Sabrina Browning1, Burak Bahar2,3, Alfred Ian Lee1, Elan Gorshein1. 1. Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. 2. Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA. 3. Department of Pathology and Laboratory Medicine, George Washington University, Children's National Hospital, Washington DC, USA.
Abstract
OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy that can have high mortality rates without prompt treatment. Standard treatment is urgent plasma exchange (PLEX), which leads to disease remission in the vast majority of patients. Deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) alone is not sufficient to cause the clinical manifestations characteristic of TTP. We present a case of acquired TTP, where spontaneous recovery was observed prior to initiation of any TTP-specific therapy. CLINICAL PRESENTATION: A 73-year-old asymptomatic female presented with new-onset mild haemolytic anaemia and thrombocytopenia. Further testing revealed a significantly reduced ADAMTS13 activity level and an ADAMTS13 inhibitor, concerning for acquired TTP. On reassessment, the patient's haematologic parameters had been corrected prior to initiation of therapy. During subsequent follow-up three months later, she developed acute worsening thrombocytopenia indicative of relapsed, acute TTP. The patient was then successfully managed with PLEX and rituximab and achieved a sustained remission. DISCUSSION AND CONCLUSION: TTP is a haematologic emergency that requires urgent therapy to reduce morbidity and mortality. However, it is well documented that individuals with hereditary TTP and a proportion with acquired TTP in clinical remission can have low or nearly absent ADAMTS13 activity levels without evidence of microangiopathic haemolytic anaemia (MAHA) or thrombotic manifestations. Our patient represents a unique case of confirmed ADAMTS13 deficiency due to a documented inhibitor, leading to mild haemolytic anaemia and thrombocytopenia both of which recovered spontaneously. We propose that this scenario could represent a 'subclinical' TTP state that precedes the development of clinically significant disease.
OBJECTIVES:Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy that can have high mortality rates without prompt treatment. Standard treatment is urgent plasma exchange (PLEX), which leads to disease remission in the vast majority of patients. Deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) alone is not sufficient to cause the clinical manifestations characteristic of TTP. We present a case of acquired TTP, where spontaneous recovery was observed prior to initiation of any TTP-specific therapy. CLINICAL PRESENTATION: A 73-year-old asymptomatic female presented with new-onset mild haemolytic anaemia and thrombocytopenia. Further testing revealed a significantly reduced ADAMTS13 activity level and an ADAMTS13 inhibitor, concerning for acquired TTP. On reassessment, the patient's haematologic parameters had been corrected prior to initiation of therapy. During subsequent follow-up three months later, she developed acute worsening thrombocytopenia indicative of relapsed, acute TTP. The patient was then successfully managed with PLEX and rituximab and achieved a sustained remission. DISCUSSION AND CONCLUSION: TTP is a haematologic emergency that requires urgent therapy to reduce morbidity and mortality. However, it is well documented that individuals with hereditary TTP and a proportion with acquired TTP in clinical remission can have low or nearly absent ADAMTS13 activity levels without evidence of microangiopathic haemolytic anaemia (MAHA) or thrombotic manifestations. Our patient represents a unique case of confirmed ADAMTS13deficiency due to a documented inhibitor, leading to mild haemolytic anaemia and thrombocytopenia both of which recovered spontaneously. We propose that this scenario could represent a 'subclinical' TTP state that precedes the development of clinically significant disease.