Thrombotic Microangiopathy from Metastatic Signet Ring Cell Carcinoma
- AKI: Mechanisms - Case Reports
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
- Capistrano, Maria Christina Victoria M., Tufts Medical Center, Boston, Massachusetts, United States
Thrombotic microangiopathy (TMA) as a paraneoplastic syndrome is rare and outcomes can be devastating. We present a case of TMA as an initial presentation of metastatic signet ring cell carcinoma (SRCC).
Our patient is a 36-year-old female with a history of type 2 diabetes mellitus who presented with 3 weeks of dyspnea, cough and hemoptysis, then respiratory failure requiring intubation. Chest CT scan showed bilateral parenchymal mosaic attenuation. Her hemoglobin and platelets decreased to 7.8 g/dL and 68,000/µL, from 10.3 g/dL and 111,000/µL, respectively. Other work up include: MCV 82 fL, WBC 13,100/µL, LDH 18, 238 U/L, haptoglobin <10 mg/dL, Coomb’s negative, schistocytes on peripheral smear, fibrinogen 80 mg/dL, protime 14.7 seconds, INR 1.52, aPTT 40 seconds, potassium 8.4 mmol/L, creatinine 2.61 mg/dL, bicarbonate 9 mmol/L and lactate 19.1 mmol/L. She received FFP, PRBC and platelets. ADAMST13 was sent but plasmapheresis was initiated immediately. She was anuric and required CRRT. Despite the transfusions, her hemoglobin and platelets worsened at 5.3 mg/dL and 19,000//µL. She developed diffuse mottling and critical limb ischemia. After the 3rd hospital day, she was made comfort measures only. The autopsy showed metastatic poorly differentiated colon adenocarcinoma with signet-ring cell component, with diffuse bone marrow involvement.
The management of secondary TMA, such as DIC, pre-eclampsia, severe hypertension, are focused on the underlying cause. Metastatic carcinoma with bone marrow involvement can be an obscure differential and can prove fatal if undetected. The mechanism of how TMA occurs is not clear but there may be a role in mucin production from the signet ring cell subtype which causes endothelial cell dysfunction and thus causing thrombus formation. Bone marrow involvement generates abnormal angiogenesis that damages blood vessels and causes release of Ultra Large Von Willebrand Factor multimers, which has been implicated in the pathogenesis of MAHA. Metastatic malignancies have been misdiagnosed as TTP does not respond to plasmapheresis, had more respiratory symptoms and higher LDH. TMA as a paraneoplastic syndrome ultimately requires prompt chemotherapy and/or resection. Mucin producing tumors have been reported to present initially as TMA but by the time the diagnosis is made, it has widely metastasized and prognosis is notably poor.