The Importance of a Bone Marrow Biopsy to Distinguish Primary Immune Thrombocytopenia From Indolent Haematological Malignancies

Primary immune thrombocytopenia (ITP) is characterised by an immune-mediated destruction of platelets and impaired platelet production [1, 2].

The diagnosis is one of exclusion, and any disorder presenting with isolated thrombocytopenia can mimic ITP [3].

To identify and describe patients initially diagnosed with ITP and included in an on-going clinical trial, when further diagnostics revealed other underlying disorders as the aetiology to the low platelet counts.

Patients were identified from the on-going clinical trial ‘A randomised fase III study of the efficacy of rituximab in combination with dexamethasone vs dexamethasone in newly diagnosed patients with ITP’. All patients had given their written informed consent. The diagnosis of ITP was defined as isolated thrombocytopenia, normal bone marrow biopsy, no splenomegaly assessed by ultrasound, normal TSH-levels and exclusion of secondary immune-, viral- or drug-induced thrombocytopenia.

Patients who were enrolled in the study but subsequently diagnosed with other underlying disorders and excluded from the protocol are described in the following.

116 patients had been enrolled in the clinical study at the time of these analyses. 9 patients were subsequently diagnosed with other disorders and excluded from the study.

The median time from inclusion in the ITP-protocol to diagnosis of the underlying disorder was 11 days (range 3 – 486 days).

4 patients were diagnosed with other haematological disorders (debut symptoms, see figure 1).

• DLBCL – Presenting with low platelet counts and anaemia. Bone marrow biopsy and peripheral smear were normal. A CT scan showed bilateral renal tumours (lymphomas) and a biopsy revealed diffuse large B-cell lymphoma.

• MDS – Presenting with low platelet counts and anaemia. 6 days after inclusion, a bone marrow biopsy revealed a hypoplastic marrow with severe megakaryocytopenia.

• Low-grade lymphoma – presenting with low platelet counts. 11 days after inclusion, a bone marrow biopsy revealed small lymphocytic lymphoma. There were no abnormalities in the peripheral blood smear and no peripheral lymphocytosis. A CT scan showed multiple marginally enlarged lymph nodes.

• MDS/AML – Presenting with low platelet counts and mild iron deficiency anaemia. The bone marrow was hyperplastic with no apparent dysplastic abnormalities. After inclusion in the study, the patient had sustained platelet counts of 30–80 ×10⁹, mild anaemia and recurrent infections. Myelodysplastic syndrome was suspected based on clinical findings. A second bone marrow biopsy was performed 1 year after inclusion due to a decreased leukocyte count. The patient was diagnosed with acute myeloid leukaemia FAB-M2.

4 patients with CMV presented median platelet count of 6 ×10⁹/L (range 4–12 ×10⁹/L), petechiae (4 patients) and mucosal bleeding (3 patients). 1 patient had flu-like symptoms and elevated leucocyte count. CMV was diagnosed by positive IgM titer after a median of 17,5 days (range 7 –29).

1 patient was diagnosed with antiphospholipid syndrome 17 days after inclusion. Conclusion

The diagnosis of ITP is one of exclusion, and it is essential that patients presenting with isolated thrombocytopenia be thoroughly tested for underlying disorders. The present study has shown that a bone marrow biopsy may be a prerequisite and the only diagnostic tool to distinguish ITP from MDS or other low-grade malignancies. A bone marrow biopsy is recommended in all elderly patients in whom indolent haematological malignancies initially may mimick ITP.

Gudbrandsdottir:GlaxoSmithKline: Research Funding; Amgen: Research Funding. Frederiksen:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees.