Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura

Authors


Miguel A. Sanz, Servicio de Hematología, Hospital Universitario la Fe, Av. Campanar, 21, 46009 Valencia, Spain. E-mail: msanz@uv.es

Abstract

Eradication of Helicobacter pylori infection has been associated with the correction of thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP). We have analysed the response to eradication of H. pylori in a series of 56 adult patients with chronic ITP. Forty patients had H. pylori infection (71%) that was eradicated in 23 of 32 evaluable patients (72%). Platelet counts did not significantly vary according to H. pylori treatment outcome. Three of 56 patients (5%) achieved a partial response attributable to H. pylori eradication. Therefore, detection of H. pylori infection should not be routinely included in the initial work-up of ITP.

In recent years, several studies have investigated the relationship between Helicobacter pylori infection and a variety of extragastric disorders, including autoimmune diseases. A small series study (Gasbarrini et al, 1998) suggested that patients with autoimmune thrombocytopenia could increase their platelet counts after eradication of H. pylori infection. This interesting phenomenon has also been described in individual case reports (García et al, 1999; Grimaz et al, 1999). Recently, a study by Emilia et al (2001), based on a larger series, reported an overall response of 50% after H. pylori eradication. All these results support the hypothesis that, among idiopathic thrombocytopenic purpura (ITP) patients, an H. pylori-associated variant can be identified and then treated without immunosuppressive therapy. We report here the results of a prospective study that failed to demonstrate a significant improvement in platelet counts after eradication of H. pylori infection in a series of 56 patients diagnosed with chronic ITP.

Patients and methods

Patients Adult patients with a diagnosis of chronic ITP according to the American Society of Hematology guidelines (George et al, 1996) were evaluated prospectively. Inclusion criteria were absence of treatment within the previous 3 months and a platelet count < 100 × 109/l. Patients considered at bleeding risk who would require active treatment (rapidly decreasing platelet count, actual haemorrhage or programmed invasive procedures) were excluded. Informed consent was achieved before entry into the study.

Diagnosis The [13C]-urea breath test (Logan et al, 1991) was used for diagnosis of H. pylori infection.

Treatment Patients with H. pylori infection were given oral treatment using the OCA combination (omeprazole 20 mg twice daily, claritromycin 500 mg twice daily and amoxycillin 1 g twice daily), for 7–10 d.

Assessment of response Eradication or persistence of H. pylori was assessed after a minimum of 2 months using the [13C]-urea breath test. Platelet count response to OCA combination was assessed at 3 months after eradication treatment. Complete response was defined as the achievement of a platelet count ≥ 150 × 109/l. Partial response was defined as the achievement of a platelet count of 50–149 × 109/l or an increase > 30 × 109/l with respect to the baseline value (Vianelli et al, 2001). The chi-square test or Fisher's exact test, when appropriate, was used to compare proportions, and the Student's t-test or Mann–Whitney rank sum test, when appropriate, was used for comparison of means.

Results

Clinical and laboratory data

Between November 1998 and November 1999, 56 patients (38 women, 18 men), with ages ranging from 17 to 80 years (median 54) were entered in the study. Median time from diagnosis was 32 months (range 2–250). Thirty-nine patients (70%) had never been treated. Six patients had been given only first-line therapy with prednisone, and the remaining 11 patients had required additional second-line therapy, including splenectomy in four cases. Forty patients (71%) were positive for H. pylori and received eradication treatment. Eight patients (20%) were not assessable for response (four lost to follow-up, two undetermined H. pylori status, one intolerant to OCA combination, one spontaneous recovery before starting eradication treatment). Eradication of H. pylori was achieved in 23 out of 32 assessable patients (72%).

Platelet response

Changes in platelet counts according to the eradication or persistence of H. pylori infection in infected individuals as well as in non-infected patients (control group) are summarized in Table I. Of note, only partial responses were documented. The response rate was not significantly different between non-infected and infected ITP patients, regardless of H. pylori eradication. Duration of response in two of the three patients in whom eradication was achieved was 18 and 21 months respectively. The remaining patient is in continuous remission at 24+ months.

Table I.  Platelet counts (means ± SD) according to H. pylori status and response to eradicating treatment.
 WithoutWith infection (n = 32)

Platelet count ( × 109/l)
infection
(n = 16)
Eradication
(n = 23)
Persistence
(n = 9)
Basal58 ± 2357 ± 2262 ± 31
At 3 months67 ± 2863 ± 2770 ± 44
Increment (> 30 × 109/l)3 (19%)3 (13%)1 (11%)

Discussion

In this series, there were no significant differences in the evolution of chronic ITP patients depending on the H. pylori status and on the response to the eradication treatment. We observed a higher prevalence of H. pylori infection and a lower platelet response to the eradication treatment than those previously reported (Gasbarrini et al, 1998; Emilia et al, 2001) (Table II). From an intent-to-treat point of view, only three of 56 patients in our series (5%) received any benefit from this approach. In spite of its indubitable pathogenic interest, the clinical relevance of the above-mentioned phenomenon is low. In our opinion, there is insufficient evidence to include a search for H. pylori in the initial work-up of ITP patients.

Table II.  Comparative results of reported series.
 Gasbarrini
et al (1998)

n (%)
Emilia
et al (2001)

n (%)
Present
series
n (%)
Patients183056
H. pylori infection11 (61)13 (43)40 (71)
Assessable patients111332
Eradicated patients8 (73)12 (92)23 (72)
Platelet responders8 (100)6 (50)3 (13)
Responders/Treated8 (73)6 (46)3 (9)
Responders by intention
to treat
44%20%5%

Ancillary