A 61-year-old African American male with no significant past medical history presented to our institution's emergency department complaining of six-month history of progressively worse abdominal pain associated with anorexia and unintended weight loss. Computerized tomography (CT) scan of abdomen showed mild ascites and right pleural effusion; a subsequent CT of the chest revealed a large right pleural effusion with multiple subcentimeter (less than 4 millimeters) pulmonary nodules in the right upper and lower lobes. Initial laboratory workup revealed a complete blood count (CBC) with normochromic normocytic anemia (hemoglobin 7.3 g/dL), thrombocytopenia (platelets 36,000), and reticulocytosis (10%). Lactate dehydrogenase (LDH) was found elevated with a low haptoglobin. Coombs test was negative, and renal and liver functions were within normal limits. A peripheral blood smear confirmed CBC findings and showed schistocytes and microspherocytes. Given the likely diagnosis of thrombotic thrombocytopenic purpura (TTP), ADAMTS 13 activity was ordered and reported as 14% (low), which led to the initial confirmation of this disorder. The patient was started on high-dose steroids, plasmapheresis (PE), and fresh frozen plasma (FFP). After seven days of treatment, his platelet count increased to 428,000 and LDH decreased to 839. Extensive workup for secondary causes of TTP including malignancy was negative. Human immunodeficiency virus and hepatitis serologies were nonreactive. Pleural fluid analysis of right pleural effusion was consistent with an exudate; however, cytology and flow cytometry were negative for malignant cells. Quantiferon for tuberculosis was positive but acid fast bacilli stains and viral, fungal, mycobacterial, and bacterial cultures were negative. The possibility of latent tuberculosis was raised, and the patient was started on isoniazid. Once the patient was stable, video-assisted thoracoscopic surgery (VATS) with multiple pleural biopsies was done; however, no lesions were seen during the procedure, and pathology did not reveal any evidence of malignancy. Plasmapheresis and FFP were discontinued, steroids were tapered off, and eventually the patient was discharged with outpatient followup.
After 9 days, the patient returned to the emergency department complaining of worsening of abdominal pain and altered mental statues with dysarthria and bradypsychia. Once again, he was found thrombocytopenic (<10,000) and his LDH was very high (4000). CT brain showed no hemorrhage and electroencephalogram (EEG) revealed encephalopathy but no epileptogenic foci were found. The patient was admitted to medical intensive care unit, and PE and FFP infusions were started after a new peripheral blood smear led to confirmation of relapsed TTP. Subsequent magnetic resonance imaging (MRI) of the brain did not show any abnormalities. The patient eventually recovered with instaurated treatment, and he was discharged again with oral steroids. ADAMTS 13 activity at the time of discharge was 19%. However, after only 6 days, he was admitted again complaining of the same symptoms of abdominal pain and altered mental status. He was also found febrile, oliguric, and azotemic. Relapsed TTP was once again diagnosed, and ADAMTS13 activity was reported to be less than 10%. During his hospital stay he had two episodes of seizures and for that reason he was started on levetiracetam. EEG showed diffuse encephalopathy. Following seven days of treatment with PE and FFP, the patient had a significant overall improvement, and, after no hemolysis was found, the patient was transitioned to daily FFP infusions. Despite this, ADAMTS activity remained low, and, once FFP infusions were discontinued, his TTP relapsed again. After reinitiating treatment, rituximab 375 mg/m2 was started as second-line therapy.
After seven days of immunotherapy along with PR and FFP, ADAMTS13 remained persistently low (10%). Chemotherapy with CVP (cyclophosphamide, vincristine, and prednisone) was added for empiric treatment of potential low-grade lymphoma, with no significant response after two cycles of immunochemotherapy. He started complaining again of intense abdominal pain leading to acute abdomen that prompted an exploratory laparotomy. Surgical exploration revealed diffuse carcinomatosis with a tumor located on the left pelvis that was encasing the distal sigmoid colon. Pathology reported mesothelioma with malignant cells positive by immunohistochemistry to calretinin and D240, and negative for CEA and MOC31 (Figures 1, 2, 3, 4, and 5). Due to the extension of his disease, it was considered nonresectable. Based on his poor response to TTP treatment and concomitant primary malignancy, the diagnosis of paraneoplastic TTP-like syndrome (TTP-LS) was made. The patient continued with FFP while recovering from surgery, and then he was started on palliative chemotherapy with cisplatin plus pemetrexed, the best chemotherapy available for mesothelioma, aiming to control both his TTP-LS and malignancy. After four weeks of treatment, there were no signs of improvement and he was transferred to hospice to receive best supportive care.