May 2026 Research Update

Across this group of papers, the main message was that diagnosing immune thrombotic thrombocytopenic purpura (TTP caused by an immune problem) often depends on combining clinical clues with targeted blood tests, because several other conditions can look similar at first. A large validation study suggested a commonly used scoring approach can be refined by swapping out a weaker blood-measurement component for a stronger one, although accuracy dropped in older adults. Two single-patient reports showed how TTP and non-TTP conditions can be mistaken for each other early on, including situations involving gallbladder inflammation or vitamin deficiency. [1] [2] [3]

In a multicenter retrospective study of people who had ADAMTS13 testing (a key lab test used to classify immune TTP), the original PLASMIC score showed good overall ability to separate immune TTP from controls, but one component (mean cell size of red blood cells) did not independently predict immune TTP. In contrast, higher lactate dehydrogenase (LDH, a blood marker that can rise with tissue damage and red cell breakdown) was a strong independent predictor, and a modified version that removed mean cell size performed modestly better overall. The study also reported that diagnostic performance was consistently lower in patients age 60 years and older across the original and modified versions. [1]

A separate cross-sectional study looked at immature platelet fraction and immature platelet count, which reflect how actively the bone marrow is releasing new platelets. These measures helped distinguish thrombocytopenia mainly from peripheral platelet destruction/consumption (a group that included immune thrombocytopenia and thrombotic thrombocytopenic purpura) versus thrombocytopenia from bone marrow failure causes like chemotherapy or leukemia. In plain terms, the test pattern tended to differ when platelets were being used up or destroyed in the bloodstream compared with when the marrow could not make enough platelets. [4]

Two case reports highlighted specific "lookalike" situations where early impressions can change as more information comes in. One report described an African-American woman with systemic lupus erythematosus who had acute gallbladder inflammation without gallstones along with TTP; she was first treated as immune thrombocytopenia without improvement, and later low ADAMTS13 activity supported TTP. Another report described a 60-year-old man with chronic alcohol use whose folate deficiency caused a pseudo-thrombotic microangiopathy with schistocytes and low blood counts; testing and bone marrow findings argued against true TTP, and his blood counts improved after folate supplementation and transfusion. Because each report describes one patient, the exact presentation may not apply to most people. [2] [3]

For patients and caregivers, these studies reinforce why the evaluation of suspected TTP often uses multiple lab signals, including specialized tests (like ADAMTS13) and other blood markers that can help tell platelet destruction or use-up (as in TTP or immune thrombocytopenia) apart from bone marrow problems, and TTP apart from vitamin-related mimics. The larger study suggests some score components may contribute less than others and that accuracy can be lower in older adults, which is important background when results are not clear-cut. The case reports mainly matter as context: uncommon situations (such as autoimmune disease with gallbladder inflammation, or folate deficiency with TTP-like blood smear changes) can confuse the early picture, and it remains uncertain how often these patterns occur outside individual reports.

This month, the papers showed that inherited thrombotic thrombocytopenic purpura (TTP) can be caused by many different changes in the ADAMTS13 gene, including variants not previously reported. They also showed that even when a genetic cause is identified, it may not clearly predict how the illness will look in day-to-day life or which organs will be most affected. [5]

In a genetic analysis of 45 unrelated Russian patients with TTP of unknown origin, ADAMTS13 genetic defects were found in 15 people (33%). The researchers reported 20 different ADAMTS13 variants in total, including eight novel variants, and they did not find a definitive link between specific variants and specific symptom patterns. [5]

A case series of two brothers illustrated that inherited clotting-related small blood vessel disease can look different even within one family. Whole-exome sequencing found a homozygous ADAMTS13 mutation linked to hereditary TTP and a separate homozygous CFHR1/CFHR3 deletion linked to atypical hemolytic uremic syndrome, while the brothers had different levels of kidney involvement. [6]

A separate case report described an adult man with congenital TTP who had very low ADAMTS13 activity (3.81%) and no ADAMTS13 inhibitors, with family testing supporting inherited disease. Genetic testing found three compound heterozygous ADAMTS13 mutations, including one novel pathogenic variant, underscoring that unique combinations of gene changes can underlie the same diagnosis. [7]

For patients and caregivers, this set of studies mainly adds background about why genetic testing can matter in inherited TTP: many different ADAMTS13 gene changes may be involved, and some may be newly recognized in certain regions or families. It also suggests that genetics alone may not reliably forecast which organs (such as the kidneys or brain) will be affected, especially when more than one inherited condition could be present in a family. What remains uncertain is how often specific variants lead to specific symptom patterns, because the evidence here comes from exploratory research and a small number of family cases.

These papers looked at how immune thrombotic thrombocytopenic purpura (immune TTP) treatment might be adjusted: shortening plasma exchange, using a different immune-targeting medicine for relapsed disease, and checking whether caplacizumab relates to longer-term brain effects. Overall, the results pointed toward similar short-term blood recovery with less plasma exchange in selected patients, and possible longer-term benefits or signals to study further, but the evidence remains limited by small, observational designs. [8] [9] [10]

In a comparative observational study of people with immune TTP treated with caplacizumab plus immunosuppression, an abbreviated course of therapeutic plasma exchange (TPE) did not worsen platelet count recovery or how durable that recovery was, compared with a standard TPE course that continued until a higher platelet threshold was reached for multiple days. The authors suggested that higher-quality studies are needed to confirm how to decide safe stopping points. [8]

In a small retrospective multicenter series (5 adults, 8 treatment episodes) of relapsed or refractory immune TTP, daratumumab was followed by rapid improvement of ADAMTS-13 activity (a blood enzyme that is typically very low in immune TTP) in most episodes, and several remissions lasted into long-term follow-up. Even so, relapses still occurred in most patients over time, and retreatment helped in some episodes, showing that responses may not always be permanent. Side effects reported were two mild infusion-related reactions, without severe reactions or infectious complications in this series. [9]

In an exploratory observational study of refractory immune TTP survivors (16 people) comparing standard care with or without caplacizumab, the group that received caplacizumab had higher blood-brain barrier permeability at baseline but showed a reduction in this measurement over 12 months. Higher permeability measurements were linked with worse cognitive test scores and lower ADAMTS-13 activity, suggesting a possible connection between ongoing disease-related biology and thinking or memory outcomes, but the study was small and not randomized. [10]

For patients and caregivers, these results mainly add context for conversations clinicians are already having about how to balance treatment intensity, relapse prevention, and longer-term recovery in immune TTP. The shortened plasma exchange approach and daratumumab use were supported by small, non-randomized evidence, so it is still uncertain who might benefit most and how well results generalize across different hospitals and patient situations. The brain-related study suggests that some survivors may have measurable changes linked to cognition and that caplacizumab could be connected to improvement over time, but this remains exploratory and needs confirmation in larger, more definitive studies. [8] [9] [10]

This group of papers shows that TTP can appear together with other major health conditions (like HIV infection), and that several different "small-vessel clotting" disorders can look similar at first because they share low platelets and organ strain. Overall, the research points to the importance of understanding the underlying trigger (infection, immune condition, pregnancy-related disorder, or medication exposure) because outcomes and the most useful tests can differ. Evidence ranges from moderate-strength retrospective studies to single-patient case reports, so some conclusions are more certain than others.

In a 10-year single-center cohort from South Africa, most patients with TTP were living with HIV, yet HIV status itself did not clearly change remission, relapse, or death rates in this setting. Remission occurred in 71.9% of patients, and among people with HIV, relapses were reported only in those who had defaulted antiretroviral therapy (HIV treatment). [11]

In septic shock, one ICU study grouped patients into a "TTP-like" pattern, sepsis-induced clotting problems, or controls, and found higher von Willebrand factor levels in the TTP-like and sepsis-induced clotting groups. The sepsis-induced clotting group had lower platelet lows, more liver and kidney injury, and higher 28-day death rates than the other groups, suggesting that lining-of-the-blood-vessel injury and widespread microclotting may help explain why platelets fall during severe infection. [12]

Pregnancy-related clotting disorders can also overlap with other thrombotic microangiopathies (conditions with small-vessel clots). One postpartum case described HELLP syndrome followed by atypical hemolytic uremic syndrome (aHUS) with kidney biopsy changes, along with a newly described CFHR5 gene change and lab evidence of abnormal complement activity; the patient improved with plasma infusion and supportive care. [13]

For patients and caregivers, these reports mainly add background context: TTP can occur in people who are also dealing with HIV, and some ICU or pregnancy-related clotting syndromes can resemble TTP even when the biology may be different. What remains uncertain is how well these patterns apply across hospitals and countries, and which tests best separate look-alike syndromes in real time, since several papers note limited access to specialized testing.

These papers focus on situations where TTP (or a closely related small-vessel clotting disorder) appears alongside other immune problems or after certain medications. The overall pattern is that overlap can complicate the clinical picture, and evidence is limited because it comes from a single case report and a spontaneous safety-reporting database rather than controlled studies.

One case report described a 73-year-old man diagnosed with both immune-mediated TTP and Evans syndrome (a condition involving immune attack on blood cells). His platelet count and a marker of cell breakdown improved after three days of plasma exchange plus corticosteroids, but treatment was stopped because of worsening multi-organ dysfunction, highlighting how severe overlap presentations can be. [14]

A pharmacovigilance analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) looked at blood-related side effects reported with bevacizumab in ovarian cancer. While anemia and low white blood cells were most commonly reported, rare reports included thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome, with a median reported onset of 30 days for blood toxicities overall; because FAERS is based on voluntary reports, it cannot determine true risk or confirm bevacizumab as the cause. [15]

Relatedly, another single-patient report described a 6-year-old boy with atypical hemolytic uremic syndrome (aHUS), treated with therapeutic plasma exchange after initial treatments, with remission and improved kidney and blood measures. The report also notes that key tests (like ADAMTS13 activity and genetic/complement testing) were not available, which can make it harder to distinguish between TTP and other thrombotic microangiopathies in some settings. [16]

For patients, this theme is most relevant as context about overlap and uncertainty: TTP may be discussed alongside other immune blood disorders or in the setting of cancer treatment, and some conditions can mimic each other when specialized testing is limited. The main uncertainty is frequency and causality, since one paper is a single case and the drug-safety paper is based on reports rather than confirmed, systematically collected cases.

Across these studies, living with thrombotic thrombocytopenic purpura (TTP) was linked to substantial healthcare use and costs, along with common barriers to getting ongoing care. The evidence comes from one England database study (congenital TTP) and one U.S. survey (immune TTP), so results reflect different health systems and patient groups. [17] [18]

In England, a linked healthcare-records study of 36 people with congenital TTP found many had serious health events and higher yearly healthcare costs than matched people without TTP. About 38.9% had an acute episode and 19.4% had an organ damage event, and average annual costs were GBP 6,155 versus GBP 858 in controls. [17]

In the United States, a survey of 281 adults with self-reported immune TTP described gaps in survivorship and relapse-prevention care, even though most respondents reported being under the care of a TTP specialist. More than half said relapse-prevention treatment was not discussed, and 38% reported lab monitoring every 6 months or less. [18]

The same survey also highlighted the day-to-day burden beyond medical visits, including high self-reported mental health impact and financial barriers. Many respondents reported depression or anxiety related to immune TTP, while fewer reported being referred to mental health care. Insurance coverage varied, including a group reporting no insurance. [18]

For patients and caregivers, these papers add context that TTP can affect life well after an acute episode, through ongoing healthcare needs, costs, and practical barriers like follow-up access and affordability. The England study helps quantify healthcare use and costs in congenital TTP, while the U.S. survey shows that many immune TTP survivors report unmet needs in relapse-prevention conversations, monitoring, and mental health support. What remains uncertain is how widely these results apply to all people with TTP, because one study was small and the other relied on self-reported survey responses and may not represent everyone.

Across these papers, a consistent message is that ADAMTS13 activity is strongly shaped by its shape (how the protein folds and opens) and by the environment in which it is tested. One study focuses on ADAMTS13's own built-in self-braking mechanism, while the other shows that antibodies from immune thrombotic thrombocytopenic purpura (iTTP) patients can reduce ADAMTS13 function in more than one way, and those effects can look different in different assay settings. [19] [20]

A hybrid computer simulation and laboratory study proposed a unified model for how ADAMTS13 can keep itself in a "latent" (autoinhibited) state. In this model, farther-away parts of the protein can cover up key areas needed to grab and cut its target, helping explain why ADAMTS13 can appear less active until it shifts into a more open shape. [19]

The same work suggested specific parts of ADAMTS13 help create this self-blocking state: two regions (called TSP7 and TSP8) were modeled as binding to the enzyme's working module, and another region (called L3) was modeled as acting like a "fake substrate" that sits in the active area and blocks binding sites. The authors supported this model using lab measurements that included how certain monoclonal antibodies bind and how ADAMTS13 changes under different conditions like pH changes or EDTA. [19]

An in vitro study using full-length IgG1 and IgG4 anti-ADAMTS13 antibodies from iTTP patients found that antibody-driven inhibition depended on the test environment. Under routine diagnostic-type conditions, antibodies more strongly disrupted ADAMTS13's ability to recognize its target, while under more physiologic conditions they more strongly reduced the enzyme's catalytic turnover (its ability to perform the cutting reaction). [20]

This antibody study also reported that different patient samples behaved differently, including mixtures of stimulatory and inhibitory effects when multiple antibody types were present. It also noted that low measured ADAMTS13 antigen did not fully explain the activity patterns, suggesting mechanisms beyond simply removing ADAMTS13 from the blood. [20]

For patients and caregivers, these are background biology studies that help explain why ADAMTS13 can look more or less active depending on how it is measured, and why antibody effects may not be identical from one person to another. They do not change how iTTP is diagnosed or treated by themselves, but they may guide future work on better tests that reflect what ADAMTS13 is doing in the body and on understanding different antibody behaviors. Important uncertainties remain because both studies were preclinical (lab and modeling) rather than studies tracking patient outcomes.