A 33-year-old woman presents with confusion, abdominal pain, and fever. Her vital signs are:

• Blood pressure of 118 over 93
• Heart rate of 120
• Respiratory rate of 18

She has a history of lupus. CBC shows a thrombocytopenia of 27 x 109/L platelets.

What is the best management of this condition?

For six decades, the pentad of fever, thrombocytopenia, hemolytic anemia, renal injury, and neurological manifestations has remained the classic clinical diagnostic criteria for Thrombotic Thrombocytopenic Purpura (TTP).¹ Unfortunately, fewer than 10 percent of patients present with this constellation of symptoms. Although the treatment of TTP has improved significantly over the past 30 years, the disease still has a dangerously high mortality rate of approximately 20 percent. Most of these deaths can be attributed to a delay in diagnosis.²

TTP often presents abruptly, and most patients that develop it first visit the emergency department (ED) as their symptoms worsen. It is thus imperative that emergency physicians be able to recognize and properly treat this disease, especially in the absence of its classical presentation.³

In TTP, patients undergo microangiopathic hemolytic anemia that leads to severe thrombocytopenia and, in severe cases, organ dysfunction. The disease may be congenital (cTTP) or immune-mediated (iTTP). The vast majority of cases are immune-mediated, with 90 percent presenting in adulthood, typically with a first incidence between 30-50 years of age.⁴ Women have a two to three times increased risk, and African-American patients have an eight-fold increased risk compared to the general population.¹ Both cTTP and iTTP are caused by a deficiency in ADAMTS13, an enzyme that regulates Von Willebrand Factor (VWF) multimers. When severe ADAMTS13 deficiency—less than 10 percent—is present, there is no regulated proteolysis of VWF, directly leading to uncontrolled platelet adhesion and aggregation. In TTP, this ultimately manifests as microvascular thrombosis, endothelial damage, and organ dysfunction.¹ iTTP is primarily due to acquired anti-ADAMTS13 antibodies, which can be either inhibitory via neutralization of the proteolytic function of ADAMTS13 or non-inhibtory, accelerating the clearance of ADAMTS13 from the circulatory system. Even relatively small amounts of anti-ADAMTS13 autoantibodies can lead to TTP.¹

Primary iTTP has no defined cause, but secondary iTTP has been associated with a number of etiologies, including pregnancy, autoimmune disorders, HIV infection, malignancy and iatrogenic medications.⁴

Diagnosis

Fewer than 10 percent of patients with TTP present with the classical clinical pentad of fever, microangiopathic hemolytic anemia, thrombocytopenia, neurological deficits, and renal insufficiency.¹ However, many clinical features are common: more than 60 percent of patients present with a degree of neurological involvement, ranging from confusion to stroke and coma.¹ 35 percent of patients present with gastrointestinal symptoms secondary to ischemic microthrombi.¹ 25 percent of patients may present with evidence of myocardial ischemia, including abnormal ECGs and elevated troponin levels.¹ Laboratory testing will show significant thrombocytopenia (below 30 x 109/L), in addition to markers of hemolysis such as erythrocyte fragmentation and elevated LDH.¹