Rituximab‐induced haemorrhagic thrombocytopenia in a patient with hairy cell leukaemia

A 44-year-old man developed severe, symptomatic thrombocytopenia with markedly raised d-dimer levels when treated with rituximab for hairy cell leukaemia (HCL). He presented with an abscess in the right erector spinae muscle. The full blood count on admission showed the following: haemoglobin concentration 9Æ4 g/dl, white cell count 1Æ4 · 10/l, neutrophil count 0Æ51 · 10/l, monocyte count 0Æ12 · 10/l and platelet count 44 · 10/l. The bone marrow cellularity was moderately increased with an interstitial infiltrate of small to medium sized lymphocytes with plentiful pale cytoplasm. The megakaryocytes were reduced but morphologically normal. The lymphoid infiltrate consisted of CD20-positive B cells, which were also positive for CD103, CD11c and CD25, confirming a diagnosis of HCL. He was treated with intravenous antibiotics for a Staphylococcus aureus isolated from the abscess, and granulocyte colony-stimulating factor (G-CSF). There was marked clinical improvement, but a repeat computerised tomography scan after 2 weeks showed only slight improvement (4 · 4 cm). As his neutropenia persisted despite G-CSF, he was treated with rituximab. This was considered a less myelosuppressive and safer treatment than purine analogues in the setting of a deep-seated abscess. Four hours after the administration of the monoclonal antibody, the patient experienced severe knee pain but did not demonstrate fever, chills, palpitation or other features of a ‘cytokine-release syndrome’. Simultaneously, he developed blood blisters in the mouth, petechiae on his legs and gastrointestinal bleeding. The platelet count before the start of the infusion was 31 · 10/l but fell to 6 · 10/l when checked an hour after the development of symptoms. The coagulation results showed a prothrombin ratio of 1Æ2, activated partial thromboplastin time ratio of 1Æ2, fibrinogen of 4Æ1 g/l and a d-dimer of 33 020 ng/ ml. Two adult doses of platelets were administered and an urgent oesophago-duodenoscopy (OGD) was arranged. Bleeding resolved within a day and the OGD was normal. The platelet count rose to 31 · 10/l on the following day and remained between 30 and 40 · 10/l unsupported with platelet transfusions. The mucosal lesions resolved within a couple of days. The d-dimers also fell to 13 080 ng/ml at 24 h and normalised within 6 d. He was started on interferon with a view to improving his neutropenia prior to definitive treatment with cladribine once the neutropenia and abscess had resolved. Rituximab is active in the treatment of HCL although its use is restricted mainly to those who have not responded to purine analogues (Hagberg & Lundholm, 2001). Common side effects include infusion reactions, and cytokine-release syndrome. Thrombocytopenia is extremely rare. There has been a single case report of a patient with HCL developing severe thrombocytopenia with rituximab infusion a day after the development of cytokine-release syndrome (Otrock et al, 2005). Our patient did not have any features of the cytokinerelease syndrome and the timing of severe thrombocytopenia was immediately after the infusion. The very high d-dimer level suggests intravascular fibrinolysis. The accompanying drop in the platelet count and possibly low fibrinogen in the clinical context suggested disseminated intravascular coagulation as the causative process. Infection and malignancy may cause a rise in d-dimers but the time course of events makes these explanations most unlikely. Platelet binding of a soluble anti-CD20/rituximab complex has also been postulated. Rigamonti et al (2001) described bleeding with severe thrombocytopenia in a lymphoma patient with massive splenomegaly. Other case reports of the association have not described clinically important haemorrhage (Leo et al, 2004; Shah & Grethlein, 2004; Pamuk et al, 2005). Rituximab should be used with caution in patients who have significant bone marrow involvement with B-cell malignancies and moderate to severe thrombocytopenia.