Isolated distal deep vein thrombosis is a peculiar clinical entity. Unlike proximal deep vein thrombosis, which forms in the larger veins of the thigh and pelvis and carries a well-recognized risk of life-threatening pulmonary embolism, IDDVT is confined to the infrapopliteal veins below the knee. It has historically been regarded as relatively benign, yet modern registry data show a heterogeneous course: some clots resolve quietly, while others extend proximally, recur, or seed the lungs, particularly when left untreated. Because IDDVT is more often triggered by transient insults such as surgery or trauma rather than chronic systemic hypercoagulability, the evidence base built on non-surgical populations may simply not transfer to the postoperative ward. That gap is precisely where the new study positions itself.

The clinical dilemma is acute. Current guidelines generally recommend at least three months of anticoagulation for high-risk IDDVT, favoring direct oral anticoagulants such as rivaroxaban. But those recommendations rest largely on randomized trials that excluded patients at high risk of postoperative bleeding. Surgeons and physicians facing a fresh surgical wound in a hypervascular abdominopelvic field often hesitate to deploy full-dose anticoagulation, and real-world practice frequently drifts toward more conservative dosing. Whether that drift protects patients or leaves them under-protected against clot propagation has been unknown. The Dalian team, led by Hansheng Bai and senior authors Guangjun Fan and Si Wu, set out to quantify that trade-off using more than a decade of real-world data.

The researchers screened 302 patients who developed IDDVT after urological surgery at the Second Hospital of Dalian Medical University between January 2013 and April 2025. After exclusions for incomplete follow-up, pre-existing proximal clots, significant bleeding, or other indications for anticoagulation, 247 patients formed the initial cohort. Because dose selection in routine practice was made by treating physicians rather than by protocol, the investigators used propensity score matching to construct balanced comparison groups, pairing each patient on the 10-milligram regimen with a statistically similar patient on the 20-milligram regimen. The matching model incorporated an unusually thoughtful variable: the surgical approach itself, dichotomized as endoscopic procedures performed through natural orifices versus major structural surgeries involving abdominal or retroperitoneal dissection, as a surrogate for surgical trauma and bleeding risk. Year of surgery was also included to absorb temporal shifts in practice across the twelve-year window.

After matching, 152 patients remained, 76 in each arm. The groups were well balanced on age, body mass index, platelet count, D-dimer levels, comorbidities such as hypertension and diabetes, malignancy history, and the distribution of surgical approaches. The median time from surgery to clot diagnosis was one to two days, and anticoagulation typically began about three days later. Most patients completed three months of therapy, with a minority extended to six months when ultrasound failed to show resolution. The stage was thus set for a head-to-head comparison of two intensities of the same drug in a genuinely perioperative population.

The primary outcome was thrombus progression to proximal deep vein thrombosis or pulmonary embolism, analyzed with Fine–Gray competing-risk models that treated bleeding-related treatment discontinuation as a competing event. The cumulative incidence of progression at the end of follow-up was 11.84 percent in the low-dose group and 9.21 percent in the standard-dose group, a difference that was not statistically significant. The subdistribution hazard ratio of 1.29 came with a 95 percent confidence interval stretching from 0.48 to 3.46, and a P value of 0.613. Thrombus resolution told a similar story: roughly two-thirds of patients in each group achieved complete disappearance of the clot on follow-up ultrasound, with no significant difference between regimens.

Bleeding was where the regimens decisively parted ways. Clinically relevant non-major bleeding, classified according to International Society on Thrombosis and Haemostasis criteria, occurred in 6.58 percent of the low-dose group versus 19.74 percent of the standard-dose group, yielding a hazard ratio of 0.31 with a confidence interval of 0.11 to 0.85 and a P value of 0.023. The pattern was echoed in early hematuria: within the first month of treatment, dipstick-positive blood in the urine appeared in 23 patients on the standard dose compared with 12 on the low dose, a statistically significant difference. Bleeding also disrupted care far more often under full dosing, interrupting treatment in 19.74 percent of standard-dose patients versus 6.58 percent of low-dose patients. In a population where even macroscopic hematuria can force a dose reduction or outright discontinuation, that interruption burden is not a trivial footnote; it strikes directly at treatment continuity, the very mechanism by which anticoagulation fails to protect.

The authors are careful, almost emphatic, about what these results do not show. A wide confidence interval around the progression estimate, a modest sample size, nonrandomized treatment allocation, and the ever-present possibility of residual confounding mean the study cannot claim the two doses are equivalent in antithrombotic efficacy. Physicians may have preferentially prescribed lower doses to frailer patients, a classic confounding-by-indication problem that propensity matching can soften but never eliminate. Patients with significant renal impairment were excluded, limiting generalizability to older surgical patients, and follow-up ultrasound timing was not standardized, opening the door to surveillance bias. The findings are framed as hypothesis-generating rather than practice-changing, and the authors explicitly call for randomized non-inferiority trials to settle the question.

Nevertheless, the study lands in a converging evidence landscape. The EINSTEIN-CHOICE trial demonstrated that low-dose rivaroxaban can sustain antithrombotic protection during extended treatment in the broader venous thromboembolism population, and smaller studies in critically ill patients and in post-thoracic surgery IDDVT have reported comparable thrombotic outcomes with reduced dosing. A separate study of different rivaroxaban doses in IDDVT observed a significantly elevated bleeding risk with standard dosing, mirroring the Dalian results. Registry analyses add nuance: the RIETE registry has shown that concomitant superficial vein thrombosis raises pulmonary embolism risk, that cancer-associated IDDVT carries higher recurrence and bleeding risks, and, intriguingly, that low LDL cholesterol predicts anticoagulation-related bleeding, hinting that laboratory markers could one day sharpen individualized dosing decisions.

The pathophysiological logic is also coherent. Distal clots carry a smaller thrombus burden and lower rates of proximal extension than proximal thrombi, and when the dominant trigger is a transient surgical insult rather than systemic hypercoagulability, local factors may drive thrombosis more than circulating coagulation drive. In that setting, a full maintenance dose may deliver more bleeding than benefit during the early postoperative window when wounds are still healing. If randomized trials confirm the pattern seen here, the implications would ripple across surgical specialties: a cheaper, better-tolerated regimen that keeps patients on therapy instead of interrupting it, and a template for dose de-escalation in other high-bleeding-risk perioperative scenarios. For now, the message is one of cautious possibility, a signal that in the contest between clot and bleed after surgery, less anticoagulation may sometimes be exactly enough.

Subject of Research: Low-dose versus standard-dose rivaroxaban for postoperative isolated distal deep vein thrombosis

Article Title: De-escalated rivaroxaban in postoperative isolated distal deep vein thrombosis: a propensity score–matched study

Article References: Bai, H., Tang, Q., Jin, L., Yang, M., Fan, G., & Wu, S. (2026). De-escalated rivaroxaban in postoperative isolated distal deep vein thrombosis: a propensity score–matched study. Frontiers in Cardiovascular Medicine, 13, 1855986. https://doi.org/10.3389/fcvm.2026.1855986

Image Credits: AI Generated

DOI: 10.3389/fcvm.2026.1855986

Keywords: rivaroxaban, anticoagulation, deep vein thrombosis, isolated distal DVT, postoperative complications, bleeding risk, direct oral anticoagulants, propensity score matching, urological surgery, venous thromboembolism, dose de-escalation, thrombosis

Antithrombotic treatments, which include antiplatelet drugs such as aspirin and clopidogrel as well as anticoagulants like low-molecular-weight heparin, warfarin, and direct oral anticoagulants, are remarkably common in specialized palliative cancer care. Clinical guidelines suggest that most patients with cancer who develop thrombosis benefit from long-term antithrombotic treatment, regardless of adverse effects. Yet the research team behind the new study had previously shown, in a retrospective analysis of palliative care patients, that the risk of bleeding in patients using antithrombotics during the last year of life was high, independent of age, indication, and type of antithrombotic, while the risk of thrombosis after deprescribing was very low. Intriguingly, that earlier work also revealed that patients with advanced prostate cancer had a significantly increased risk of bleeding compared to patients with other cancer types and non-cancer diagnoses. The primary aim of the present study was therefore to dig deeper into what makes men with prostate cancer on antithrombotics especially prone to bleeding.

The study was designed as a retrospective single-center cohort investigation, in which the researchers reviewed medical records for all deceased patients who had been admitted to ASIH Stockholm Södra, a Stockholm palliative care unit providing both specialized home care and in-patient specialized palliative care, from January 1, 2016, until December 31, 2018. The original cohort had screened all admitted patients for use of antithrombotics, classified under ATC code B01, during the last year of life, excluding patients with prophylactic antithrombotic treatment after surgery. For this sub-study, the researchers extracted all patients with prostate cancer, both with and without antithrombotic treatment, from the original cohort. The study was approved by the Swedish Ethical Review Board.

The resulting cohort consisted of 100 men with prostate cancer, of whom 64, or 64 percent, were treated with antithrombotics during the last year of life. The mean age at death was 79.1 years. The most common antithrombotic treatment was low-molecular-weight heparin, used by 31 patients, or 48.4 percent, followed by antiplatelet drugs in 27 patients, or 42.2 percent. Only 6 patients, or 9.4 percent, had other oral drugs such as warfarin or direct oral anticoagulants. Prophylaxis and atrial fibrillation were the most common indications for antithrombotic treatment, with prophylaxis defined as cases where no clear indication could be found in the medical records.

Among those treated with antithrombotics, 24 patients, or 37.5 percent, experienced clinically significant bleeding during their final year. The most common source of bleeding was hematuria, blood in the urine, which affected 12 patients, followed by nasal bleeding and bleeding from the skin, each affecting four patients. One patient suffered a central nervous system bleed. In the entire cohort, 36 men with prostate cancer had no treatment with antithrombotics, and eight of these men, or 22.2 percent, experienced some form of bleeding, most commonly hematuria followed by nasal bleeding. Perhaps surprisingly, there was no statistically significant difference in the risk of bleeding between those treated with antithrombotics and those not treated, with a relative risk of 0.59 and a 95 percent confidence interval of 0.29 to 1.23, and a p-value of 0.12. The researchers caution that this might be due to lack of power in the limited cohort, but their data do not support a clear increase in bleeding risk attributable to antithrombotics alone.

To identify clinical markers of vulnerability, the researchers used log-binomial generalized linear models to calculate relative risks and 95 percent confidence intervals for each variable potentially related to bleeding, including age, indication for antithrombotics, and treatment with steroids or non-steroidal anti-inflammatory drugs. Factors associated with increased risk of bleeding were the need for blood transfusion during the last year of life, with a relative risk of 3.15 and a 95 percent confidence interval of 1.34 to 7.39, and low thrombocyte count, defined as fewer than 50 times 10 to the ninth per liter, with a relative risk of 2.41 and a 95 percent confidence interval of 1.39 to 4.16. In addition, patients receiving antithrombotics for deep vein thrombosis treatment had a higher risk of bleeding compared to those on prophylactic treatment, with a relative risk of 2.44 and a 95 percent confidence interval of 1.21 to 4.94. Notably, age, type of antithrombotic, and use of steroids or NSAIDs were not associated with increased bleeding risk.

The relationship between blood transfusion and bleeding is probably one of reverse causality, the researchers explain, since bleeding or bone marrow failure might occur before the transfusions. Nevertheless, transfusion need might serve as a practical marker for when antithrombotic treatment should be evaluated. Earlier studies show that high rates of significant bone marrow failure, including anemia and thrombocytopenia, in treatment-refractory patients with prostate cancer predict an unfavorable prognosis, which is in concordance with the new results showing that low thrombocyte count was associated with a high risk of bleeding. Thus, when thrombocytopenia occurs, it might be time to evaluate whether antithrombotic treatment should continue. Hematuria, which is well established as common in prostate cancer, was also the most common source of bleeding in this study, and could be one explanation for the high bleeding risk in men with prostate cancer compared to patients with other diagnoses. Previous work by Ajabnoor and colleagues has shown that men with prostate cancer and atrial fibrillation generally have an increased risk for bleeding, in line with the team’s earlier findings.

The study also examined the effects and timing of deprescribing antithrombotics, with striking results. No patients developed any cardiovascular complications, such as myocardial infarction, stroke, or systemic embolism, after deprescribing antithrombotics during the last year of life. For 32 patients, or 50 percent, antithrombotics continued until the last days of life and were deprescribed zero to six days before death. Antithrombotics were not deprescribed at all for 14 patients, or 22 percent. For those who continued treatment until the very last days, approximately 43 percent received it orally, though it is not known whether they were able to swallow the medication, as most patients cannot take oral medications during the last days of life.

The incidence of bleeding in the present study, at 37.5 percent of all men with prostate cancer treated with antithrombotics, is higher than in earlier studies, including the team’s original study where the incidence was 16.1 percent in all patients treated with antithrombotics, and a French study by Tardy and colleagues where the incidence of clinically relevant bleeding was 9.8 percent. However, those studies included palliative care patients with all kinds of diagnoses, not only men with prostate cancer, which may partly explain the difference. To their knowledge, the researchers note, this is the first study to evaluate clinical markers for vulnerability to bleeding in men with prostate cancer and treatment with antithrombotics in palliative care.

The study has several limitations that warrant careful interpretation. First, the sample size was small, which may affect the results in terms of power, and the effect estimates should be interpreted with caution, since the confidence intervals are wide and there is high potential for both type I and type II errors. Second, the study is based on retrospective data, and confounding factors and reverse causality might be present, so no causal relationships can be drawn. Due to the small sample size and retrospective, non-interventional design, no firm conclusions about safety after deprescribing can be drawn, which needs to be evaluated in a future prospective study. Moreover, laboratory values were obtained up to six months before death and may not reflect the status at the time of bleeding, a potential source of misclassification. Hematuria is also common in patients with prostate cancer regardless of whether they are treated with antithrombotics or not. Finally, the results are based on data from a single Swedish specialized palliative care unit, so they may not be generalized to other healthcare systems or less advanced care settings. Still, the researchers conclude that given the increased risk of bleeding and the often limited life expectancy of these patients, the potential benefits of preventing thromboembolic events must be weighed against the potential harms of antithrombotic treatment in each case, with clinical markers such as low thrombocyte count and need for transfusions offering clinicians concrete signposts for when that evaluation should begin.

Subject of Research: Clinical Markers of Vulnerability for Bleeding in Men With Prostate Cancer and Antithrombotic Treatment

Article Title: Clinical Markers of Vulnerability for Bleeding in Men With Prostate Cancer and Antithrombotic Treatment

Article References: Björkhem‐Bergman, L., Hedman, C., Szilcz, M., & Frisk, G. (2026). Clinical Markers of Vulnerability for Bleeding in Men With Prostate Cancer and Antithrombotic Treatment. Cancer Reports, 9(10), Article e70720. https://doi.org/10.1002/cnr2.70720

Image Credits: AI Generated

DOI: 10.1002/cnr2.70720

Keywords: palliative care, prostate cancer, antithrombotics, bleeding risk, thrombocytopenia, deprescribing, end-of-life care, Cancer Reports, Clinical, Markers, Vulnerability, Bleeding

The conclusion matters because older adults are precisely the population in which any chemopreventive effect would be most valuable. Cancer incidence rises steeply with age, and the majority of cancer diagnoses in high-income countries occur in people over 65. If a safe, inexpensive, widely available medication could meaningfully blunt that risk, the public health implications would be enormous. The new summary, formatted as a Bottom Line Summary intended to distill evidence for practicing clinicians, cuts against that hope. Its patient-facing message is blunt: for those age 65 and older, taking a low dose aspirin every day does not lower cancer risk.

To understand why the field arrived at this point, it helps to trace the arc of the aspirin hypothesis. Aspirin, or acetylsalicylic acid, works by irreversibly inhibiting cyclooxygenase enzymes, thereby suppressing production of prostaglandins and thromboxane. That mechanism explains its classic effects on pain, fever, inflammation, and platelet aggregation, and it also supplied a plausible biological route to cancer prevention. Chronic inflammation is a recognized contributor to tumor development, and prostaglandin signaling has been implicated in processes ranging from cell proliferation to angiogenesis. Epidemiologists observed that people who took aspirin regularly appeared to have lower rates of colorectal cancer in particular, and randomized trials designed to test aspirin for cardiovascular prevention began to report, on longer follow-up, apparent reductions in cancer incidence and mortality among those assigned to the drug.

That evidence base, however, was never as clean as the headlines suggested. The randomized trials that generated the most optimistic findings were generally designed and powered to detect cardiovascular events, not cancer, and their cancer results emerged from post hoc analyses with varying durations of follow-up. Observational studies, for their part, are vulnerable to confounding: people who take aspirin regularly differ in many ways from people who do not, including in health-seeking behavior, access to care, and screening rates. When the evidence was assembled systematically, the signal weakened. A 2020 updated systematic review and subgroup meta-analysis of 29 randomized clinical trials of long-term aspirin use for primary cancer prevention, cited in the new summary, examined the totality of trial data and found that the hoped-for protective effect was not consistently supported across cancer types, populations, and doses.

Large randomized trials provided some of the most decisive tests. The ASCEND study, published in the New England Journal of Medicine in 2018, randomized more than 15,000 people with diabetes to aspirin or placebo and found that while aspirin reduced serious vascular events, it also increased major bleeding, and it did not produce the kind of broad benefit that would justify routine use. The JPAD trial in Japanese patients with type 2 diabetes and its ten-year observational follow-up, also published in 2018, examined aspirin’s effects in a diabetic population and found no evidence of a cancer chemopreventive benefit. These trials, conducted in populations at elevated vascular risk who might have been expected to benefit most, consistently failed to demonstrate that low-dose aspirin prevents cancer, while repeatedly confirming its capacity to cause bleeding.

The bleeding issue is central to any risk-benefit calculation. Aspirin’s inhibition of platelet function is permanent for the lifespan of each platelet, and because platelets circulate for roughly a week to ten days, even low doses produce a sustained anti-hemostatic effect. In younger and middle-aged adults this translates into a modest but real excess of gastrointestinal hemorrhage and, less commonly, hemorrhagic stroke. In older adults the risk is amplified: age-related changes in the gastric mucosa, higher prevalence of Helicobacter pylori infection and other comorbidities, greater use of interacting medications such as anticoagulants and nonsteroidal anti-inflammatory drugs, and increased frailty all raise the likelihood that bleeding will be serious rather than merely inconvenient. A prevention strategy that offers no cancer benefit while adding bleeding risk to a 75-year-old is, on its face, difficult to defend.

Professional bodies have been moving in this direction for several years. In the United States, the Preventive Services Task Force in recent guidance narrowed its recommendation on aspirin for primary cardiovascular prevention, declining to recommend initiation in adults 60 and older and suggesting that any decision to start aspirin in adults 40 to 59 at high cardiovascular risk should be individualized. The cancer-prevention rationale, once a secondary argument in favor of aspirin, has largely fallen away as trial evidence accumulated. The new Bottom Line Summary consolidates that shift for the specific question of cancer prevention in older adults, aligning clinical guidance with the randomized evidence rather than with the earlier observational enthusiasm.

The summary also illustrates the value of the evidence-based medicine approach it represents. Rather than relying on mechanistic plausibility or on the accumulated weight of observational associations, Burke and Wheeler, with the SGIM Evidence-Based Medicine Task Force, distilled the randomized trial evidence into a single actionable conclusion. The authors report no funding related to the submission and no conflicts of interest, and the work was reviewed through the SGIM EBM Subcommittee. In a field where enthusiasm for a cheap intervention can outpace the data, such structured syntheses serve as a corrective, translating complex and sometimes contradictory trial literature into guidance that a busy primary care clinician can apply directly in the examination room.

For patients, the practical takeaway is straightforward. People aged 65 and older should not start taking daily low-dose aspirin with the expectation of preventing cancer, and those who are taking it for that purpose have grounds to discuss stopping with their physician. Aspirin retains clear, well-established roles, including in the treatment of pain and fever and in the secondary prevention of cardiovascular events in people who have already had a heart attack or ischemic stroke, where its benefits demonstrably outweigh its risks. What the accumulating evidence has removed is the justification for aspirin as a general-purpose preventive pill in healthy older people. The once-promising idea that a daily tablet could ward off both heart attacks and cancer has, for the older population, been narrowed by the data: the cancer-prevention half of that promise has not survived rigorous testing, and the decision to take aspirin should rest on individualized assessment of cardiovascular benefit against bleeding risk, not on the hope of avoiding a cancer diagnosis.

Subject of Research: Low-dose aspirin for primary cancer prevention in older adults

Article Title: EBM BLS: Low Dose Aspirin Does Not Reduce the Risk of Cancer in Older Adults

Article References: Burke, H. B., & Wheeler, S. G. (2026). EBM BLS: Low Dose Aspirin Does Not Reduce the Risk of Cancer in Older Adults. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-026-10876-8

Image Credits: AI Generated

DOI: 10.1007/s11606-026-10876-8

Keywords: aspirin, cancer prevention, chemoprevention, older adults, geriatrics, primary prevention, evidence-based medicine, randomized trials, bleeding risk, Journal of General Internal Medicine, ASCEND trial, risk-benefit

The letter, authored by Barina Khan of Karachi Medical and Dental College and published on 3 September 2026 as Volume 29, article number 59 of the journal, is written in direct response to a pilot study by Tran and colleagues that documented dynamic platelet dysfunction in patients undergoing extracorporeal membrane oxygenation. That pilot work, which appeared in the same journal earlier in 2026, used platelet function testing to follow how platelet performance changed over the course of ECMO support and explored whether those changes tracked with clinically significant bleeding. The new letter does not dispute that platelet dysfunction is real and important in ECMO patients. Instead, it questions whether the specific instrument and protocol used can reliably detect it in this population.

The core of the concern lies in what laboratory scientists call a ceiling effect. The PFA-200 measures the time it takes for platelets, under controlled high shear conditions, to form a plug that occludes a microscopic aperture in a cartridge coated with platelet agonists such as collagen and epinephrine or collagen and adenosine diphosphate. When platelet function is severely impaired, the plug simply never forms, and the instrument reports a result at or above the maximum assay limit, typically a value greater than 300 seconds. In profoundly thrombocytopenic or platelet-exhausted patients, which many ECMO patients quickly become, large numbers of test results pile up at this artificial ceiling. Once a value has been censored at the upper limit, the assay can no longer distinguish between moderately severe and catastrophic platelet failure, compressing exactly the range of dysfunction that matters most for predicting bleeding.

Khan’s letter argues that this censoring problem is particularly acute during ECMO, where platelet counts fall progressively, platelets become activated and exhausted through continuous contact with the oxygenator membrane and circuit tubing, and acquired platelet defects accumulate over days of support. If a study correlates closure times with bleeding episodes in such a cohort, the relationship may be flattened or distorted by the many results that read simply as greater than 300 seconds. Statistical associations computed on censored data risk either underestimating the true strength of the link between platelet failure and hemorrhage or, depending on how the ceiling values are handled in the analysis, producing misleading conclusions about when platelet dysfunction begins to matter clinically.

The second confounder the letter highlights is hematocrit, the proportion of blood volume occupied by red blood cells. It is a long-standing observation in hematology that the PFA-100 and PFA-200 are exquisitely sensitive to the hematocrit of the sample. Red cells are not passive bystanders in primary hemostasis; they physically push platelets toward the vessel wall in flowing blood and contribute chemical signals, including adenosine diphosphate released from erythrocytes, that amplify platelet activation. When the hematocrit drops below roughly 30 percent, closure times lengthen even if platelets themselves are functioning normally, and severe anemia can push closure times beyond the assay limit on its own. Conversely, elevating the hematocrit can shorten closure times and mask genuine platelet defects, an effect documented decades ago in studies of uremic and cirrhotic patients evaluated on the platelet function analyzer.

This sensitivity is a serious problem in the ECMO population specifically. Patients on extracorporeal support are frequently anemic, whether from hemodilution caused by circuit priming, hemolysis within the circuit, repeated blood sampling, gastrointestinal bleeding, or the suppressed red cell production that accompanies critical illness. In such patients, a prolonged closure time may reflect the red cell deficit rather than intrinsic platelet failure, and the degree of prolongation may bear little relationship to the true functional capacity of the platelets. Khan’s letter suggests that unless hematocrit is either matched across study groups or formally adjusted for in the statistical model, the association reported between PFA-200 closure times and bleeding in ECMO patients may be confounded from the outset, with anemia masquerading as platelet dysfunction.

The letter places these concerns in a broader and somewhat sobering context. The clinical utility of closure times on the platelet function analyzer has been debated for more than two decades. Studies in cardiac surgery patients have repeatedly questioned whether the device predicts blood loss after cardiopulmonary bypass, another setting in which acquired platelet defects, hemodilution and anemia coexist. A comprehensive review in the American Journal of Hematology catalogued the assay’s utility across bleeding disorders while also documenting its susceptibility to hematologic variables, and a worldwide survey of platelet function testing practices conducted under the auspices of the International Society on Thrombosis and Haemostasis underscored how much variability exists in how platelet function is assessed even among expert laboratories. Against that backdrop, applying the PFA-200 to the uniquely harsh environment of extracorporeal circulation demands particular caution about the assay’s known limitations.

None of this means the assay should be abandoned in the ECMO setting, the letter’s argument implies, but rather that its results must be interpreted with an awareness of when the instrument can and cannot see. Practical strategies exist. Researchers can report the proportion of censored results explicitly and use statistical methods designed for data with detection limits rather than treating the ceiling value as a genuine number. Studies can stratify closure times by hematocrit, exclude samples with severe anemia from platelet-focused analyses, or measure closure times only after red cell transfusion has stabilized the hematocrit. Complementary tests that are less dependent on shear, hematocrit and sample handling, such as light transmission aggregometry, flow cytometric markers of platelet activation, or other point-of-care viscoelastic and platelet-mapping devices, can help triangulate the true state of platelet function. The pilot study’s central observation, that platelet dysfunction evolves dynamically during ECMO, remains valuable; the question is whether the PFA-200, as deployed, is measuring that dysfunction or partly measuring the anemia around it.

The stakes are far from academic. Bleeding remains one of the most feared complications of ECMO, occurring in a substantial fraction of patients and driving decisions about anticoagulation intensity, transfusion thresholds and circuit management. If closure times on the PFA-200 are adopted as a bedside guide without accounting for ceiling effects and hematocrit, clinicians risk both false reassurance, when an apparently normal result is actually capped by the assay limit in a patient with profound platelet exhaustion, and false alarm, when a prolonged result in an anemic patient triggers unnecessary platelet transfusion. Given that platelet transfusions carry their own risks, including allergic reactions, transfusion-associated circulatory overload and the theoretical promotion of thrombosis in a patient group already prone to circuit clotting, refining which patients truly need platelet support is a matter of real clinical consequence.

Khan’s letter is a compact methodological intervention, but it lands at a moment when interest in platelet function testing during extracorporeal support is growing rapidly. As devices for measuring closure times, aggregometry and platelet activation migrate from hematology laboratories to the intensive care unit bedside, the letter serves as a reminder that the validity of any such measurement depends on the biology of the sample as much as the precision of the instrument. In ECMO patients, where thrombocytopenia, platelet exhaustion and anemia march together, closure times must be read with both eyes open. Whether future studies can confirm a robust, hematocrit-independent association between PFA-200 results and bleeding in this population will determine whether the assay earns a genuine place in the ECMO management toolkit, or remains a test whose ceiling it cannot see above and whose red cell context it cannot escape.

Subject of Research: The reliability of PFA-200 platelet function closure times for assessing bleeding risk during extracorporeal membrane oxygenation

Article Title: PFA-200 closure times in ECMO: Are ceiling effects and hematocrit confounding the bleeding association?

Article References: Khan, B. (2026). PFA-200 closure times in ECMO: Are ceiling effects and hematocrit confounding the bleeding association?. Journal of Artificial Organs, 29(4), Article 59. https://doi.org/10.1007/s10047-026-01589-0

Image Credits: AI Generated

DOI: 10.1007/s10047-026-01589-0

Keywords: ECMO, PFA-200, platelet function, closure time, bleeding risk, hematocrit, coagulation, extracorporeal membrane oxygenation, platelet dysfunction, anemia, point-of-care testing, Journal of Artificial Organs