A 46-year-old previously healthy woman comes to the emergency department due to 4 days of intermittent fever, abdominal pain, and vomiting. For the past 2 days, she has also had decreased urine output, skin rash, and progressive lethargy. Temperature is 38.3 C (101 F), blood pressure is 130/80 mm Hg, and pulse is 100/min. There is a scattered petechial rash, facial puffiness, and 1+ bilateral pedal edema on physical examination. Laboratory results show hemoglobin of 8.9 g/dL with elevated reticulocyte count and a platelet count of 26,000/mm3. Bleeding time is prolonged; PT and activated PTT are normal. The peripheral blood smear shows schistocytes and reduced platelets with presence of giant forms. Blood urea nitrogen is 46 mg/dL and serum creatinine is 2.3 mg/dL. Urinalysis is positive for proteinuria and hematuria. Which of the following is most likely to be seen on this patient's renal biopsy?
This patient with a pentad of fever, neurologic symptoms (eg, progressive lethargy), renal failure, anemia, and thrombocytopenia has schistocytes on peripheral blood smear, which is indicative of thrombotic microangiopathy (TMA) (eg, thrombocytopenic thrombotic purpura [TTP]). TMA syndromes have varying etiologies but share common clinical and pathologic features, including:
Unlike disseminated intravascular coagulation, in which coagulation cascade activation leads to prolongation of coagulation studies (PT and activated PTT), TTP is almost always characterized by normal PT and activated PTT. The diagnosis can be confirmed with histopathology, which typically shows thrombi in small blood vessels (eg, glomerular capillaries, arterioles).
(Choice A) Histopathology in focal segmental glomerulosclerosis shows collapse and sclerosis of a segment of the glomerular tuft and characteristically affects some, but not all, glomeruli. Although it commonly manifests with proteinuria and edema, thrombocytopenia and anemia with schistocytes would not be expected.
(Choice B) Crescent formation is characteristic of rapidly progressive glomerulonephritis, which typically presents with macroscopic hematuria, hypertension, and progressive renal failure; it is caused by severe immunologic injury (eg, anti–glomerular basement membrane antibodies, immune complex deposition). This patient's thrombocytopenia and anemia with schistocytes are more suggestive of TMA.
(Choice C) Poststreptococcal glomerulonephritis is microscopically characterized by hypercellular glomeruli with subepithelial immune deposits. It typically affects children following streptococcal infection and can lead to increased cola-colored urine output and periorbital edema.
(Choice D) Henoch-Schönlein purpura is typically a childhood disease with nonthrombocytopenic palpable purpura and arthralgias; IgA nephropathy commonly presents with recurrent hematuria and low-grade proteinuria following an upper respiratory tract infection. Both diseases show IgA deposition in the mesangium.
(Choice E) Acute tubular necrosis due to ischemia (eg, prolonged hypotension) or nephrotoxins (eg, antibiotics, myoglobin) generally presents with rising creatinine and muddy brown granular casts on urinalysis.
Educational objective:
Primary thrombotic microangiopathy (TMA) syndromes share common clinical and pathologic features and result in platelet activation and diffuse microthrombosis in arterioles and capillaries. They present with hemolytic anemia, schistocytes, thrombocytopenia, and organ injury (eg, brain, kidneys).