Case Presentation: The patient is a 53-year-old female with a past medical history of thrombotic thrombocytopenic purpura (TTP), asplenia, hypertension, hepatitis C, patent foramen ovale with closure, and multiple strokes who presented to our institution with a three-day history of dysequilibrium and nausea. The patient’s TTP was initially diagnosed at 19 years of age during admission for prolonged uterine bleeding during her first pregnancy, which was treated with plasmapheresis (PLEX), steroids and splenectomy. She had a recurrent episode of TTP during her third pregnancy at age 25. She also had an episode of TTP after a cholecystectomy at age 49, treated with PLEX and steroids.She suffered her first stroke two years prior to presentation and was started on aspirin and statin. At this time, she was found to have a PFO on TEE which was repaired. She remained compliant on medical therapy and yet suffered a repeat stroke to the right corona radiata seven months later. Afterwards, she was switched from aspirin to clopidogrel, and remained on a statin for stroke prevention. Despite being on optimal medical therapy, the patient suffered a third stroke to the left cerebellum just one month later. Clopidogrel was then discontinued and she was started on apixaban 5mg twice daily. She had been adherent to apixaban when she presented to our institution.Neurologic examination was significant for subcortical slowing and aphasia from prior strokes, and a new left upper extremity ataxia. MRI revealed new ischemic changes in the left anterior cerebral artery territory of the frontoparietal cortex, confirming diagnosis of new stroke. Hematology was consulted on hospital day 2. The patient had a normal platelet count of 208,000/uL, elevated LDH of 281 unit/L, and haptoglobin of 159 mg/dL. Given her history of TTP, ADAMTS13 level, peripheral smear, and repeat hemolysis labs were obtained. The patient was continued on clopidogrel and apixaban. She was transfused two units of fresh frozen plasma (FFP) prophylactically. The patient was discharged in stable condition. ADAMTS13 activity level resulted after discharge at <3% with presence of inhibitor at titer of 1.3 BEU.
Discussion: Our patient presented with an acute stroke having normal platelets, mildly elevated LDH and normal haptoglobin, making this an atypical presentation of TTP. While her history was initially strongly suggestive of hereditary TTP, the presence of an inhibitor points to the fact that this is more likely an atypical presentation of the acquired form. It is likely that the three strokes she suffered prior to this presentation were also manifestations of her TTP. Treatment of hereditary TTP involves prophylactic plasma infusions, which may be advisable in our patient given her history of frequent relapse on optimal medical therapy.
Conclusions: Because of the high mortality when untreated, particular attention should be paid to young or middle-aged individuals who present with recurrent strokes in the absence of obvious cardiovascular risk factors, even if the setting of normal platelet counts. There are rare reports of atypical TTP presenting initially as either pulmonary embolism or myocardial infarction prior to the development of thrombocytopenia or hemolysis. Thrombosis may precede the development of laboratory abnormalities in patients with either congenital or acquired TTP. Decreased ADAMTS13 activity is highly specific for diagnosis of TTP, and can play a role in timely therapy with either total plasma exchange or administration of FFP.