ITP is a common condition, with an estimated incidence of between 1:1000 and 1:10 000. It is more common in females than males by a ratio of 2–3:1.1
It may present with purpura, petechiae and can cause complications such as potentially fatal internal bleeding (gastrointestinal, intracerebral). Mortality for ITP is estimated at 4% overall, due largely to those with severe refractory thrombocytopenia.1
Outcomes for most patients with ITP are generally good, however.
ITP is a diagnosis of exclusion, as other causes are more common and often more readily reversible. Non-immune causes of thrombocytopenia, including hypersplenism, myelodysplasia, sepsis, viral infection, acute leukaemia and drug-induced bone marrow suppression, should first be considered. Immune thrombocytopenia can be divided into primary (idiopathic) and secondary causes ().
Blood films generally show an isolated thrombocytopenia with an increased mean platelet volume. Between 15% and 25% of ITP cases show an expression of antinuclear and antiphospholipid antibodies. Clotting screen and thyroid function tests are generally normal. Specific tests for ITP are still in development.
A stepwise approach is generally adopted in the management of ITP.
- Observation with treatment of underlying cause
- Corticosteroids, immunoglobulin G and anti-D
Roughly 10% of patients with ITP have remission, if left untreated.2
Standard practice is to commence treatment with steroid with or without immunoglobulin and with immunoglobulin when platelet count falls below 20 × 109
/l or below 50 × 109
/l in the presence of bleeding.3
Most strategies other than observation have significant side-effect profiles.
Risks of steroid treatment are manifold, and furthermore, chronic steroid use often fails in ITP treatment. The use of intravenous immunoglobulins is also not without risk.
Traditionally, if steroids and immunoglobulins fail, splenectomy was the third line with associated risks of infection and perioperative complications, including up to a 1% mortality.4
Rituximab (anti-CD-20 monoclonal antibody) has been associated with an improvement in platelet count response in 60% of patients but is associated with virus reactivation and acute toxicity.5
In postsplenectomy refractory thrombocytopenia, numerous agents have been utilised, including immunosuppressants (cyclophosphamide, mycophenolate mofetil, azathioprine and ciclosporin) and androgenic treatment (Danazol). There is no substantial evidence for the use of any single agent. Each has its own inherent risks.
By contrast, treatment of H pylori-
induced ITP is more favourable in terms of side effects,
with some promising clinical response to eradication therapy.6
is a commensal Gram-negative bacterium that colonises the human stomach in more than 50% of the world's population. It is associated with chronic gastritis, peptic ulcer disease and gastrointestinal neoplasia. H pylori
infection is increasingly being implicated in diseases beyond the gastrointestinal tract, including the cardiovascular and neurological systems.7
Research suggests, in line with most chronic infections, that there is a complex interaction between host and pathogen, and that particular genetic polymorphisms of both will predispose to certain disease manifestations. For instance, the balance between Th1 and Th2 responses in gastric mucosa contributes to severity of gastritis, and the persistence of H pylori
colonisation can be diagnosed with non-invasive methods, namely 13
C-urea breath test and antigen detection in faeces (sensitivity and specificity 90–95% in both cases).8 H pylori
stool antigen testing offers excellent specificity and sensitivity compared with invasive methods, and is a more accurate indicator of active disease than serology.9
The mechanism of how H pylori
causes ITP is incompletely understood, but may involve antibody molecular mimicry and platelet aggregation.10 11
The virulence factors expressed by different strains of H pylori
may contribute to this process with bacteria expressing the cytokine-associated gene A (CagA
) implicated in cross-reactivity with platelet membranes. Recent work by Yeh et al12
postulate that in addition to causing platelet aggregation, specific H pylori
strains may cause platelet apoptosis via the P-selectin receptor on platelet cell surfaces, further reducing platelet counts.
Treatment options invariably include a proton pump inhibitor and a combination of antibiotics for 2 weeks. Eradication therapy is successful in 80–85% of patients.13
Overall, the literature concerning this area is inconclusive, with response rates of platelet counts following eradication therapy for H pylori
varying widely between studies. In certain countries, where the prevalence of H pylori
is higher, the response to eradication therapy is more pronounced in terms of platelet response.6
In Japan, the endemic strain of H pylori
tends to have higher CagA
expression rates. This may explain the increased response rate to eradication therapy.
Haematologists are increasingly including testing for H pylori as part of their ITP investigation. Further studies are being conducted into the association between H pylori-associated ITP and the effect of eradication.
- H pylori infection incidence increases with age, and associated increase in mortality.
- H pylori (CagA-producing strains) appear to be able to cause ITP in some individuals via an incompletely understood mechanism.
- There are sensitive and specific tests for H pylori, and it is treatable.
- ITP is a diagnosis of exclusion that carries a small but well-recognised mortality risk. Treatment options for ITP carry unfavourable side-effect profiles.
- Eradication therapy for H pylori is well tolerated, relatively inexpensive and provides an avenue for avoiding unnecessary medical and surgical intervention in patients who respond well, particularly older patients.