Case Presentation: A 66-year-old female with medical history of breast cancer s/p mastectomy and chemoradiation with no proven recurrence and a recent CT guided biopsy of paraaortic nodes showing adenocarcinoma of unknown primary who presented to the ED with chief complaint of shortness of breath and leg swelling. Physical examination was significant for BP of 169/106 and features of volume overload. Labs showed Hgb of 7.8, platelets of 76, PT/INR 1.1/27.3, Na128, potassium 4.0, bicarb 20, anion gap 12, BUN 48, creatinine 5.6, AST 85, ALT 18, T.bili 1.2. Labs were normal at baseline. CT abdomen showed enhancement of the bilateral kidneys and few lesions in the right lower lobe suspicious for infarcts. The patient was admitted to the ICU. In light of the initial presentation with hypertensive emergency, low platelets and hemoglobin and previous diagnosis of adenocarcinoma differentials of malignant hypertension, aHUS and possible TTP were considered. ADAMTS 13, LDH, haptoglobin, blood smear, complements, serology, urine protein creatine and renal ultrasound with doppler were ordered. Bumetanide and hydralazine for blood pressure control were started. Results came back with schistocytes and thrombocytopenia on blood film, LDH was 1050, haptoglobin (< 14mg/dl) Lambda/Kappa ratio of 1.5, Complements (C3 and C4), ANA, ANCA, Anti DsDNA, SPEP, UPEP, IFE. and CT panel were non-significant, ADAMTS 13 was 32% inconsistent with TTP. Bone marrow biopsy was normal. Patient received five sessions of plasma paresis with no improvement in renal function and patient was started on Eculizumab. A right kidney biopsy eventually showed cute thrombotic microangiopathy possibly malignancy associated in addition to rare hemoglobin staining cast indicating component of tubular injury relating to hemolysis.Eventually, temporary dialysis access was obtained due to worsening renal function. The patient’s hospital course was further complicated by MDR klebsiella pneumoniae urinary tract infection. Patient eventually opted to go home with hospice.
Discussion: TMA’s are rare but heterogenous group pathologies with varied course, causes, and effects. Collectively, they represent a cascade of disarrayed coagulation and complement system dysregulation leading to microangiopathic hemolytic anemia, thrombocytopenia, microthrombi formation, and end-organ dysfunction.Malignancies associated microangiopathies usually arise either as the result of the cancer itself or as treatment sequalae. The two major subtypes are hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. They are commonly found in the setting of mucinous adenocarcinoma but can be found in other malignancies especially with metastatic disease. The pathogenesis is abnormal angiogenesis resulting in endothelial injury with downstream release ultra large VWF multimers, Mucin has also been implicated. Chemotherapy induced TMA is thought to occur by acute immune mediated process or dose dependent toxicity. It can also occur in the setting of bone marrow transplant.
Conclusions: TMA could be an index presentation of malignancy or the complication of the ever-increasing arsenal of anti-cancer therapy, including cellular therapies. A high index of suspicion is needed to improve outcomes and save resources.TMA could be an index presentation of malignancy or the complication of the ever-increasing arsenal of anti-cancer therapy, including cellular therapies. A high index of suspicion is needed to improve outcomes and save resources.