Older Patients with iTTP Have Delayed Diagnosis and Higher Mortality Than Younger Counterparts

Older patients diagnosed with immune thrombotic thrombocytopenic purpura (iTTP) have worse short- and long-term mortality compared with younger patients and the general population, according to a study published in Blood. The atypical presentation of iTTP in older adults also can lead to delays in diagnosis, contributing to their worse prognosis, the authors, led by Renaud Prevel, MD, PhD, from the Centre Hospitalier Universitaire de Bordeaux in France, noted.

Approximately 17% of patients with iTTP are 60 years of age or older, the study’s corresponding author, Paul Coppo, MD, PhD, from the Centre de Référence des Microangiopathies Thrombotiques in Paris, told ASH Clinical News. “This work opens new avenues in the field by emphasizing the need to better focus on iTTP in [older people] at a time when new compounds, including anti–von Willebrand factor nanobodies and soon the recombinant form of ADAMTS13, are completing the therapeutic arsenal for this disease.”

In this analysis, Dr. Coppo and co-authors assessed the presentation, treatment, and long-term follow-up data from patients with iTTP enrolled at the French TMA National Reference Center between 2000 and 2016. iTTP diagnosis was defined as the presence of Coombs-negative microangiopathic hemolytic anemia or microangiopathic hemolysis, acute peripheral thrombocytopenia (<150×109/L) with the absence of any other identifiable cause of thrombocytopenia and microangiopathic hemolytic anemia, and severe acquired ADAMTS-13 deficiency (<10% activity) with anti-ADAMTS13 antibodies ≥15 U/mL.

A total of 411 patients were stratified according to age: <60 years (n=340) or ≥60 years (n=71).

Focusing on delays from admission to diagnosis and from diagnosis to treatment, Dr. Coppo and researchers found that older patients had a significantly longer time to diagnosis than younger patients (median = 3 days [range = 1-7] vs. 1 day [range = 1-3]; p<0.0001), while time to treatment start was similar.

The presentation of iTTP differed according to age groups, the researchers reported. At the time of diagnosis, a higher proportion of patients in the ≥60 years group had delirium (30% vs. 18%; p=0.034) and behavior impairment (24% vs. 14%; p=0.045). Older patients also had higher median plasma creatinine (124 μmol/L [range = 89-198] vs. 89 μmol/L [range = 73-120]; p<0.0001), and median elevated troponin levels (0.85 ng/mL [range =0.1-4] vs. 0.26 ng/mL [range = 0.02-1]; p=0.025) at admission.

However, unlike the younger population, cytopenias were less pronounced among older patients, and therefore, not as important to the diagnosis of iTTP: Median platelet counts were 22×109/L (range = 9-57) versus 13×109/L (range = 9-21) in older and younger patients, respectively (p=0.002) and hemoglobin levels were 9 g/dL (range = 8-11) versus 8 g/dL (range = 7-10; p=0.0007).

“Delirium and acute behavioral abnormalities … are very common reasons to admit an old patient,” the authors wrote. “They are not specific to a disease and they are less alarming than in the young patients. This presentation could explain the delayed iTTP diagnosis in this age group.”

Management of iTTP was comparable between age groups: The most common firstline treatment was corticosteroids (84% in the younger group and 77% in the older group), and the most common secondline treatment was rituximab (53% and 44%).

The researchers observed that survival rates differed significantly according to age, in the short and mid term:

  • 1-month mortality: 37% in patients ≥60 years vs. 9% in patients <60 years (p<0.0001)
  • 1-year mortality: 49% vs. 11% (p<0.0001)

Along with age, cardiac involvement (including signs of heart failure, chest pain, electrocardiogram abnormality, or increased troponin level) and increased plasma creatinine levels were independently associated with one-month mortality in patients with iTTP:

  • age >60 years (odds ratio [OR] = 33.3; 95% CI 7.14-1,000; p<0.001)
  • cardiac involvement (OR=5.88; 95% CI 1.11-33.3; p=0.04)
  • increased plasma creatinine level per +10 μmol/L (OR=1.04; 95% CI 1.01-1.1; p=0.01)

Conversely, plasma exchange volume (per +100 mL/kg) was independently associated with lower odds of one-month mortality (OR=0.81; 95% CI 0.60-0.98; p=0.02). In an analysis for one-year mortality, only cardiac involvement remained an independent risk factor for death in older patients (OR=6.67; 97.5% CI 1.89-25; p=0.004).

Next, the authors compared long-term mortality of 38 evaluable older patients with iTTP with that of 1,755 older adults in the general population. After a median of 1,682 days of follow-up (range not reported), a history of iTTP increased mortality risk by more than threefold, after adjustment for cardiovascular and neurologic comorbidities (hazard ratio = 3.44; 95% CI 2.02-5.87; p<0.001).

“This work [emphasizes] the need to better focus on iTTP … at a time when new compounds … are completing the therapeutic arsenal for this disease.”

—Paul Coppo, MD, PhD

“We need to better understand the mechanisms leading to a reduced life expectancy in survivors of an iTTP episode,” Dr. Coppo adds. “These may involve the conjunction of the endothelial alterations related to iTTP, with age-related vascular senescence and other cardiovascular risk factors.”

In light of this information about older patients’ poorer prognosis, the researchers added, “The management of iTTP in the older patients needs to be adapted.” The anti–von Willebrand factor nanobody caplacizumab should become part of the standard treatment of iTTP in the near future, they concluded.

The findings of this analysis are limited by the relatively small number of older patients with iTTP included, as well as the possibilities of data not captured in the registry.

The authors report relationships with Alexion, Ablynx, Shire, Octapharma, and Sanofi.


Prevel R, Roubaud-Roubaud C, Gourlain S, et al. Prognostic and long-term survival of immune thrombotic thrombocytopenic purpura in older patients. Blood. 2019 September 17. [Epub ahead of print]