Brazil study shows early diagnosis is key to better outcomes in TTP
Researchers in country find higher risk of death tied to delayed care
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Timely diagnosis of thrombotic thrombocytopenic purpura (TTP) and access to newer treatments could improve survival and reduce complications for people in Brazil with the rare bleeding disorder, a new study by a Brazilian research team suggests.
The scientists found that gaps in care across the country were linked to a higher risk of death for people with TTP, and also to long-term neurological and psychological complications among survivors.
“TTP diagnosis and treatment in the country are delayed and outdated, negatively affecting disease prognosis,” the researchers wrote, noting that many patients — both in Brazil and in other low- and middle-income countries — have limited access to timely medical care.
“Ensuring rapid diagnosis and the availability of … a cost-effective treatment strategy, is essential for improving outcomes and reducing [the risk of death]” for these patients, the team wrote.
Their study, “Brazilian Registry of Thrombotic Thrombocytopenic Purpura: A prospective cohort study of diagnosis, management and outcomes in Brazil,” was published in the journal Thrombosis Research.
In TTP, small clots form in blood vessels, restricting blood flow to the body’s organs and causing a range of symptoms. In immune-mediated TTP, the most common form of disease, this occurs because antibodies mistakenly attack ADAMTS13, an enzyme that normally helps prevent excessive clotting.
Standard TTP treatment relies on therapeutic plasma exchange (TPE), which replaces a patient’s plasma — the portion of blood without cells — with healthy donor plasma to remove harmful antibodies. This helps restore ADAMTS13 activity. Corticosteroids, a type of steroids, are typically given alongside TPE to suppress the underlying autoimmune response. However, such medications, especially when given over the long term, are linked to serious side effects.
Newer treatments have further improved outcomes for people with ITP. Rituximab, a medication that reduces antibody-producing immune cells, lowers the risk of relapse, while Cablivi (caplacizumab-yhdp), a drug approved for TTP in combination with TPE and immunosuppressive therapy, helps prevent blood clot formation by blocking a key clotting protein. Such treatment can speed up recovery and reduce early complications.
Scant data on TTP diagnosis, treatment in Brazil
The issue for clinicians and patients in some countries, however, is getting access to these newer medications.
“Most of the evidence supporting these advances comes from high-income regions, with data largely derived from North American, European, and Asian registries,” the researchers wrote. “In contrast, little is known about the access, implementation, and impact of recent TTP diagnostic and therapeutic strategies in low- and middle-income countries.”
Further, “data on the demographics, epidemiology, and clinical manifestations of TTP in these regions are also scarce,” the team noted.
To address this gap, the research team conducted a prospective study involving 85 people with TTP at eight medical centers across Brazil. Patients were enrolled between 2018 and 2024 and were monitored for up to one year after hospital discharge.
About three-quarters of the participants were women, and the median age was 37. Most cases (92%) were classified as idiopathic, meaning no clear underlying cause was identified; the remaining patients had health conditions to which TTP was linked. About 14% were experiencing a relapse, meaning they had a previous TTP episode in the past.
Neurological problems — such as confusion, severe headache, movement difficulties, or sensory changes — were the most common symptoms, affecting about three-quarter of patients. Bleeding symptoms, such as small red or purple spots on the skin, occurred in nearly 60%, and about one-third had abdominal complaints such as pain, nausea, or diarrhea.
Although early symptoms were common, hospital admission typically did not occur until a median of 7-8.5 days after symptom onset, depending on the presenting symptom.
ADAMTS13 activity levels, key to confirming TTP, were tested in 62% of patients. All of those tested showed very low enzyme activity, consistent with the diagnosis.
The researchers noted that the limited availability of this testing in Brazil’s public health system means doctors often must rely on symptoms and routine lab results to guide diagnosis.
4 patients in study died before treatment could begin
Most patients (87%) received TPE, but four died before treatment could begin, underscoring the importance of timely intervention, according to the researchers.
Treatment was started a median of one day after hospital admission, the data showed. However, 25% of patients — 1 of every 4 — did not begin TPE until more than two days after admission.
Nearly all patients (95%) were given corticosteroids. Meanwhile, fewer than 60% received rituximab. Three patients were given Cablivi, reflecting limited access to newer therapies, the team noted.
Despite treatment, 55 patients (65%) required admission to an intensive care unit, with 27% needing mechanical ventilation to assist with breathing. A total of 13 patients (15%) died during hospitalization. Those who died were generally older than those who survived (median 49 vs. 33.7).
This death rate was higher than in recent reports from wealthier countries, the researchers noted.
“Our hypothesis is that TPE availability, timing of TPE initiation and rituximab availability influenced the overall prognosis in our TTP [group],” the team wrote.
Our findings reinforce that TTP remains a time-sensitive [bleeding disorder] emergency in which early recognition and prompt initiation of [therapeutic plasma exchange], combined with corticosteroids and rituximab, are essential to improve survival and prevent relapse.
Lingering health problems were common among those who survived. Within a year after discharge, nearly 1 in 5 patients (17%) reported persistent neurological or psychological symptoms, including headaches, memory or concentration difficulties, and anxiety. Patients who had neurological symptoms during hospitalization were more likely to have lasting effects, the team noted.
In addition, 8% experienced a relapse after their initial episode. Treatment with rituximab was associated with a lower risk of relapse.
“Our findings reinforce that TTP remains a time-sensitive [bleeding disorder] emergency in which early recognition and prompt initiation of TPE, combined with corticosteroids and rituximab, are essential to improve survival and prevent relapse,” the researchers concluded. “Unfortunately, TTP diagnosis and treatment in Brazil are more than 10 years outdated, negatively affecting disease prognosis.”
The team added that “health policy measures aimed at expanding diagnostic capacity for ADAMTS13 testing and ensuring equitable access to TPE and rituximab across the country could markedly improve outcomes.”
