Abstract

Background:

Immune Thrombotic Thrombocytopenic Purpura (iTTP) is a rare life-threatening thrombotic microangiopathy. TTP is clinically defined as microangiopathic hemolytic anemia and thrombocytopenia in adults without an alternative cause. The other three symptoms in the classical pentad - fever, altered mental status and kidney injury - are no longer mandatory for diagnosis. iTTP is defined by a deficiency in ADAMTS13, a protease that cleaves von Willebrand Factor. Laboratory confirmation of ADAMTS13 deficiency plus autoantibodies and/or inhibitors is frequently delayed. Therefore, early clinical suspicion of iTTP is imperative in order to initiate treatment and decrease mortality.

The presenting symptoms and demographics of patients with iTTP have been previously reported by the Oklahoma TTP registry (Vesely, 2003). This registry consists of 142 patients from Oklahoma with idiopathic TTP, a subset of which was deficient in ADAMTS13. In this abstract we present a descriptive analysis of demographics and presenting symptoms in patients with laboratory-confirmed iTTP from the USTMA TTP registry; an eight-institution registry spanning six US states. Additionally, we compared the presenting symptoms and demographics of our registry with the findings in the Oklahoma TTP registry.

Objectives:

To report demographics and the prevalence of specific precipitating events and presenting symptoms of iTTP in patients enrolled in the USTMA TTP registry.

Methods:

Following IRB approval at each institution, investigators independently reviewed patient records and any patients who met the determined definition of iTTP were included in the registry. Immune TTP was defined as ADAMTS13 < 10% or ADAMTS13 < 20% with an inhibitor or antibody detected. Demographic and disease-related information, including precipitating events, presenting symptoms was collected by review of electronic medical records.

Results:

181 patients with 316 distinct episodes of confirmed iTTP are currently included in the USTMA TTP registry. Demographic and clinical data are reported in Tables 1 and 2. The majority of patients who presented with TTP were female (74%). The ethnicity of patients was almost evenly split between Caucasian (49.2%) and Black or African American (44.1%). In comparison, the Oklahoma registry was 80% female and 37% Black or African American, differences that are not statistically significant (p 0.3 and p 0.1). No precipitating event was identified in the majority of episodes (76.4%). Infection was most common (13.5%) followed by initiation of new medications or supplements (8.8%). The most common presenting symptoms of iTTP included petechiae or easy bruising (25.7% of episodes), focal neurologic deficits (23.8%) and fatigue (22.8%). Other common symptoms included other neurologic findings including confusion (16.3%) and headache (18.6%), as well as fever (13.7%) and abdominal pain (18.6%). Many episodes had multiple symptoms and in 20.8% of episodes there were no reported symptoms.

18 patients in the Oklahoma registry met our inclusion criteria and we compared the symptoms of our patients to that cohort (Vesely, 2003). The most common symptoms in their cohort were gastrointestinal (55%), higher than we observed although we only specifically measured abdominal pain. Notably, they had a similar percentage of patients present with severe neurologic findings (28%), which included focal neurologic deficits. This observation of focal deficits is potentially interesting given that TTP-associated neurologic symptoms have more commonly been described as global deficits including altered mental status.

Conclusions:

iTTP is a rare, life-threatening disease that requires prompt identification and treatment. The USTMA TTP registry is the largest and only multicenter US iTTP registry to date. It offers the opportunity to analyze and report the demographics and common presenting symptoms of iTTP to aid in recognition and diagnosis. When compared with the Oklahoma TTP registry, the best-studied iTTP cohort in the US, we found similar demographic distributions, with both women and African-Americans being overrepresented. We also found similar proportions of patients who presented with focal neurologic symptoms, as opposed to the more commonly described altered mental status. Abdominal pain/GI symptoms were less frequent in the USTMA TTP registry compared with the Oklahoma TTP registry.

Disclosures

Sadler: BioMarin: Consultancy; Genentech: Consultancy; Ablynx: Consultancy; 23andMe: Consultancy.

Author notes

*

Asterisk with author names denotes non-ASH members.