September 2026 Research Update

Across this group of papers, the main pattern was that measuring ADAMTS13 activity quickly is central to recognizing thrombotic thrombocytopenic purpura (TTP) and can shorten time to a clear diagnosis when symptoms are confusing. The review suggests rapid, automated ADAMTS13 tests can return results in minutes rather than days, and combining test results with clinical probability scores may improve accuracy, although studies differed and were not consistently validated in new settings. Several single-patient reports show TTP can look like stroke or other problems, which can delay recognition without early suspicion and confirmatory testing. [1] [2] [3] [4]

In a systematic review of 14 studies, rapid automated ADAMTS13 activity platforms reduced typical test turnaround from more than 72 hours to about 17 to 35 minutes. Reported test performance was high in several studies (for example, sensitivity 100% with specificities around 94.6% to 98.9% for one rapid platform), and a bedside test returned results in about 10 minutes with sensitivity 100% and specificity 90%. The same review found that clinical scoring tools (such as PLASMIC) and add-on blood markers could help sort higher- from lower-probability cases, but results varied across hospitals and study designs. [1]

A clinical practice guideline described ADAMTS13 activity as the diagnostic gold standard for immune-mediated and congenital TTP, placing it at the center of the diagnostic pathway. The guideline also emphasizes structured follow-up monitoring of ADAMTS13 activity over time, including in situations such as pregnancy where recurrence risk is a concern. [5]

Case reports illustrated how TTP can present in unexpected ways and be mistaken for other emergencies, such as a stroke. One 61-year-old woman with acute neurologic deficits had a high PLASMIC score that prompted urgent TTP-directed care, with later confirmation of severe ADAMTS13 deficiency (below 10%) and clinical improvement. Another patient, a 27-year-old man with stroke-like symptoms and initially negative brain imaging for an acute stroke, was found to have very low ADAMTS13 activity (7.1%) and improved after urgent TTP-directed therapy. [2] [3]

TTP may also start with symptoms that do not primarily sound like a blood disorder. A 40-year-old woman presented with joint pain and later had ADAMTS13 activity below 5%, which confirmed TTP; her symptoms and blood tests improved during the hospitalization after TTP-directed care. Because this is a single case, it mainly shows how broad TTP symptoms can be rather than how often this happens. [4]

For patients and caregivers, this set of papers supports that getting the right diagnosis fast in suspected TTP often depends on quick access to ADAMTS13 activity testing, especially when symptoms resemble other conditions (like stroke) or seem atypical (like prominent joint pain). Some centers may be able to obtain ADAMTS13 results in minutes using rapid platforms, but how well these tools work can vary by hospital and patient population, and more real-world validation is still needed. Guidelines reinforce that ADAMTS13 testing is central not only for initial diagnosis but also for follow-up monitoring, although the best way to implement rapid testing everywhere remains uncertain. [1] [5] [2] [3] [4]

Across these papers, caplacizumab was commonly used alongside plasma exchange and immune-suppressing medicines during acute immune thrombotic thrombocytopenic purpura (immune TTP). A recurring message was that short-term blood count recovery and longer-term recovery of the disease-driving blood enzyme can move at different speeds, and careful tracking of enzyme activity and antibodies helped explain why some patients improved more slowly. [6]

In a retrospective cohort comparing caplacizumab plus plasma exchange versus care without caplacizumab, caplacizumab cases used fewer days of plasma exchange (median 6 vs 12). However, they took longer to reach sustained ADAMTS13 activity above 20% (median 33 vs 17.5 days), and a subset had antibody "boosting" after plasma exchange stopped that was linked to much slower enzyme recovery (median 101 vs 28 days). [6]

A small two-patient case series described how unplanned interruptions of caplacizumab during very low ADAMTS13 activity lined up with disease worsening or delayed improvement, including clot-related (ischemic) complications seen on brain MRI in one patient. After caplacizumab was restarted (and other treatments were adjusted), platelet counts and ADAMTS13 activity improved in both cases. [7]

For patients and caregivers, these reports suggest that even when platelet counts recover, the underlying immune activity (antibodies against ADAMTS13) may still be active in some people, which can affect how long recovery takes and how closely labs are followed. This is mainly near-term, real-world information, but it is not definitive because one study was retrospective and another involved only two patients; it remains uncertain how often antibody boosting happens and which patients are most affected. [6] [7]

The case reports in this group highlight that immune TTP can arise in different real-life situations, including after certain procedures or medication exposures, and that treatment plans sometimes must adapt to what is feasible. Because these are single-patient reports, they show what happened for one person rather than proving what will work for everyone. [8] [9] [10]

One case report described a 45-year-old Jehovah's Witness treated with caplacizumab without plasma exchange (along with steroids, rituximab, and intravenous immune globulin, and later cyclophosphamide). The patient reached clinical remission by day 9, but ADAMTS13 stayed below 5% at 1 month until it rose to 79% after one dose of cyclophosphamide. [8]

Another case report described immune TTP shortly after transcatheter aortic valve replacement in an 87-year-old man who had ADAMTS13 activity below 1% but no symptoms. After treatment with plasma exchange, corticosteroids, caplacizumab, and rituximab, platelet counts recovered quickly after two plasma exchanges. [9]

A separate case report described immune TTP after reexposure to trimethoprim-sulfamethoxazole, with ADAMTS13 activity 4.6% and neurologic changes. After seven plasma exchange sessions plus corticosteroids, the patient improved clinically and in labs, and ADAMTS13 activity normalized. [10]

A broader retrospective cohort from one center in Egypt looked at therapeutic plasma exchange for many illnesses, including TTP. In the TTP subgroup, complete remission was reported in 77.8%, and the study also reported mostly mild procedure-related side effects (grade 1 to 2), such as low blood pressure and allergic reactions. [11]

For patients, these papers mainly provide context: immune TTP treatment in the real world may involve combinations of plasma exchange and immune treatments, and rare triggers (like a medication reexposure or a recent procedure) were described in single cases. What remains uncertain is how often these situations occur and how much the reported outcomes depended on each person's overall health and the exact treatment mix, since most evidence here is from case reports and one single-center retrospective study. [8] [9] [10] [11]

Across these small reports, hereditary thrombotic thrombocytopenic purpura (TTP) was hard to recognize during pregnancy and right after birth because it can overlap with more common problems (such as HELLP syndrome in pregnancy or severe illness in newborns). Testing for ADAMTS-13 activity (a blood protein involved in clotting control) and confirming ADAMTS-13 gene changes helped clarify the diagnosis and guide care. Because these are case-level reports, they show what can happen but cannot predict outcomes for most families. [12] [13]

One case report described a 27-year-old pregnant woman at 21 weeks whose illness was initially consistent with HELLP syndrome but also fit hereditary TTP, creating a diagnostic challenge. Her ADAMTS-13 activity was undetectable with a negative inhibitor test, and genetic testing found two heterozygous pathogenic ADAMTS-13 variants that confirmed hereditary TTP. After emergent delivery and several days of plasma exchange, her platelet count improved and liver tests normalized, and she had no lasting neurologic problems reported; the fetus was not viable. [12]

A separate case series followed three siblings with hereditary TTP caused by ADAMTS-13 loss-of-function variants, all of whom needed neonatal exchange transfusions. Despite severe newborn illness, they were not diagnosed until ages 13 to 18, and their early history included a neonatal stroke in one sibling and a childhood leukemia workup in another. Two of the adults were receiving recombinant ADAMTS-13, and the authors proposed a step-by-step approach to improve newborn recognition and potentially reduce the need for exchange transfusions. [13]

For patients and caregivers, this set of papers mainly adds context about why hereditary TTP can be overlooked during pregnancy and in newborns, especially when it resembles other conditions that are more common. It also highlights that ADAMTS-13 activity testing and genetic confirmation can help sort out the cause in complex situations, which may matter for understanding risks in future pregnancies and for family planning discussions. What remains uncertain is how often these situations occur and which specific testing approaches work best in different hospitals, because the evidence here comes from one case report and one small family series. [12] [13]

Across this group of papers, two messages stood out: (1) a clearer map of the different ADAMTS13 gene changes reported in congenital thrombotic thrombocytopenic purpura (congenital TTP), and (2) strong clinical trial evidence that recombinant ADAMTS13 can prevent episodes more effectively and with fewer treatment-related side effects than plasma-based prevention. The genetics work is exploratory and mainly helps with understanding and classification, while the prevention study provides higher-strength, patient-level evidence. [14] [15]

A research team compiled 385 ADAMTS13 variants reported worldwide into an online database and used computer-based tools to annotate both protein-coding and non-coding variants. Variants were spread across the gene, but were especially common in the metalloprotease part of the ADAMTS13 protein, which is important for its function. [14]

In that database work, variants located toward the N-terminal (front end) of the protein were linked to earlier symptom onset and lower remaining (residual) ADAMTS13 activity. In plain language, this suggests that where a gene change occurs may relate to how early congenital TTP shows up and how much enzyme activity is left. [14]

In a randomized phase 3 open-label crossover trial of 48 people aged 3 to 68 years with congenital TTP, no acute TTP events occurred during recombinant ADAMTS13 prevention, while 1 acute event occurred during plasma-based prevention. Subacute TTP events and low-platelet events were also lower during recombinant ADAMTS13 periods, and ADAMTS13 activity increased by about sixfold with more time spent at or above 10% activity. [15]

Safety and day-to-day experience also differed in the trial: treatment-related side effects were reported in 4.3% of participants during recombinant ADAMTS13 prevention versus 45.8% during plasma-based prevention. No serious side effects were linked to recombinant ADAMTS13, and no ADAMTS13-neutralizing antibodies were detected; participants also reported greater treatment satisfaction on recombinant ADAMTS13. [15]

For patients and caregivers, this set of studies separates into background knowledge and direct care evidence. The gene-variant database may help researchers and laboratories describe and interpret ADAMTS13 variants more consistently, including hints that some gene regions relate to earlier onset and lower enzyme activity, but it does not by itself determine what will happen for any one person. The prevention trial is more immediately relevant because it tested a specific preventive approach in people with congenital TTP and reported fewer episodes, higher ADAMTS13 activity, fewer treatment-related side effects, and higher satisfaction during recombinant ADAMTS13 compared with plasma-based prevention; questions that remain include how results apply across all rare variants and longer time spans beyond the study periods. [14] [15]

Across these papers, immune thrombotic thrombocytopenic purpura (TTP) was linked with complications beyond low platelets, including the brain, heart, kidneys, and pancreas. Evidence ranged from a small prospective MRI study to individual case reports, so the overall picture is clearer about what can happen, but less certain about how often and in whom. [16] [17] [18]

In a prospective cohort of 25 adults with acute immune TTP, brain MRI showed two main patterns: acute small strokes during the acute episode and a higher burden of cerebral small vessel disease compared with age-matched controls. Over 12 to 18 months, MRI signs of small vessel disease became more common and some people had worsening scores, suggesting that brain changes may continue even after the acute event. [16]

One case report described a 73-year-old woman with influenza A-associated immune TTP who had a large vessel blockage in a major brain artery and underwent mechanical clot removal. Even though blood flow was restored and plasma exchange and steroids were started, her neurologic condition worsened and care was changed to comfort measures, highlighting the high stakes and complexity when severe low platelets and a major stroke occur together. [17]

A separate case report described a 43-year-old man whose first signs of TTP were acute pancreatitis and a non-ST-elevation heart attack. After plasma exchange and steroids, his laboratory tests and symptoms improved and he remained in clinical remission without recurrence at 1 and 6 months, showing that TTP can present with serious non-brain organ involvement and still improve with standard TTP-directed care in an individual patient. [18]

For patients and caregivers, these reports add context that TTP can affect multiple organs, including the brain (from small vessel injury seen on MRI to major artery stroke in a rare case), as well as the heart and pancreas in some people. The MRI study suggests some brain vessel changes may progress over the year after an acute episode, but it was small and does not prove that everyone will have ongoing brain changes. The case reports describe single individuals, so they help illustrate what is possible but cannot predict outcomes for others. [16] [17] [18]

Across this month s research in future therapies, one preclinical study focused on redesigning the ADAMTS-13 protein so it can do two jobs at once: cut down overactive von Willebrand factor and also reduce platelet sticking. The work is at an early stage (lab experiments only), so how well it would work or how safe it would be in people is still unknown. [19]

Researchers engineered fusion constructs that combine an ADAMTS-13 fragment with a single-domain antibody that targets active von Willebrand factor. In biochemical and functional lab tests, the constructs kept their ability to cut von Willebrand factor and reduced platelet-von Willebrand factor interactions, which are key steps in clot formation in thrombotic thrombocytopenic purpura. [19]

One version, called MDTCSm-aVWF, showed stronger cutting activity and was more resistant to interference from autoantibodies found in plasma from people with immune-mediated thrombotic thrombocytopenic purpura. In plain terms, this suggests a possible way to design a treatment that continues working even when the immune system blocks standard ADAMTS-13. [19]

This work mainly matters as background research for the future, because it was done in lab systems rather than in people. It suggests one possible direction for new treatments that could both reduce von Willebrand factor driven clotting and be less affected by immune antibodies, but important uncertainties remain, including safety, dosing, durability, and whether the same effects occur in the human body. [19]