Abstract
Introduction Thrombotic Thrombocytopenic Purpura (TTP) is a cause of microangiopathic-haemolytic anaemia and thrombocytopenia, associated with renal and neurological dysfunction with thrombotic complications causing significant morbidity and mortality.
Methods A restrospective single-institution analysis of patients with TTP treated between 1990–2005. Renal or bone marrow transplantation patients were excluded.
Results Forty patients were identified. Aetiology was idiopathic 75% (n=30), connective tissue disease-related 12.5% (n=5), malignancy-related 5% (n=2) and pregnancy-related 7.5% (n=3). Presenting features: neurological 62.5% (n=25), renal impairment (creatinine>0.11 mmol/L) 76% (n=28), microangiopathic-haemolytic anaemia 97.5% (n=39) and thrombocytopenia 100% (mean platelet-count 42x10^9/L). Mean Hb 93 g/L and mean Lactose dehydrogenase (LD) 2517 U/L (<420). 38 patients received up-front single plasma-volume plasma-exchange using fresh-frozen plasma (median 11 exchanges). All received steroids. Complete-response (CR) (normalisation of platelet count, LD, neurological examination and rising Hb), was achieved in 79% (n=30) following plasma-exchange of whom 43% (n=13) relapsed (median 14.5 days from therapy-cessation): eleven achieved CR2 with further therapy and two died from TTP-related complications. Partial-response (PR) was obtained in 7.9% (n=3) with up-front plasma-exchange: one remained in PR with prostate-cancer treatment and two relapsed: one achieved CR and one sustained-PR with further therapy. 13% (n=5) were refractory to plasma-exchange: four died from TTP-related complications and one achieved CR with treatment intensification. Therapeutic intensification included steroids (n=34), vincristine (n=7), intravenous immunoglobulin (n=6), Rituximab (n=3) and splenectomy (n=6).
Conclusion TTP is associated with a significant relapse-rate (43%) and TTP-related mortality (16%) despite plasma-exchange. Delineation of patients at high risk of relapse following CR will potentially allow targetted treatment intensification. Treatment intensification is also clearly required for patients with refractory TTP and consideration may be given to other immunosuppressive agents, such the chimeric monoclonal anti-CD20 antibody, Rituximab, as a steroid-sparing agent and to potentially avoid splenectomy. We propose a central TTP registry is developed within Australia such that therapeutic strategies can be systematically evaluated in a multicentre setting.
Microangiopathic haemolytic anaemia and thrombocytopenia due to combined vitamin B12 and folate deficiency masquerading as thrombotic thrombocytopenic purpura
