Breast Cancer-Associated Thrombotic Microangiopathy

Abstract

Background: Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal condition, seems an entity distinct from classical thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Patients and Methods: All patients with breast cancer-associated TMA treated at our institution between 2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological mechanisms, we measured the serum activity of the metalloprotease ADAMTS13. Results: 8 patients were identified. All showed bone marrow infiltration of breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia. ADAMTS13 activity was mildly decreased in 4/6 patients (20–108%, normal range 30–120%), but none showed severely low levels as is characteristic of classical TTP. 6 patients were treated with anthracycline-containing fractionated chemotherapy, 5/6 patients experienced partial response. Overall survival was 13 months. Fractionated chemotherapy was well tolerated. Conclusions: Cancer-associated TMA has an underlying mechanism different from classical TTP. While bone marrow infiltration might be of major relevance, ADAMTS13 deficiency seems to be an epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and comparatively long survival.

Pathophysiology of tumour-induced microangiopathic haemolytic anaemia

“…CA-MAHA in our patient was reversed after chemotherapy initiation and she continues to do well more than 1 year since her presentation, suggesting that early diagnosis and treatment initiation are critical to improve patient outcomes. Despite similar clinical presentations, treatments for TTP (fresh frozen plasma, plasmapheresis) are not effective for CA-MAHA 2. Chemotherapy initiation with transfusion support during the acute presentation currently offers the only option for successfully treating the MAHA and prolonging survival 4 5…”

“…It is most frequently reported in patients with advanced stage cancers including breast, prostate, stomach and lung. CA-MAHA must be distinguished from other microangiopathic haemolytic anaemias including TTP, HUS and/or DIC, as therapies directed against these syndromes are ineffective in management of CA-MAHA 1 2. We describe a case of CA-MAHA in a patient with metastatic breast cancer (MBC), including successful treatment and correlative studies evaluating circulating tumour cells (CTCs) and microparticles (MPs), which may help in elucidating the pathophysiology behind CA-MAHA.…”

ADAMTS‐13 and von Willebrand factor predict venous thromboembolism in patients with cancer

“…A severely deficient ADAMTS‐13 activity (less than 10 IU mL −1 ) is observed in most patients with thrombotic thrombocytopenic purpura, a thrombotic microangiopathy characterized by VWF‐mediated platelet thrombi disseminated in the microcirculation, which is responsible for end‐organ ischemia . Thrombotic microangiopathy can also occur in association with cancer, with a pathophysiological mechanism involving ADAMTS‐13 deficiency ; the thrombotic microangiopathy is induced by the chemotherapy or the cancer itself . Interestingly, previous studies specifically investigating ADAMTS‐13 in cancer suggest that ADAMTS‐13 activity levels are decreased in patients with cancer when compared with patients without cancer ; they are also decreased in patients with disseminated compared with localized cancers .…”

Successful Remission of Hemolytic-Uremic Syndrome during the Third-line Weekly Gemcitabine for Metastatic Breast Cancer

“…If the HUS was from the tumor thrombotic microangiopathy from cancer progression,10 discontinuation of gemcitabine would not help in this setting.…”