Thrombotic Thrombocytopenic Purpura as a Marker for Disease Progression in a Patient with Metastatic Rectal Cancer.
Authors: Jordan Jody L. , Deveras Ruby Anne E. , Marshall John 
Published: October 2019

The pathophysiology of thrombotic thrombocytopenic purpura (TTP) relates the ADAMTS 13 protease deficiency as a result of an inhibitor in acquired TTP, such as secondary to malignancy.

Relapsing TTP is due to the inhibition or relative deficiency of von Willibrand factor (vWf)-cleaving protease activity preventing the breakdown of unusually large multimers of vWf, with resultant platelet adhesion to the subendothelium, platelet aggregation, and endothelial damage (Nabhan, 2003). We describe the manifestation of TTP as marker for rectal cancer disease recurrence and progression.

A 60 y/o black male with Dukes C2 rectal cancer was treated with surgical resection, local radiation and six months of adjuvant fluoruracil and leucovorin. Two years later, he presented with fatigue, shortness of breath and confusion. He had a hemoglobin of 7.0 g/dl, platelets of 20,000, 2+ schistocytes, and acute renal failure with a creatinine of 1.5 mg/dl. TTP was confirmed with decreased ADAMTS 13 protease activity <6%(nl 67–177%) and the presence of an ADAMTS 13 inhibitor of 0.5u (nl 0–0.4u). Plasmaphoresis and high dose steroids were initiated with very good response.

His evaluation revealed a carcinoembryonic antigen (CEA) of 11.4 μg/L (normal <3.0 μg/L) and CT scan showed a new solitary liver mass. After optimal response from plasmapheresis, the liver lesion was surgically resected and pathology confirmed metastatic rectal adenocarcinoma. His TTP improved and after resection his ADAMTS 13 inhibitor was <0.4 and ADAMTS activity had improved to 49%, but was not normal. This suggests that the resection was not curative. He was tapered off plasmaphoresis for several months. TTP relapse occurred, with ADAMTS inhibitor present at 0.9 IU and activity of <6%, prior to confirmation of numerous new hepatic lesions on CT scan.

Palliative chemotherapy with FOLFIRI (irenotecan, 5-FU, and leucovorin) achieved a partial remission of his rectal cancer. He also had a good therapeutic response for his relapsed TTP, with improved ADAMTS 13 activity to 27%, but continued to required weekly maintenance plasmapheresis prior to chemotherapy. Progression of his rectal cancer was preceded by relapsed TTP, requiring intensification of treatment with increased frequency of plasmapheresis. CT scan and rising CEA confirmed rectal cancer progression, and his chemotherapy was changed to XELOX (capecitabine and oxaliplatin). Response to chemotherapy correlated with stable disease with regards to his TTP.

Thrombotic thrombocytopenic purpura and the related hemolytic uremic syndrome (HUS) are rare, but well described complications in patients with adenocarcinomas, including gastrointestinal, pancreatic, breast and prostate primaries. TTP has also been described following treatment with certain chemotherapeutic agents, including cisplatin, gemcitabine, bleomycin and mitomycin C. Only one case has been reported in the literature of TTP relapse at the time of tumor progression, and this was a patient with breast cancer (Amer. J. Clin. Oncology23(1): 74-7, 2000). However, there is no report of recurrent TTP-HUS serving as a marker for solid tumor disease recurrence with correlative ADAMTS 13 protease activity and inhibitor. We conclude that effective treatment of the primary adenocarcinoma is crucial to the control of malignancy associated thrombotic thrombocytopenic purpura, and ADAMTS 13 inhibiter and activity levels are important clinical indicators of disease progression and response to treatment.