Case Presentation: A 62-year-old female with diabetes, hyperlipidemia, and hypertension presented after a transient episode of left-sided weakness and dysarthria that resolved by the time of arrival to the emergency department. Vital signs were stable except for a blood pressure of 167/92. Physical exam, including a comprehensive neurologic exam, was negative. Urgent stroke workup was pursued including CT head, CTA neck, and MRI head which returned all negative. Labs were notable for a hemoglobin of 8.6 g/dl, MCV 89 fl, platelet count of 28 K/mm3, white blood cell count of 7.6 K/uL, creatinine of 0.74 mg/dl, unconjugated bilirubin of 3.2 mg/dl. Other labs included a haptoglobin < 30 mg/dl, lactate dehydrogenase (LDH) of 713 U/L, and reticulocyte count of 9.3%. Peripheral smear showed moderate amount of schistocytes. Routine admission nasopharyngeal screening swab came back positive for SARS-CoV-2 infection. Patient had no respiratory symptoms and chest x-ray showed no abnormalities. Given the concern for Thrombotic Thrombocytopenic Purpura (TTP), patient was urgently initiated on plasmapheresis and steroids. Further laboratory workup revealed ADAMTS13 activity < 10% and elevated ADAMTS13 antibody at 103 U/ml. Upon discontinuation of plasmapheresis after 5 days, the patient's platelet count relapsed to a nadir of 14K/mm3, which led to reinitiation of plasmapheresis. Weekly rituximab was also started. Platelet count reached >150K by hospital day 18. A repeat ADAMTS13 activity at this time was still < 10%, however ADAMTS13 antibody levels were lowered to 33 U/ml. Given the persistent lack of ADAMTS13 activity recovery, daily caplacizumab was started, with markedly good response.
Discussion: Thrombotic Thrombocytopenic Purpura (TTP) is a life-threatening condition characterized by formation of platelet-rich thrombi in small vessels resulting in hemolytic anemia, thrombocytopenia, and potential end-organ ischemia. TTP can be caused by a broad spectrum of etiologies including autoimmune, malignancy, viral, and pregnancy. In the absence of other common secondary causes, this patient’s acquired TTP was thought to be related to COVID-19 infection. Exact pathophysiology of COVID-19 related TTP is yet to be understood but it is presumed to be due to endothelial injury and autoantibody/immune-complex generation. COVID-19 is increasingly being recognized as a trigger for TTP. Particularly, a recently published systematic review commented on the refractory nature of COVID-19 associated TTP requiring increased number of sessions of plasmapheresis along with other lines of therapy. Our case was unique in that the neurologic complication was the only presenting symptom of TTP. In addition, this case highlighted a severe form of TTP in a patient with asymptomatic COVID-19. This case further demonstrated the atypical and refractory nature of COVID-19 induced TTP in that this patient required 10 rounds of plasmapheresis along with rituximab and caplacizumab to achieve stability. In literature, there are very few reported cases that required all three therapies to treat COVID-19 induced TTP.
Conclusions: TTP is a life-threatening condition that requires prompt recognition and systematic management. Sometimes, neurologic symptoms can be the only presenting sign of COVID-19 associated TTP. Hospitalists should be aware of the association of symptomatic or asymptomatic COVID-19 infection with refractory TTP that may require multiple lines of therapy as this will help guide timely and informed treatment strategies.