Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterized by thrombocytopenia, hemolytic anaemia, fluctuating neurological deficits, fever, and kidney failure. This clinical case is about a young man who presented with acute-onset right-sided paralysis, dysarthria, and central facial paralysis, suggestive of the cerebrovascular accident but finally diagnosed as TTP. In addition, the clinical presentation of TTP is discussed and some teaching points for emergency physicians are emphasized.
Keywords: thrombotic thrombocytopenic purpura, emergency department, acute ischemic stroke, dysarthria.
Report of a case
A previously healthy 36-year-old man came to our emergency department (ED) with right arm weakness, numbness on the right side of the face, and difficulty speaking, which developed an hour before the presentation. He had had a fever, cough, headache, and bleeding gums for 10 days. On examination, the patient’s blood pressure was 160/100 mm Hg, pulse 94 beats/min, respiratory rate 14 breaths/min, and temperature 38.0 ° C. Neurological examination revealed 2/5 arm weakness right, 4/5 weakness of the right leg, dysarthria and right central facial palsy. There was no stiff neck or cerebellar abnormalities.
After blood was drawn for lab tests, he underwent a cranial computed tomography (CT) scan in 30 minutes. The computed tomography did not show intracranial or subarachnoid haemorrhage or signs of ischemia. After another half hour, his neurological findings resolved. A diagnosis of transient ischemic attack was considered an admission to neurology was planned.
Laboratory test results were unexpected: white blood cell count 12,000 × 109, hemoglobin 74 g / L (7.4 g / dL), hematocrit 0.21 (21.1%), and platelet count 11,000 × 109 Urea, creatinine, electrolytes, and liver function were normal. Urinalysis was remarkable with +3 erythrocytes. Indirect bilirubin and lactate dehydrogenase levels were elevated. Intravascular hemolysis was suspected and a blood smear was requested. Three hours after presentation, the previous neurological symptoms reappeared for one hour and then gradually resolved again.
Intravascular hemolysis, thrombocytopenia, hematuria, fluctuating neurologic findings, and fever were consistent with a diagnosis of TTP. The patient was admitted and underwent emergency plasmapheresis. He did not present any neurological symptoms during the course of treatment. Complete remission was achieved on day 12 after admission and he was discharged on day 16.
TTP is a life-threatening disease characterized by thrombocytopenia, microangiopathic hemolytic anaemia, fluctuating neurological signs, kidney failure, and fever. The condition is rare with an annual adult incidence of 3.7 per million. It is predominantly seen in women, generally between the ages of 30 and 401.
The pathogenesis of TTP is attributed to the presence of unusually large von Willebrand factor (vWF) multimers leading to platelet agglutination and consequent microvascular thrombosis. These vWF multimers are normally cleaved into smaller protein units by a metalloprotease enzyme, von Willebrand factor cleavage protease (ADAMTS-13). Impaired ADAMTS-13 activity leads to excessive accumulation of vWF, which can then lead to the appearance of TTP. TTP is primarily idiopathic but can be triggered by clinical conditions such as bacterial or viral infections, pregnancy, drugs (eg, clopidogrel, ticlopidine, quinine, cyclosporine), and autoimmune disorders (systemic lupus erythematosus, thyroiditis, and antiphospholipid syndrome).
Identifying the first acute episode of TTP is challenging, as no specific clinical symptoms or biological criteria are available for diagnosis. Suspicion of TTP is based on the association of several clinical symptoms and laboratory results. The brain is the most common target for ischemia, and abnormal neurologic findings are present in most cases of TTP. Patients often develop headaches, confusion, ataxia, seizures, and focal and mental status abnormalities.
Other common symptoms are fever, weakness, arthralgia, myalgia, jaundice, nausea, vomiting, diarrhoea, and abdominal pain. Cutaneous and mucosal bleeding secondary to thrombocytopenia is also common2,3. Patients may present with renal abnormalities, such as oligoanuria, acute renal failure, albuminuria, and microscopic hematuria. Consumption thrombocytopenia is present in most cases, with platelet counts often less than 20,000 × 109.
According to the 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, our patient was a candidate for thrombolytic therapy for ischemic stroke within the first two hours after presentation. However, right-sided weakness, central facial palsy, and dysarthria have been reported to be associated with TTP.
These neurological manifestations of TTP can easily be mistaken for an acute ischemic stroke, which requires early thrombolysis. Administration of thrombolytic drugs to patients with TTP misdiagnosed as acute ischemic stroke can have detrimental consequences. Therefore, laboratory test results for patients with signs and symptoms of an acute ischemic stroke should be carefully monitored and TTP should be considered as a differential diagnosis.
Prompt diagnosis and treatment are necessary to decrease the risk of fatal outcomes in patients with TTP. Emergency physicians must be familiar with the clinical presentation and laboratory abnormalities of TTP in order to make an early diagnosis. In patients with fluctuating neurologic findings, thrombocytopenia, hemolytic anaemia, and fever, the diagnosis of TTP should be considered.