Thrombotic Thrombocytopenic Purpura Associated with Bone Marrow Metastasis and Secondary Myelofibrosis in Cancer

Abstract

To examine the relationship between cancer and development of thrombotic microangiopathy (TM), the medical records of patients with known TM were examined in one institution from January 1981 to December 2002. Nine out of 93 patients with the established diagnosis of TM had active cancer. All nine of those patients had thrombotic thrombocytopenic purpura (TTP). Among those patients, two patients received chemotherapy prior to the development of TTP. Six of the seven patients who received no chemotherapy had extensive bone marrow metastasis and secondary myelofibrosis. There were two patients each with breast cancer, lung cancer, and stomach cancer. Severe anemia and thrombocytopenia with leukoerythroblastosis were prominent clinical features in all six patients. Four patients had neurological (mental) changes and three developed fever, but none had significant renal dysfunction. Upon establishing the diagnosis of TTP, four patients were treated with exchange plasmapheresis (EP) and two patients were treated with chemotherapy because there were no neurological changes. Three patients achieved complete remission of TTP, one with EP alone and two with chemotherapy. The one patient who achieved remission with EP alone was later treated with chemotherapy and survived for 2 1/2 years. The other three patients treated with EP alone died within 2 months after the diagnosis of TTP. Since TTP occurred in association with bone marrow metastasis and myelofibrosis in six patients among seven chemotherapy-untreated cancer patients, this marrow change was considered to be the possible cause of the development of TTP. It is recommended that all cancer patients with unexplained anemia and thrombocytopenia be evaluated for the coexistence of bone marrow metastasis and TTP.

Cancer Awareness in Atypical Thrombotic Microangiopathies

“…In pulmonary tumor TMA, a rare entity causing severe pulmonary hypertension in patients with disseminated malignancies [28,29], it was suggested that tissue factor and vascular endothelial growth factor, by inducing fibrin deposits and vascular hyperplasia, respectively, may be involved in the occlusion or stenosis of the pulmonary vasculature [30,31]. Additionally, malignant cells may produce substances favoring TMA, such as mucins [8]. By favoring vasoconstriction and endothelial cell apoptosis, tumor necrosis factor-␣ may have a role in the occurrence of TMA in patients with cancer [32].…”

Thrombotic Thrombocytopenic Purpura Secondary to an Occult Adenocarcinoma

“…TTP is generally idiopathic, and the association with adenocarcinomas is extremely infrequent [1,2].We report a case of a 69-year-old woman with TTP syndrome secondary to metastatic cancer and normal ADAMTS13 (von Willebrand factor [vWf]-cleaving protease) activity and propose the pathogenetic events underlying this unusual association.The patient was admitted to our hospital because of anemia (hemoglobin level 7.8 g/dl, mean cell volume 90 fl, reticulocyte count was 12%) and thrombocytopenia (platelet count 124 × 10 3 /mm 3 ). Other laboratory findings were: serum aptoglobin <8 mg/dl, lactate dehydrogenase 1,733 UI/l, and alkaline phosphatase 603 UI/l.…”

“…However, these and other investigations (gastroscopy, mammography, and bronchoscopy) could not document any primary neoplastic lesion. A diagnosis of TTP secondary to occult adenocarcinoma diffusely metastatic to bone marrow was established, but a few days later the patient died.Only a few cases of TTP secondary to metastatic adenocarcinoma are known in the literature [2][3][4][5][6][7]. The mechanism of secondary TTP is different from the idiopathic mechanism.…”

“…TTP is generally idiopathic, and the association with adenocarcinomas is extremely infrequent [1,2].…”

“…Only a few cases of TTP secondary to metastatic adenocarcinoma are known in the literature [2][3][4][5][6][7]. The mechanism of secondary TTP is different from the idiopathic mechanism.…”