from 4.5 to 10.5 cases per 100,000 ITP is characterized by a low platelet count due to an
persons in adults [2] and 4.6 cases per 100,000 in chil- increased destruction mediated by antiplatelet anti-
dren [3]. In the adult population, annual incidences bodies and a concomitant submaximal production
between 16 and 27 new patients per million have [612]. The main features are the appearance of
been reported, predominantly in women aged 3059 petechiae, ecchymosis and not-clinically relevant

CONTACT Miguel A. Sanz miguel.sanz@uv.es Department Hematology, Valencia University Medical School, University Hospital La Fe, (Torre F, Planta 7),
Avinguda Fernando Abril Martorell, 106, Valencia ES-46026, Spain
2017 Informa UK Limited, trading as Taylor & Francis Group
2 J. PALAU ET AL.

hemorrhages. However, there is a risk of serious bleed- independently of the clinical evolution of the disease.
ings and fatal intracranial hemorrhages, which In case of premature discontinuation for any reason,
increases at platelet counts below 510 109/l [5,13]. investigators had to complete the last available infor-
Treatment of patients with ITP is primarily aimed at mation of the patient status. The following data were
reaching a platelet count high and stable enough to retrospectively collected from the medical records at
prevent the occurrence of serious bleeding. The each study visit through a web-based system using a
optimal treatment of ITP has not been yet established, secure internet server: clinical history and ITP etiology
and currently multiple drugs and other therapeutic (only at baseline visit), bleeding symptoms over the
approaches as splenectomy are being used, with vari- previous 6 months of each visit, primary ITP treatment
able responses. In addition, until the publication of and response. Response criteria were set according to
the randomized controlled trials demonstrating the the standardization of Rodeghiero et al. [1]: complete
efficacy of thrombopoietin analogues (romiplostim response, platelet count 100 109/l; partial response,
and eltrombopag) [1416], the efficacy of the most fre- platelet count 30 and <100 109/l, and at least
quently used ITP treatments was unclear, since the double the baseline value; no response: platelet
majority of data came from non-randomised studies count <30 109/l or less than twice the baseline. The
or case series [1723]. In 1996, the American Society overall response rate (complete plus partial response)
of Hematology published the first ITP practice guide- was described together with its 95% confidence
lines [24]. These recommendations on ITP diagnosis interval.
and management were updated in 2010 by an inter- Sample size (500 patients) was calculated to achieve
national consensus panel [25], which were immediately a precision of 2% for describing an attribute estimate
adapted to Spain, with the aim to unify the criteria with an expected proportion of 6% in the study popu-
across centres [26]. lation and a 95% confidence interval, assuming that the
Given the multiple controversies and uncertainties overall number of prevalent ITP cases in Spain is
in ITP, the present epidemiological registry study around 5000 [2,27,28].
was designed to know the reality of the disease in a Descriptive analyses were provided for each variable
large number of Spanish institutions with the aim of at all the study visits. Statistical analyses were per-
establishing, in successive phases of the project, a formed with the SPSS statistical package (Chicago, IL,
plan to standardize care practices. The main objec- U.S.A.) version 21.0.
tives were: to describe the clinical characteristics
and diagnostic procedures in patients with ITP; to
describe the therapeutic management of primary ITP Results
in the clinical practice; to describe the response rate
Characteristics of patients with immune
to each line of treatment in primary ITP patients;
thrombocytopenia
and to compare our results with data from other pub-
lished ITP cohorts. A total of 484 patients from 70 Spanish hospitals were
included in the study between 1 July 2009 and 30
November 2011. Of them, 361 (74.6%) were completely
Patients and methods
followed-up during 12 months (Figure 1).
The TIMES study was an epidemiological, observa- Table 1 shows the main socio-demographic and
tional, prospective, multicenter, registry study con- clinical characteristics of the study cohort.
ducted in Hematology Services across Spain. The Most patients (87.6%) were adults, with a median
inclusion criteria were: children from 2 months of age age of 52 and 58 years in primary and secondary ITP,
and adults; presumptive diagnosis of primary ITP or respectively, and 55 and 62% were women, respect-
another ITP diagnosed within the last 6 months; plate- ively. Secondary ITP was diagnosed in 10.5% (n = 51)
let count <100 109/l at ITP diagnosis. A presumptive of patients, with a wide variability in associated dis-
diagnosis of ITP was established when the history, orders. Systemic lupus erythematosus (9/51 cases,
physical examination, complete blood count, and 17.6%) and lymphoproliferative syndromes (17.6%)
examination of the peripheral blood smear did not were the most common underlying diseases, followed
suggest other etiologies for the thrombocytopenia. by infections (Table 1).
To minimize sample bias, all consecutive patients The most common comorbidity was hypertension,
attending the participating clinics who fulfilled eligi- followed by recent infection, cardiovascular disease
bility criteria were invited to participate. The protocol and diabetes. A total of 5.2% of patients had received
was approved by an independent ethics committee, drugs possibly related to ITP.
and all patients gave their written informed consent Median platelet count at baseline was below 30
before enrollment. 109/l in three quarters of primary ITP patients and
The study included a baseline visit at the beginning below 50 109/l in three quarters of secondary ITP
and two follow-up visits at 6 and 12 months, patients (Table 1).
HEMATOLOGY 3

Figure 1. Study flow-chart.

Diagnostic procedures was: oral cavity bleedings, 3.1 (180); gastrointestinal


bleedings, 3.1 (20); cutaneous bleeding, 1.8 (30); epi-
Figure 2 shows the main diagnostic procedures per-
staxis, 1.5 (5); hematuria, 1.9 (7); muscle hematoma,
formed in addition to the initial blood count. The
1.3 (5); metrorrhagia, 1.4 (2); and intracranial haemor-
most commonly performed tests in both primary and
rhage, 1.2 (2). In patients with secondary ITP these
secondary ITP populations were hepatitis B virus
figures were: oral cavity bleedings, 1.8 (4); gastrointes-
(HBV) serology (87 and 92% of patients, respectively),
tinal bleedings, 1.6 (3); cutaneous bleeding, 2.5 (10);
HIV serology (86 and 92%), hepatitis C virus (HCV) ser-
epistaxis, 2 (4); hematuria, 1 (1); metrorrhagia, 3 (5);
ology (83 and 92%) and antinuclear antibodies (77 and
and intracranial haemorrhage, 1 (1).
82%).
The highest percentage of positive results was
observed for antinuclear antibodies in both popu-
lations (14% in primary and 37% in secondary ITP Therapeutic management of primary ITP
patients), followed by Helicobacter pylori in primary Figure 3 and Table 2 summarize the main character-
ITP patients (13%) and by HBV serology in secondary istics of therapeutic management in the subgroup of
ITP patients (18%) (Figure 2). Platelet-associated anti- primary ITP patients (n = 433).
bodies test was performed in 21% of primary ITP Observation only was preferred in 18.9% of de novo
patients and in 41% of secondary ITP patients. diagnosed patients. None of them required treatment
later on (Figure 3).
The remaining 81.1% of patients received first-line
Clinical manifestations at diagnosis
treatment: 41.3% of patients received one drug,
Clinical manifestations at diagnosis were observed in 31.6% received two drugs, 6.0% received three drugs
72% of patients with primary ITP and 67% of patients and 2.2% received four to five drugs. No splenectomies
with secondary ITP, mainly cutaneous (61 and 63%, were performed in the first-line setting.
respectively) and oral cavity bleedings (29 and 24%), The most common first-line drugs were corticoster-
and epistaxis (17 and 24%). Potentially severe bleed- oids as monotherapy (40.6%) or combined with IVIg
ings were rare (gastrointestinal bleedings 4 and 14%, (32.8%). 5.8% of patients received IVIg. Patients who
intracranial haemorrhage 1 and 2%). Other bleeding received these treatments had lower platelet counts
symptoms included muscle hematoma (6 and 0%), at baseline and more bleeding symptoms than patients
metrorrhagia (5 and 4%) and hematuria (2 and 6%). who were not treated at all (Table 3).
At diagnosis, the mean (maximum) number of epi- Prednisone was the most commonly used corticos-
sodes for each symptom in patients with primary ITP teroid (65.1%), followed by methylprednisolone
4 J. PALAU ET AL.

Table 1. Characteristics of de novo diagnosed patients with immune thrombocytopenia (ITP) in Spain between 2009 and 2011.
Primary ITP (n = 433) Secondary ITP* (n = 51)
Age, years, median (range) 52.2 (0.9, 98.5) 58.2 (0.4, 87.7)
Women, n (%) 238 (55.0) 32 (62.7)
Pregnancy, n (%) 15 (3.5) 2 (3.9)
Spain as a country of origin, n (%) 390 (90.1) 46 (90.2)
ITP diagnosis
Time since diagnosis, months, mean (SD)/range 0.7 (0.7) / 0.0 to 6.0 1.0 (0.7) / 0.0 to 2.6
Possible pseudothrombocytopenia, n (%) 9 (2.1) 0 (0)
Abnormal plasma coagulation, n (%) 24 (5.5) 7 (13.7)
Splenomegaly, n (%) 6 (1.4) 2 (3.9)
Family history of thrombocytopenia, n (%)
Yes 13 (3.0) 1 (2.0)
No 389 (89.8) 47 (92.2)
Unknown 31 (7.2) 3 (5.9)
Comorbidities, n (%)
Hypertension 102 (23.6) 10 (19.6)
Recent infections 62 (14.3) 7 (13.7)
Smoking 52 (12.0) 7 (13.7)
Cardiovascular disease 55 (12.7) 4 (7.8)
Diabetes mellitus 47 (10.9) 4 (7.8)
Gastrointestinal disease 30 (6.9) 4 (7.8)
Cancer 25 (5.8) 7 (13.7)
Thyroid disease 25 (5.8) 5 (9.8)
Alcoholism 11 (2.5) 0 (0)
Other substances abuse 2 (0.5) 0 (0)
Prior treatments, n (%) 71 (16.4) 7 (13.7)
Anti-inflammatory drugs 30 (6.9) 6 (9.8)
Antiplatelet drugs 27 (6.2) 1 (2.0)
Drugs possibly related to ITP 20 (4.6) 5 (9.8)
Vitamin K Antagonists 15 (3.5) 2 (3.9)
Other anticoagulants 5 (1.2) 2 (3.9)
Hematology tests, median (Q1, Q3)/(range)
Platelet count, 109/l 11.4 (4, 31)/(099) 12 (5, 49)/(199)
Hemoglobin, mmol/l 8.3 (7.5, 9.1)/(4.311.4) 7.9 (7.1, 8.8)/(3.811.5)
Leukocyte count, 109/l 7 (6, 9)/(226) 6 (5, 8)/(222)
*Systemic lupus erythematosus (9 cases); lymphoma (9); hepatitis C virus (HCV) (5); drug induced (3); Evans syndrome (3); pregnancy (2); human immuno-
deficiency virus (HIV) (2); collagenosis (2); antiphospholipid syndrome (2); hepatitis B virus (HBV) (1); HCV/HBV (1); liver cirrhosis (1); Herpes Zoster infection
(1); urinary tract infection (1); thyroid disease (1); hemolytic anemia (1); ulcerative colitis (1); celiac disease (1); Waldenstrms disease (1); not specified (4).

cocaine (1), cocaine/cannabis (1).

acetylsalicylic acid (1); amoxicillin (1); amoxicillin/clavulanate (2); antibiotic (1); carbamazepine/ibuprofen/enalapril (1); clopidogrel (1); deflazacort (1); val-
proic acid (1); diclofenac (1); doxazosin (1); doxycycline (1); etanercept (1); fosfomycin/metamizol (1); ibuprofen (1); irbesartan plus hydrochlorothiazide (1);
metamizol (1); simvastatin (1); simvastatin/fluoxetine/glimepiride (1); simvastatin/losartan plus hydrochlorothiazide (1).

Acetylsalicylic acid (1); amoxicillin (1); carnitine/arginine/quinine (1); chloroquine (1); meropenem/vancomycin/pentoxifylline (1).
Q1 = 25th percentile; Q3 = 75th percentile; SD = standard deviation.

(12.0%) and dexamethasone (6.2%) (Table 2). The dur- The response to first-line therapies was 92.1% (95%
ation of first-line corticosteroid treatment was >6 confidence interval 89.295.0%) (Figure 3). The median
weeks in 59.5% of patients. The median number of time to response was 22 days (Q1, Q3: 7, 78; range: 0
IVIg doses was 2 (Q1, Q3: 2, 5; range: 113). Romiplos- 560). Most of these responder patients (83%; 62% of
tim was given only in 0.2% of cases, whereas rituximab all primary ITP patients) maintained a platelet count
or other immunosuppressants were not used as first- 30 109/l at 12 months and did not require further
line therapies. treatment.

Table 2. Patterns of use of corticosteroids as first-line treatment for primary ITP.


Number (%) of primary ITP patients Treatment duration (days) Daily dose
(n = 433) Median (Q1,Q3) Mean (SD)
Corticosteroid/s as 1st line treatment 324 (74.8)
Corticosteroids monotherapy 176 (40.6)
Corticosteroids + IVIg ( other therapies) 142 (32.8)
Corticosteroids + other therapies (excl. IVIg) 6 (1.4)
Type of corticosteroid
Prednisone 282 (65.1) 77 (40, 136) Initial: 1.2 (0.4) mg/kg/67 (24) mg
Final: 0.7 (0.5) mg/kg/16 (32) mg
Metilprednisolone 52 (12.0) 6 (4, 27) 0.2 (0.3) g
Dexamethasone 27 (6.2) 4 (4, 8) 40 (0) mg
Deflazacort 5 (1.1) 112 (17, 123) 35.2 (21.8) mg
Prednisolone 2 (0.5) 17 (9, -) 2.3 (1.3) mg/kg
Q1 = 25th percentile; Q3 = 75th percentile; SD = standard deviation.
HEMATOLOGY 5

Figure 2. Utilization and outcome of diagnostic procedures other than platelet count undertaken in the study population to
confirm diagnosis of (a) primary (n = 433) and (b) secondary (n = 51) immune thrombocytopenia.

Only 17% of patients received second-line treat- Five percent and 2% of patients received third- and
ment. The median time between first-line and fourth-line treatment, respectively (mainly romiplostim,
second-line treatment was 1 day (Q1: 0, Q3: 73, rituximab and IVIg). The response rate in the third-line
range: 0339). The most frequent second-line treat- setting was 83.3%.
ments included rituximab (3.2%), corticosteroids
(3.0%), splenectomy (2.1%), romiplostim (1.8%), corti-
costeroids combined with IVIg (1.7%) and IVIg as Change over time in platelet counts and
monotherapy (1.6%), although a high variability was bleeding symptoms
observed. Other treatments (2.5%) included danazol, During follow-up, the median platelet count increased
azathioprine and eltrombopag. The response rate significantly in the overall cohort: 6 months: 119 109/l;
diminished slightly to 77.9% (Figure 3). (Q1: 66; Q3: 208; range: 0821); 12 months: 142 109/l
Overall, 3.5% of patients (n = 15) underwent sple- (Q1: 80; Q3: 221; range: 4876), without relevant differ-
nectomy during the 12 months of follow-up, and only ences between primary and secondary ITP patients. At
1 of them required further treatment. 12 months, approximately one quarter of patients
6 J. PALAU ET AL.

Figure 3. Therapeutic management of patients with primary ITP in Spain.

(26.3%) still had thrombocytopenia (<100 109/l). No Discussion


relevant changes were observed in hemoglobin levels
The present study constitutes the first national Spanish
or leukocyte count.
registry designed to provide updated information on
At 6 months, 12.7% of patients still had bleeding
ITP characteristics and management in the clinical
symptoms in the overall cohort. This percentage
practice. According to the available epidemiological
remained similar at 12 months (9.5%). The relative fre-
data on ITP, if the annual incidence is around 20 per
quency of each symptom was comparable: cutaneous
million [4,5], during the one and half year period of
bleeding: 9.1% at 6 months, and 5.7% at 12 months;
recruitment in the 70 participating centres (32% of
oral cavity bleeding: 4.0 and 3.0%; epistaxis: 3.4 and
the 220 hematology services in Spain) [29], with a 45
2.7%; muscle hematoma: 0.8 and 0.2%; gastrointestinal
million population, the number of incident ITP cases
bleeding: 0.6 and 1.0%; metrorrhagia: 1.3 and 1.2%;
during that period was around 1350, which implies
hematuria: 0 and 0.2%; intracranial hemorrhage: 0.4
that we managed to recruit more than one third of
and 0%; articular hematoma: 0 and 0%. Also the
all new ITP cases in Spain.
mean number of episodes (in patients with at least
The socio-demographic characteristics of our cohort
one episode) remained similar between the baseline
were quite similar to those described in prior studies
6 months and the 612 months periods (data not
from the United Kingdom (UK) [5], France [30],
shown).
Denmark [31], Japan [32], United States (US) [33], and

Table 3. Characteristics of the patients with primary ITP at diagnosis according to first-line treatment.
No treatment Corticosteroids monotherapy Corticosteroids + IVIg
(n = 82) (n = 176) (n = 142)
Age, years, mean (SD) 54.9 (23.6) 49.1 (25.4) 51.6 (25.3)
Women, % 47.8 63.3 46.2
Hematology tests, median (Q1, Q3)
Platelet count, 109/l 54 (32, 80) 12 (5, 24) 4 (2, 10)
Hemoglobin, g/dl 8.7 (8.0, 9.6) 8.3 (7.6, 9.0) 8.0 (7.1, 9.0)
Leukocyte count, 109/l 6 (5, 8) 7 (6, 9) 7 (6, 9)
Symptoms at diagnosis, %
Cutaneous bleeding 20.7 68.8 76.0
Oral cavity bleeding 6.5 27.6 49.0
Epistaxis 3.3 16.6 26.9
Muscle hematoma 1.1 6.0 7.7
Gastrointestinal bleeding 1.1 2.5 7.7
Metrorrhagia 0 6.0 5.8
Hematuria 0 0.5 4.8
Intracranial hemorrhage 0 0 5.8
Articular hematoma 0 0 0
Q1 = 25th percentile; Q3 = 75th percentile; SD = standard deviation.
HEMATOLOGY 7

in the Pediatric and Adult Registry on Chronic ITP [32,34]. The relative frequency of each symptom was
(PARC-ITP) Registry, which recruits patients from 31 comparable at the three time points, which suggests
countries worldwide (not Spain) [34]. It is important that response to treatment improves symptomatology
to note that these previous studies only included at all levels. Despite the improvement in platelet
primary ITP patients. In our study these patients counts, some events of potentially serious bleedings
accounted for 90% of the cohort, and their baseline (gastrointestinal bleeding, metrorrhagia, intracranial
characteristics were similar compared with those of haemorrhage) are still seen more than 6 months after
patients with secondary ITP. For example, the median diagnosis, which should make us aware of the fact
age was 52 years in our sample (58 years in patients that some patients are at increased risk and must be
with secondary ITP) and 56 years in the Japanese carefully followed up over time.
cohort [32] (most of the other studies included only In our cohort, 8 in 10 patients with primary ITP
adult patients), with a wide age range, and the percen- received a first-line treatment, which is slightly higher
tage of women was 56% (62%, secondary ITP cohort) than that reported in the PARC-ITP Registry (around 7
compared to 55% in UK [5], 60% in France [30], 61% in 10 adult patients) [34]. The relative distribution of
in Japan [32], and 62% in Denmark [31]. In the PARC- each treatment (mainly corticosteroids monotherapy,
ITP Registry the percentage of women is 68% in followed by corticosteroids plus IVIg) is also very
adults and 46% in children [34]. similar to that reported in the PARC-ITP [34]. This thera-
Given the nature of this registry-based study, we peutic approach was fairly homogeneous and, in
cannot rule out any misdiagnosis, as suggested by general, conformed to the recommendations of the
the presence of splenomegaly in 6 cases (1.4%) that consensus. As expected, patients with primary ITP
were labelled as primary ITP. Physicians in these cases who received corticosteroids plus IVIg had the lowest
probably considered that a slight increase in spleen platelet counts and worst bleeding symptoms at base-
size, as an isolated finding, was not enough to rule line, suggesting an adequate intensification of treat-
out primary ITP. A similar explanation can be argued ment in those patients at highest risk.
for the few cases with a family history of thrombocyto- Remarkably, the duration of corticosteroid treat-
penia, which were interpreted to be not related to ITP. ment was too high in the majority of patients with
The most common ITP associated disorders were primary ITP (almost two thirds received them for
systemic lupus erythematosus (1.8% of the overall more than 6 weeks). The response rate to the first-
population) and lymphoproliferative syndromes line treatment was very high and only 2 in 10 patients
(1.8%), followed by HCV/HBV/HIV infections (1.9% initiated a second-line treatment, much more diverse
overall). Drug-induced ITP was very rare (0.6%). In the and not standardized. At 12 months 74% of patients
study by Neylon et al. [5] drug-related ITP was as had normal platelet counts in absence of treatment,
high as 8%, and 9% of patients had a history of which suggests that the disease may become persist-
recent infection, compared to 14% in our sample. ent in around one quarter of patients, despite current
We observed a considerable number of diagnostic management practices.
procedures, which in general agreed with those rec- Our study has some limitations. As the study was
ommended by the recent consensus documents, observational, we could not establish a causal relation-
[25,26] although the study was performed before ship between the administered treatments and the
their publication. Those with the highest rate of posi- observed response rates, nor can we rule out the possi-
tive findings were Helicobacter pylori testing, antinuc- bility that these responses were associated with the
lear antibodies and HBV serology, observing highest natural evolution of disease. Strengths of our study
rates of positives among patients with secondary ITP. include its relatively large sample size and the
It must be noted the use of platelet-associated anti- unbiased, geographically distributed recruitment,
bodies testing in 21 and 41% of primary and secondary which ensures the representativeness of our sample.
ITP patients, respectively. This test, according to the last In conclusion, there is a wide variability in ITP
recommendations, has unproven or uncertain benefit patients. The onset of disease may occur at any age
in the differential diagnosis of ITP [25,26]. and gender and may or may not be associated to
Platelet counts at diagnosis were extremely low, prior infections such as Helicobacter pylori or HBV. In
with three quarters of patients below 30 109/l in the the Spanish setting, there is also a great variability in
primary ITP cohort. This observation is entirely compar- the application of diagnostic methods of ITP, which
able to that reported in prior studies (74% of patients sometimes do not fit the current recommendations.
below 30 109/l in Denmark [31]; median of 7.5 In patients with primary ITP the therapeutic approach
109/l in France [30]; mean of 22 109/l in Japan) [32]. of the first-line is fairly homogeneous and conforms
These low levels were associated with an important to the recommendations of the consensus, except for
number of patients with bleeding symptoms, whose an excessive duration of corticosteroids therapy.
type and incidence was also very similar to that Second-line treatments are much more diverse and
reported in previous newly diagnosed ITP populations not standardized. At one year, the disease persists in
8 J. PALAU ET AL.

around one quarter of patients, despite current thera- Gambarte; H. San Pedro de Alcntara, Dra. Nuria Bermejo;
pies available. These results reflect the need for improv- H. Sant Joan de Deu Martorell, Dra. Eva Snchez, Dr German
de las Heras; H. Sant Pau, Dr David Valcarcel, Dra. Salut
ing the therapeutic management of ITP patients in
Brunet, Dra. Adriana Sierra; H. Segovia, Dra. Carmen Olivier;
Spain through uniform implementation of inter- H. Severo Ochoa, Dr Pedro Snchez Godoy, Dra. Eva Yebra
national consensus recommendations. Fernndez; H. Son Lltzer, Dr Joan Bargay Lleonart;
H. Universitario de Canarias, Dra. M Jos Rodrguez Salazar;
H. Universitario Rafael Mndez de Lorca, Dr Ral Prez
Lpez; H. Universitario Santa Maria del Rosell de Cartagena,
Acknowledgments Dra. Jernima Ibez Garcia; H. Vall dHebron, Dra. Esther
Writing assistance was supported by Amgen and provided by Sancho, Dr Javier Bueno; H. Valle del Naln (Langreo), Dr
Dr Neus Valveny, from TFS Develop. The authors wish to Jose Manuel Alonso; H. Universitario Virgen de Valme, Dr
thank to all the Investigators of the TIMES Registry Study (in Eduardo Ros; H. Virgen de la Luz de Cuenca, Dr Jess
alphabetical order by hospital name): C. U. de Navarra, Dr Manuel Vall, Dra. Mara Josefa Busto Medina; H. Virgen de la
Jos A. Pramo; CHU A Corua, Dra. M Fernanda Lpez Fer- Salud, Dr Angel Remacha, Dra. Elena Gutirrez; H. Virgen del
nndez; Fundacin Jimnez Daz, Dra. Sol Snchez; Roco, Dra. Ftima de la Cruz.
H. Albacete, Dra. ngela Ibez, Dra. Mara Jos Var Castro;
H. Arnau de Vilanova, Dra. Esther Herrera de Pablo, Dra.
Carmen Benet, Dr Rafael Lluc; H. Arnau de Vilanova (Lleida), Disclosure statement
Dra. Rosa Isabel Upegui, Dr Maci; H. Carlos Haya, Dra. No potential conflict of interest was reported by the authors.
Mara Eva Mingot; H. Clnico de Salamanca, Dr Jos Ramn
Gonzlez Porras; H. Clnico de Santiago, Dra. Susana Prez
Crespo; H. Consorci Sanitari de Terrassa, Dra. Laura Vicente Funding
Folch; H. Consorci Sanitari de Terrassa, Dra. Marta Garcia
Pintos; H. Costa del Sol, Dra. Maria Esperanza Moreno; H. de This study was financially supported in part by a grant from
Cabuees, Dra. M Cristina Fernndez Canal; H. de Ciudad Amgen S.A.
Real, Dra. Carmen Calle; H. de Donostia, Dra. Nagore Argoitia;
H. de Elche, Dr Jose Antonio Molina, Dr Venancio Conesa;
H. de Joan XXIII, Dr Andres Llorente; H. de la Fe, Dr Javier ORCID
Palau; H. de la Plana, Dr Jose Sanchs; H. de Navarra, Dra. M
Mara Eva Mingot http://orcid.org/0000-0001-9083-855X
Luisa Antelo; H. de San Eloy, Dr Jose Julio Hernndez Hernn-
Eduardo Ros http://orcid.org/l0000-0002-4072-3911
dez; H. de Vic, Dr Lluis Rodrguez, Dra. Camino Salgado; H. de
Vinalop, Dr Sergio Martnez Caabate; H. del Mar, Dra. Blanca
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