A 19-year-old man was admitted with acute non-radiating epigastric pain associated with three episodes of non-bilious/non-bloody emesis. He denied fever, diarrhea or hematuria. Review of systems was positive for muscle aches. His physical examination was unremarkable for any rebound tenderness or hepatosplenomegaly. Complete blood count demonstrated thrombocytopenia (93000/uL) with normal hemoglobin. Comprehensive metabolic panel was significant for elevated BUN (33mg/dl) and creatinine (2.65mg/dl); total bilirubin and AST were also mildly elevated at 2.2 mg/dl and 85U/L, respectively. Urinalysis showed mild proteinuria and hematuria. Serum creatine kinase was also elevated (2237U/L). His lactate dehydrogenase (LDH) was mildly elevated at 374U/L (likely due to rhabdomyolysis). C3, C4 and haptoglobin levels were within normal range. Peripheral smear failed to demonstrate schistocytes. The patient’s kidney function continued to deteriorate prompting a kidney biopsy which was non-diagnostic.
On hospital day 4, the patient developed the “worse headache of his life” with sudden blindness. His labs demonstrated worsening thrombocytopenia (25000/uL), and acute kidney injury (4.38mg/dl) as well as coagulopathy with INR of 1.5. A non-contrast computed tomography of the brain was significant for intracerebral hemorrhage and subarachnoid hemorrhage as well as vasogenic edema in a distribution suggestive of PRES (posterior reversible encephalopathy syndrome). Later, he became hypotensive, with physical examination significant for elevated jugular venous pressure and pulsus paradoxus; a bedside echocardiogram demonstrated cardiac tamponade requiring emergent pericardiocentesis. Although the patient did not have any signs of hemolytic anemia, the worsening thrombocytopenia in presence of renal and neurologic dysfunction led to the suspicion of atypical thrombotic thrombocytopenic purpura (TTP). Plasmapheresis was initiated, and his renal function and platelet count significantly improved. ADAMTS13 activity was noted to be <5%, confirming the diagnosis of TTP.
TTP is rare with an incidence of approximately 3 cases per million adults per year. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia and hemolytic anemia. Pathogenesis is related to severe deficiency of ADAMTS13 protease activity, clinically defined as activity level <10%. Initial symptoms can range from fatigue to encephalopathy and focal neurologic deficits. Abdominal pain may be a presenting symptom in 25% of the patients. The classic pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, acute renal failure or insufficiency, and neurological findings is infrequent due to early initiation of treatment. TTP is a medical emergency that can be fatal if appropriate therapy is not initiated promptly.
TTP presenting in the absence of MAHA is very rare. In patients who present with signs or symptoms consistent with TTP, but without MAHA, a high index of suspicion is required to diagnose atypical TTP. Laboratory findings of thrombocytopenia, elevated LDH and creatinine, and reduced activity of ADAMST13 support the diagnosis. Early treatment with plasmapheresis is life-saving and can prevent fatal outcomes.