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Blood, 1 February 2001, Vol. 97, No. 3, pp. 812-814
BRIEF REPORT
Helicobacter pylori eradication can induce platelet
recovery in idiopathic thrombocytopenic purpura
Giovanni Emilia,
Giuseppe Longo,
Mario Luppi,
Giovanna Gandini,
Monica Morselli,
Leonardo Ferrara,
Sergio Amarri,
Katia Cagossi, and
Giuseppe Torelli
From the Department of Medical Sciences, Section of
Internal Medicine and Hematology, and Department of Paediatrics,
University of Modena, Italy.
 |
Abstract |
Recent reports have suggested an association between
Helicobacter pylori infection and idiopathic
thrombocytopenic purpura (ITP). The prevalence of H pylori
infection and the effect of its eradication in a series of 30 ITP
patients were investigated. H pylori infection has been
documented in 13 patients (43.33%) by 13C urea breath test
and confirmed by histologic examination. Bacterium eradication with
antibiotics, obtained in 12 of 13 infected patients (92.3%), led to a
complete response in 4 (33.33%) and to a partial response (platelets
90 × 109/L-120 × 109/L) in 2 (16.66%).
The response was maintained for a median of 8.33 months, but 1 patient
relapsed 7 months after eradication. Search for H pylori
infection seems appropriate in ITP patients at diagnosis. Bacterium
eradication provides a new good option for a nonimmunosuppressive
treatment in some ITP patients.
(Blood. 2001;97:812-814)
© 2001 by The American Society of Hematology.
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Introduction |
Helicobacter pylori has been
clearly recognized as the main cause of gastritis and most cases of
peptic ulcer,1 and it has also been implicated in the
pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid
tissue lymphoma.2 It has been hypothesized that the host
immunologic response against H pylori plays a main role in
determining gastric mucosal injury, through the release of cytokines
and the action of autoantibodies against H+/K+-adenosine triphosphatase of gastric
epithelial cells.3,4 Moreover, there is increasing
evidence that H pylori strains are highly diverse and that
strain diversity associated with variability in host immune response
may contribute to the clinical outcome in infected
patients.5 In the last few years, H pylori has been implicated in the pathogenesis of some autoimmune diseases, such
as rheumatoid arthritis,6 autoimmune thyroid
diseases,7 and idiopathic thrombocytopenic purpura
(ITP).8 Relevant to this, Gasbarrini et al8
recently showed a high prevalence of H pylori infection in
patients with ITP and reported a good response to bacterium eradication
in most of them. This finding has been confirmed in a further anecdotal
ITP case.9 Thus, we performed a prospective open study to
verify the prevalence of H pylori infection and the effects
of its eradication in a larger proportion of patients with
chronic ITP.
| |
Study design |
Thirty patients with ITP were evaluated, including 13 males and
17 females; median age was 50.3 years (range 17-89). ITP was defined by
idiopathic thrombocytopenia (platelets < 100 × 109/L) when other causes had been excluded,
megakaryocytic hyperplasia in the bone marrow, shortened platelet
survival (measured using 111In-labeled platelets), and
increased autoantibodies against platelets (platelet-associated
immunoglobulin G [PAIgG]) in the serum.
H pylori infection was assessed by 13C urea
breath test (Helicobacter test, Infai, Bochum, Germany), by
the detection of serum antibodies (indirect immunofluorescence) and,
whenever possible, by histologic examination (Giemsa stain) of
specimens obtained by an upper gastrointestinal endoscopy.
The presence of serum antibodies against hepatitis C virus was also
evaluated by the enzyme-linked immunosorbent assay and confirmed by the
recombinant-based immunoblot assay. All immunosuppressive treatments
were withdrawn 1 month before eradication except in 1 patient.
H pylori eradication was performed with
amoxicillin (1000 mg twice daily), clarithromycin (250 mg 3 times
daily), and pantoprazole (40 mg twice daily) for 7 days. Eradication
was assessed by urea breath test 4 weeks after treatment withdrawal. Platelet counts were monitored every 2 weeks and assessed at 3 and 6 months, after the end of treatment. In statistical analysis, data were
expressed as the mean (SD) or median (range) as appropriate and
were analyzed by using the t test. Percentages were compared by  2 test (Fisher exact test for values  5). A
P value < .05 was considered statistically significant.
Approval for this study was obtained from the Institutional Review
Board of the University of Modena, and informed consent was provided
according to the Declaration of Helsinki.
| |
Results and discussion |
H pylori infection was found in 13 of 30 ITP
patients (43.3%) by 13C urea breath test. A prevalence of
infected males was noted (8 infected vs 5 uninfected; 5 infected
females vs 12 uninfected); median age was higher in infected patients
(63.2 [SD 14.6] vs 47 [SD 20.8] years, P < .02).
Platelet count was similar in infected and uninfected patients
(53.1 × 109/L [SD 28.5] vs 41.7 × 109/L
[SD 14.8], P < .16). Eight of 13 H
pylori-infected patients showed, at diagnosis, a severe
form of ITP (platelets < 30 × 109/L) and needed
immunosuppressive treatment (one also needed splenectomy) before
eradication. All patients showed a shortened platelet survival (2-4 days vs 8-9 days, as normal value), except for the patients no. 9 and
21 (Table 1). In 10 patients, the
diagnosis of H pylori infection was also confirmed by
histologic examination, while in 9 the presence of serum antibodies
against the bacterium was also detected. No patient was found to be
positive for serum antibodies against hepatitis C virus. The bacterium
eradication was obtained in 12 of 13 H pylori-positive
patients (92.3%). The follow-up, performed for a median of 8.33 months
(range 6-12), showed that 6 of the 12 eradicated patients (50%) had a
significant increase in platelet count after 3 and 6 months
(P < .007) (Table 1); 4 patients (33.3%) achieved a
complete response (CR) (P < .03), while 2 patients showed
a partial response (platelet count not higher than
120 × 109/L) (P < .16) (Figure
1A). The outcome over time of platelet
counts of H pylori-infected and treated patients
compared with noninfected patients looked similar (Figure 1B). Four
of 30 ITP patients were PAIgG-positive; 2 of these were infected with
H pylori. Among the responsive patients, 2 who achieved CR
were PAIgG-positive, while the remaining 4 were PAIgG-negative. The
only patient in whom H pylori eradication failed (no. 1) has
been unresponsive. Only 1 patient (no. 7), with a platelet count of
25 × 109/L, required steroid treatment for 1 month
after eradication; subsequently, the platelet count increased and
maintained in normal range without therapy. In 5 of the 6 responsive
patients followed for more than 6 months, the platelet count did not
change after H pylori eradication. In 1 patient (no. 10),
the ITP relapsed 7 months after eradication, although the breath test
remained negative.
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Table 1.
Clinical and laboratory characteristics in 30 idiopathic
thrombocytopenic purpura patients; H pylori eradication in
12
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| Figure 1.
The course of platelet counts over time.
(A) Platelet counts in 6 responsive patients. Each line represents
values from a single patient identified by number (Table 1).
 = H pylori eradication treatment (7 days). (B) Platelet
counts in all 30 ITP patients. Most uninfected patients are under
immunosuppressive therapy. Data are mean (SD). *P < .012
compared with initial count.
|
|
Our data lend further support to a relationship between
H pylori infection and ITP. The bacterium might induce, at
least in some cases, the formation of platelet autoantibodies by means of a chronic immunologic stimulus or a cross mimicry between platelets and itself.8,9 In respect to the only nonanecdotal report of the literature by Gasbarrini et al,8 we observed, in
our series of ITP patients, a lower prevalence of H pylori
infection (43.33% vs 61.11%, P < .37) and a lower
frequency of platelet response to the same eradication treatment
(46.14% vs 72.72%, P < .40). Moreover, only 33.33% of
our patients achieved a CR, versus 100% of eradicated patients in the
above-mentioned report (P < .27), even though eradication
has been obtained in a similar percentage of patients (92.3% vs
100%). We followed our patients for a median of 8.33 months versus a
maximum of 4 months in the study by Gasbarrini et al.8
This allowed us to document a relapse of ITP 7 months
after H pylori eradication in 1 PAIgG-negative patient.
Finally, variety in the frequency of H pylori-associated ITP and in the rate of platelet response to bacterium eradication may
be related either to the variability of host immune response to H
pylori or to the bacterium's high genetic diversity, ie, to the
existence of different H pylori strains with possibly
different pathogenic potential.5
In conclusion, even though the pathogenetic mechanisms of H
pylori-induced thrombocytopenia remain obscure, the search for H pylori infection and an attempt to eradicate bacterium in
positive cases seem appropriate in ITP patients at diagnosis. This
approach may be a new good option for a nonimmunosuppressive treatment, at least in some ITP patients. Further investigations on a larger number of patients, with a long follow-up, might allow a better definition of the true prevalence of H pylori infection and
the duration of the effect of its eradication in ITP patients.
| |
Footnotes |
Submitted February 17, 2000; accepted September 28, 2000.
Supported by Associazione Italiana per la Ricerca sul Cancro (AIRC),
Milan, Italy (M.L.) and Associazione Italiana contro le Leucemie (AIL),
section of Modena, Italy.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
Reprints: Giovanni Emilia, Department of Medical Sciences,
Section of Internal Medicine, Policlinico, via del Pozzo 71, 41100 Modena, Italy; e-mail: emilia.giovanni{at}unimo.it.
| |
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Top
Abstract
Introduction