Newer direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, and dabigatran offer predictable pharmacokinetics and no routine coagulation monitoring, but both classes carry bleeding risk. A knowledge test that could serve both populations, in the patient's own language and dialect, was the study's central goal. The adaptation followed two internationally recognized frameworks: the ISPOR Task Force's Principles of Good Practice for translating patient-reported outcome measures and the COSMIN taxonomy for health measurement instruments.

Two native Arabic speakers translated the 28-item tool independently, a third blinded translator translated it back into English, and the team reconciled discrepancies to secure conceptual equivalence. A panel of ten cardiovascular and anticoagulation specialists then rated every item for relevance on a five-point scale. A pilot with ten patients refined the language further, producing a mean clarity score of 4.44 out of 5, with roughly ninety percent of items rated clear or very clear.

The revisions were mostly dialectal: Iraqi Arabic handles idioms about diet and bleeding symptoms differently from Modern Standard Arabic, and the team adjusted phrasing so the questions resonated with local vernacular. The validation cohort then enrolled 280 adult outpatients at the Ibn Al-Bitar Center for Cardiac Surgery in Baghdad between mid-October and mid-December 2025, split evenly between 140 warfarin users and 140 DOAC users, matching the recommended ten participants per questionnaire item. Mean age was 54.5 years, with DOAC patients significantly older on average than warfarin patients.

Education levels also differed between the groups, a detail that would prove central to the findings. That central finding is stark: educational attainment was the only sociodemographic variable that significantly predicted knowledge scores in both cohorts. Among DOAC patients, one-way ANOVA yielded p = 0.003 for education; among warfarin patients, p = 0.006.

Patients with college or higher education scored highest (11.00 and 16.65 mean points respectively), while illiterate patients and those with only primary schooling occupied the lowest strata. Sex, age group, and even duration of therapy showed no significant association with knowledge in either group. Neither warfarin nor DOAC users showed any measurable improvement in pharmacological understanding as a function of how long they had been on therapy.

The assumption that patients gradually absorb knowledge through repeated clinic visits and prescription refills does not survive contact with this data. Knowledge of oral anticoagulation, the authors argue, is not acquired passively; it requires active, structured, health-literacy-appropriate education, which points directly at pharmacist-led counseling programs as the intervention of choice. The psychometric structure of the tool turned out to be more intricate than a single reliability number can capture.

For DOAC patients, the 20-item general scale showed acceptable internal consistency with Cronbach's alpha of 0.700. For warfarin patients, the full 28-item scale aggregated to a poor alpha of 0.512 — but that headline number conceals excellent domain-level reliability. Principal component analysis with varimax rotation extracted ten components explaining 75.44 percent of total variance, and the five items covering warfarin-specific INR knowledge loaded between 0.832 and 0.981 on a single factor with an alpha of 0.972.

Bleeding-safety items and healthcare-communication items formed further coherent, independently reliable clusters. The DOAC cohort yielded eight components explaining 70.17 percent of variance, led by a strong adverse-effects-and-bleeding factor with loadings up to 0.935. This pattern makes sense once anticoagulation knowledge is treated as what psychometricians call a formative index rather than a reflective scale.

In a reflective model, all items are driven by one underlying trait and should correlate; in a formative index, distinct factual elements — INR targets, missed-dose protocols, dietary interactions — combine to build the construct, and there is no theoretical reason they must covary. The low global alpha for the warfarin scale is therefore not a failure of the tool but a description of how fragmented real-world medication knowledge actually is, and it is precisely this fragmentation that lets the instrument triage education toward specific deficits. The cross-sectional design cannot track how knowledge evolves, predictive validity against clinical outcomes such as time in therapeutic range or bleeding events was not assessed, and recruitment at a specialized tertiary center in Baghdad may overestimate knowledge relative to resource-constrained rural clinics.

The Iraqi-dialect tuning, while a strength locally, may need cognitive debriefing before use in other Arab countries.

Subject of Research: Cultural adaptation and psychometric validation of the Oral Anticoagulation Knowledge Tool for Arabic-speaking Iraqi patients

Article Title: Cultural adaptation and validation of the Oral Anticoagulation Knowledge Tool in Arabic-speaking Iraqi patients

Article References: Al-Jailawi, Y. T. S., Al-Metwali, B. Z., & Ouj, R. H. (2026). Cultural adaptation and validation of the Oral Anticoagulation Knowledge Tool in Arabic-speaking Iraqi patients. Pharmacia, 73, Article e197938. https://doi.org/10.3897/pharmacia.73.e197938

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e197938

Keywords: oral anticoagulants, warfarin, DOACs, patient knowledge, psychometric validation, cross-cultural adaptation, Iraq, health literacy, INR monitoring, Cronbach's alpha, principal component analysis, clinical pharmacy

The clinical logic behind the trial rests on a fundamental tension in pediatric cardiology. Warfarin, a vitamin K antagonist, works by interfering with the liver’s production of several clotting factors, and its effect is measured through the international normalized ratio, or INR, a laboratory value that must be kept within a narrow therapeutic window. Too low, and clots can form on the replacement valve; too high, and bleeding becomes a serious risk. In children, this balancing act is complicated by growth spurts, dietary variability, intercurrent illness, and drug interactions, all of which can send INR values swinging unpredictably. Frequent blood draws, often from veins that are small and difficult to access, add a physical and emotional burden that families know all too well. Rivaroxaban, by contrast, directly inhibits Factor Xa, a key enzyme in the coagulation cascade, and produces a more predictable anticoagulant effect at fixed doses without routine monitoring. Pediatric dosing guidelines, such as those developed at the Mayo Clinic, have made it increasingly feasible to use the drug in younger populations, but its role specifically after pulmonary valve replacement had never been formally tested.

To fill that gap, the research team led by Mohammad Reza Sabri and colleagues at the Pediatric Cardiovascular Research Center of Isfahan University of Medical Sciences designed a randomized, double-blind clinical trial. They enrolled 44 patients over the age of five, with the youngest participant being nine years old, all of whom had undergone pulmonary valve replacement at the referral center. The investigators deliberately excluded patients with a history of thrombosis, paradoxical embolism, or reduced ejection fraction, as well as anyone with hypersensitivity to the study medications, to create a well-defined study population. Participants were randomly assigned to receive either warfarin at a dose of 0.1 to 0.3 milligrams per kilogram per day, adjusted according to INR monitoring, or rivaroxaban dosed according to the Mayo Clinic pediatric guidelines. The trial was registered in the Iranian Registry of Clinical Trials under identifier IRCT20220516054868N2, and the protocol received ethics approval in accordance with the Declaration of Helsinki, with written informed consent obtained from adult participants and from parents or guardians of minors, along with age-appropriate assent from the children themselves.

Follow-up lasted a mean of approximately six months, during which patients were assessed for both thromboembolic complications, such as valve thrombosis, stroke, or pulmonary embolism, and hemorrhagic events, ranging from minor bruising to clinically significant bleeding. Three patients were lost to follow-up, leaving 41 participants in the final analysis: 22 in the warfarin group and 19 in the rivaroxaban group. The baseline characteristics of the two groups were broadly similar, with one notable exception: body weight was significantly higher in the rivaroxaban group, a difference the authors reported with a p value of 0.044. This kind of imbalance is an inherent hazard of small randomized trials, and while it does not undermine the central findings, it is the sort of detail that clinicians reading the study will weigh when interpreting how the results might generalize to their own patients.

The headline efficacy result was unambiguous. Across roughly six months of follow-up, no thromboembolic or cerebrovascular events occurred in either treatment arm. In a trial of this size, the absence of events cannot statistically prove that the two drugs are identical in their protective effect, but it establishes that rivaroxaban kept the replacement valves clot-free in every patient studied, matching warfarin’s performance over the observation period. For a condition in which even a single valve thrombosis can be catastrophic, that finding carries real weight. It also aligns with a broader trend in pediatric hematology and cardiology, where direct oral anticoagulants have been steadily earning a place in the prevention and treatment of venous thromboembolism in children, backed by pharmacokinetic studies and dedicated pediatric trials in other clinical settings.

The safety picture was similarly reassuring, with one instructive exception. A single patient in the warfarin group, representing 4.54 percent of that arm, developed hemoptysis, the coughing up of blood that is always an alarming symptom in a young patient. On investigation, the bleeding was attributed not to the anticoagulant effect itself in a straightforward sense but to an underlying arteriovenous malformation, an abnormal tangle of vessels that can bleed when anticoagulated. When the patient was switched to rivaroxaban, the hemoptysis resolved. The episode illustrates a practical reality of anticoagulation medicine: the drug is only one variable in a complex hemostatic system, and individual anatomy can transform a standard therapy into a hazardous one. It also hints, cautiously, that switching agents may sometimes solve a bleeding problem, though a single case cannot establish that rivaroxaban is inherently safer in such situations.

Where the trial produced its most dramatic statistical separation was in patient satisfaction, measured on a ten-point scale. Patients taking rivaroxaban rated their anticoagulation experience at a mean of 8.26 with a standard deviation of 1.99, while those on warfarin averaged just 5.14 with a standard deviation of 1.09, a difference the authors reported as highly significant with a p value below 0.001. The gap is easy to explain in human terms. Warfarin demands regular blood tests to check INR, careful attention to vitamin K intake from leafy greens, vigilance about interactions with common medications including non-steroidal anti-inflammatory drugs, and dose adjustments that can feel arbitrary and anxiety-inducing. Rivaroxaban requires none of that routine monitoring, freeing adolescents and young adults from the needle sticks and dietary calculations that define life on warfarin. For a population that includes teenagers heading to school, sports, and social lives, the convenience factor is not a luxury; it directly shapes adherence, and poor adherence to anticoagulation is one of the most dangerous failure modes in congenital heart disease care.

The study’s limitations are the familiar companions of small, single-center trials. Forty-one analyzed patients is enough to detect a large difference in satisfaction and to observe the absence of events, but not enough to rule out rare thrombotic complications that might emerge with a frequency of one or two percent. The six-month follow-up window captures the early period after valve replacement, when thrombosis risk is highest, but cannot speak to outcomes over the years and decades that these valves remain in place. The weight imbalance between groups, and the fact that the trial took place at a single tertiary referral center with experienced pediatric cardiac teams, both counsel caution before extrapolating the results universally. The authors themselves frame the findings as support for further evaluation rather than as a definitive practice-changing verdict, and that framing is scientifically appropriate.

Even so, the trial lands at a meaningful moment. Congenital heart disease survivors now outnumber congenital heart disease deaths in much of the world, and the population of adolescents and adults living with replacement pulmonary valves continues to grow. Every one of those patients faces the question of how to anticoagulate safely, and many of them are warfarin patients who endure the monitoring burden for years. Direct oral anticoagulants have already transformed stroke prevention in adult atrial fibrillation and the treatment of venous thromboembolism, but pediatric congenital heart surgery has been a more conservative frontier, partly because the evidence base in children is thin and partly because the anatomy and flow dynamics of repaired hearts differ from the conditions in which the drugs were originally validated. A randomized trial specifically in the pulmonary valve replacement population, however small, chips away at that evidence gap.

For families sitting in a pediatric cardiology clinic weighing anticoagulation options after valve replacement, the practical takeaway is one of cautious optimism rather than immediate change. The Isfahan trial suggests that rivaroxaban, dosed according to established pediatric guidelines, can protect a new pulmonary valve as effectively as warfarin over the crucial first months, with a favorable safety record and a dramatically better day-to-day experience for patients. Larger, longer, and multicenter trials will be needed before guidelines can confidently recommend the newer drug as a default, and individual factors such as valve type, heart anatomy, and bleeding risk will always shape the decision. But the direction of travel is clear: the field is moving toward anticoagulation strategies that respect both the physiology of the growing heart and the lived reality of the young person carrying it, and this study offers some of the first randomized evidence that the newer agents deserve a serious place in that conversation.

Subject of Research: Anticoagulation with rivaroxaban versus warfarin after pediatric pulmonary valve replacement

Article Title: Comparative efficacy and safety of rivaroxaban versus warfarin in patients following pulmonary valve replacement: a randomized controlled trial

Article References: Sabri, M. R., Dehghan, B., Ghasemi, M., Ahmadi, A. R., Ghaderian, M., Mahdavi, C., Nezhad, D. R., Navabfar, N., & Nourmohammadi, H. (2026). Comparative efficacy and safety of rivaroxaban versus warfarin in patients following pulmonary valve replacement: a randomized controlled trial. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07702-9

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07702-9

Keywords: rivaroxaban, warfarin, pulmonary valve replacement, pediatric cardiology, congenital heart disease, anticoagulation, thromboprophylaxis, direct oral anticoagulants, randomized controlled trial, patient satisfaction, thromboembolism, INR monitoring

The birds in the study were not killed for research. All 24 cadavers arrived opportunistically between June 2022 and November 2023, a window that coincided with regional mouse infestations. Some were donated by the university’s Veterinary Teaching Hospital after being euthanised for medical reasons, while others were roadkill collected during unrelated fieldwork. Ten raptor species and one nightjar were represented, with Eastern Barn Owls dominating the sample at ten individuals, followed by three Australian Boobook Owls. Two Wedge-tailed Eagles, two Black-shouldered Kites, a Peregrine Falcon, a Powerful Owl, a Grey Goshawk, a Brown Goshawk, a Nankeen Kestrel, a Black Kite and a Tawny Frogmouth rounded out the list. Thirteen birds were male, ten female and one of undetermined sex; fourteen were adults and ten immature.

The analytical centrepiece of the study was liquid chromatography mass spectrometry, or LC-MS, performed at the CSIRO Ecosciences Precinct in Brisbane. Because decay alters the water content of tissue, the researchers homogenised and freeze-dried liver samples before extraction, then used a multi-step process involving formic acid, cold acetonitrile and lipid-removal cartridges to isolate the rodenticide residues. The instrument, an Agilent 6546 liquid chromatography quadrupole time-of-flight mass spectrometer, ran in a data-independent mode called quadrupole-resolved all-ions analysis, screening for eight rodenticides including warfarin, brodifacoum, difethialone, flocoumafen, bromadiolone, difenacoum, coumatetralyl and pindone. Calibration curves spanning 0.01 to 1,000 parts per billion achieved correlation coefficients between 0.9683 and 0.9971, and quality-control samples spiked with known concentrations of the compounds verified the method’s accuracy across low, mid and high ranges.

The results were striking. Thirteen of the 24 birds, just over half, tested positive for rodenticides registered for use in Australia. The most frequently detected compound was warfarin, a first-generation anticoagulant, found in eleven birds. Second-generation anticoagulants, which are far more toxic and persistent, also appeared: brodifacoum in three samples, difethialone in one and flocoumafen in one. Three birds carried warfarin alongside a second-generation compound, meaning they had been exposed to multiple poisons. Perhaps most telling, only six of the thirteen rodenticide-positive birds had rodent remains in their digestive tracts at the time of death. The researchers interpret this as evidence that the poisons can bioaccumulate in liver tissue over time, lingering from past meals of poisoned prey rather than reflecting a single recent exposure.

None of the detected concentrations reached the lethal dose thresholds established for other bird species. Brodifacoum levels in the Barn Owls and a Wedge-tailed Eagle fell below the reported oral LD50 range for owls of 0.15 to 9.68 milligrams per kilogram, and the difethialone concentration in the Tawny Frogmouth, 0.1 milligrams per kilogram, sat below the LD50 values of 0.26 to 23.4 milligrams per kilogram documented for Bobwhite, Japanese Quail and Mallard. Warfarin concentrations were similarly far below the 525 to 2,150 milligrams per kilogram lethal range reported for those same test species. But sublethal does not mean harmless. Second-generation anticoagulants are highly lipid-soluble and resist metabolic breakdown, and brodifacoum has been shown to cause persistent coagulopathy in birds for up to eleven days even at doses below the lethal threshold.

The clinical consequences of such exposure can be subtle but deadly. Birds suffering sublethal anticoagulant toxicosis have been documented to show lethargy, reduced agility and wing droop, impairments that degrade hunting performance and spatial navigation. For a fast-flying owl hunting at night, a momentary lapse in coordination can be fatal in a different way: collision with a vehicle. Twelve of the fifteen birds in the study showing traumatic injuries were found on roadsides, and the authors suggest that some of these roadkill birds may have been compromised by sublethal poisoning before they ever met a car. Peak coagulopathy after a single lethal ingestion typically occurs one to four days later, and after sublethal ingestion the effects may take even longer to manifest, widening the window of vulnerability.

Disentangling poisoning from trauma is one of the study’s central methodological challenges. Internal bleeding looks much the same whether it stems from a blunt impact or a drug-induced failure of the clotting cascade, and decomposition or scavenging can destroy clots that would otherwise distinguish the two. Ten birds showed haemocoelom, a coelomic cavity filled with uncoagulated blood, and in six of those there were no grossly obvious external signs of trauma such as fractures or lacerations. Yet only four of the ten haemocoelom cases were rodenticide-positive, and the statistical association between anticoagulant presence and postmortem evidence of coagulopathy was not significant. Alternative causes of bleeding disorders complicate the picture further: three birds carried low-burden apicomplexan parasites consistent with avian malaria, two had chronic enteritis with coccidian oocysts possibly of the genus Goussia, and heavy metal toxicity and bacterial infections such as salmonellosis can produce similar pathology in wild raptors.

One statistically significant pattern did emerge, and it concerned age. Immature birds were significantly more likely to carry higher brodifacoum concentrations than adults, a correlation with an f-value of 5.15 and a p-value of 0.03. The authors offer several non-exclusive explanations: inexperienced young hunters may target weakened, poisoned prey more readily; older birds may metabolise or eliminate the compound more efficiently or simply have longer intervals between exposures; or heavily affected juveniles may never survive to adulthood at all. The researchers caution, however, that the small sample size and a confidence interval hovering near zero mean the finding should be treated as a hypothesis generator rather than a settled conclusion. Species-level dietary differences add another layer of complexity, since rodent specialists such as Barn Owls and Black-shouldered Kites face theoretically higher exposure risk than bird-eating specialists like goshawks.

The conservation stakes extend beyond the species examined, all of which are currently listed as Least Concern by the International Union for Conservation of Nature. The Powerful Owl, despite its global status, numbers only an estimated 2,200 to 2,800 mature individuals, and the Grey Goshawk is estimated at fewer than 10,000 birds with a declining trend and Endangered classification in several Australian states. Sublethal poisoning that reduces foraging success, body condition and reproductive output, effects documented in vulture studies in the Pacific Northwest, could push such populations toward localised declines long before outright poisoning deaths register. Australian raptor populations remain poorly studied overall, making it difficult to assess how much hidden damage rodenticides are doing.

The study’s most policy-relevant finding may be its challenge to current Australian guidelines, which favour first-generation rodenticides such as warfarin over second-generation products on the assumption that they break down faster in rodents and pose less secondary risk. Warfarin was, after all, the most common residue in these Queensland birds. The authors point instead to coumatetralyl, another first-generation anticoagulant regarded as safer for predatory birds: mammals are generally more sensitive to it than birds, allowing lower effective doses, and while warfarin resistance has been documented in Australian rodents, no coumatetralyl resistance has yet been recorded there. The team calls for physiological studies of exposed raptors, rodent toxicity testing to track resistance, and surveys of rodenticide users to map what, how much and how often is being deployed. Until then, the poisons meant for mice appear to be quietly accumulating in the livers of the owls, eagles and falcons that share those fields, a debt the ecosystem may only now be beginning to itemise.

Subject of Research: Sublethal anticoagulant rodenticide exposure in deceased predatory birds in south-east Queensland, Australia

Article Title: Evaluating sublethal anticoagulant rodenticide exposure in deceased predatory birds of South-East Queensland, Australia

Article References: Low, Z., Murray, P. J., Naseem, N., McGilp, D., Doneley, B., Beale, D. J., Biggs, L., & Gonzalez-Astudillo, V. (2024). Evaluating sublethal anticoagulant rodenticide exposure in deceased predatory birds of South-East Queensland, Australia. Discover Toxicology, 1(1), Article 13. https://doi.org/10.1007/s44339-024-00016-4

Image Credits: AI Generated

DOI: 10.1007/s44339-024-00016-4

Keywords: anticoagulant rodenticides, raptors, owls, warfarin, brodifacoum, secondary poisoning, wildlife toxicology, LC-MS, Australia, Queensland, coagulopathy, conservation

The research, published in eClinicalMedicine, drew on the Clinical Practice Research Datalink Aurum database, an anonymized repository of medical records covering more than 50 million patients registered with over 1800 general practices across England. The investigators linked these primary care records to Hospital Episode Statistics, which capture every admission to publicly funded hospitals in the country, allowing them to track both routine diagnoses and serious exacerbations of lung disease. From this vast data resource, they assembled a cohort of 444,668 adults aged 50 and over with a physician diagnosis of COPD, who together contributed nearly 2.3 million person-years of follow-up. Within this group, 37,645 people, or 8.5 percent, were newly diagnosed with atrial fibrillation during the study window.

The scale of the comorbidity problem is difficult to overstate. COPD affects more than 390 million people worldwide and is the third leading cause of death globally, while atrial fibrillation touches over 52 million lives. Previous meta-analyses have estimated that patients with COPD face roughly twice the risk of developing atrial fibrillation compared with those without the lung disease, and that risk climbs as lung function deteriorates. The new study reinforces this dose-response relationship with unusual granularity. Incidence rates rose consistently with age, were higher in men than women across every age band, and were markedly elevated among patients with more severe COPD, whether severity was measured by forced expiratory volume in one second, breathlessness scores, or recent exacerbations requiring hospitalization. Patients hospitalized for a severe COPD flare in the previous year showed incidence rates above 55 per 1000 person-years by 2022, several times higher than those with well-preserved lung function.

The temporal pattern also tells a story about modern healthcare. After a gradual year-on-year climb, incidence plateaued between 2016 and 2019, then dropped 22 percent in 2020 compared with 2019, a dip the authors attribute to reduced access to primary care during the COVID-19 pandemic. The rebound afterward suggests the underlying trend was never interrupted, merely masked. The researchers note that the rising trajectory mirrors patterns seen in the general UK population, implying that improved detection and better survival among people with atrial fibrillation risk factors, rather than something unique to COPD, may be driving much of the increase. Still, the consistency of the elevation across every marker of COPD severity points to a genuine biological contribution, likely involving chronic inflammation, hypoxia, and the structural cardiac changes that accompany long-standing lung disease.

Why does this matter so much? Because atrial fibrillation in a COPD patient is more dangerous than atrial fibrillation alone. Recent cohort evidence indicates that people with both conditions face approximately 1.6 times the risk of ischemic stroke compared with those who have atrial fibrillation without COPD. Oral anticoagulants are the cornerstone of stroke prevention in atrial fibrillation, and current guidelines recommend that treatment decisions be made independently of COPD status. Yet the real-world evidence on whether this actually happens has been sparse and contradictory, with some studies suggesting higher anticoagulation rates in COPD patients and others suggesting lower or equivalent rates.

The new findings go further than any previous work by tracking prescribing trends over thirteen years. Among the 34,851 patients newly diagnosed with atrial fibrillation during follow-up, 66.3 percent received an oral anticoagulant within a year of diagnosis. The rate of initiation nearly tripled over the study period, from 10.3 prescriptions per 100 person-months in 2010 to 30.1 per 100 person-months in 2022, a 2.9-fold increase. The most dramatic rise occurred among patients aged 90 and older, whose initiation rate was more than nine times higher in 2022 than in 2010, albeit from a very low baseline. This transformation was driven almost entirely by the direct oral anticoagulants, or DOACs, which received European approval for stroke prevention in 2011. Warfarin and other vitamin K antagonists, once the only option, collapsed to a 96 percent lower initiation rate by 2022, while DOAC use surged 64-fold between 2012 and 2022.

The fine-grained prescribing data reveal how completely the therapeutic landscape has changed. Apixaban emerged as the dominant agent, peaking at 208.1 prescriptions per 1000 person-months in 2021 and accounting for 61.6 percent of all oral anticoagulants started between 2020 and 2022. Edoxaban, introduced in 2016, overtook rivaroxaban by 2020 and then jumped from 49.4 to 95.4 prescriptions per 1000 person-months between 2021 and 2022. Rivaroxaban, an early favorite, peaked in 2016 and declined steadily thereafter. Dabigatran, the first DOAC approved, never gained significant traction. Notably, these patterns closely match prescribing trends reported in atrial fibrillation patients generally, suggesting that the presence of COPD did not materially alter which drug clinicians chose, only, in some cases, whether they prescribed one at all.

And that is where the treatment gap emerges. Despite the overall tripling of anticoagulation, several high-risk groups were persistently less likely to receive treatment. Patients aged 90 and older had the lowest initiation rates of any age group throughout the study, even though stroke risk climbs steeply with age and guidelines recommend anticoagulation for most patients with atrial fibrillation over 75. Non-White patients were prescribed anticoagulants less often than White patients, echoing documented disparities in atrial fibrillation care more broadly. Most strikingly, people with the most severe COPD, identified by low percent-predicted lung function, severe breathlessness, or recent hospitalization for an exacerbation, consistently received fewer prescriptions than those with milder disease, a pattern that held across all years, ages, and sexes. Patients with chronic kidney disease, liver disease, a history of bleeding, cancer, or dementia were also less likely to be treated.

The authors caution that these patterns may not reflect inappropriate care alone. Contraindications, frailty, polypharmacy, and patient preferences all legitimately shape prescribing decisions, and clinicians may reasonably hesitate before adding a blood thinner to a regimen already burdened by multiple respiratory medications. Yet the concern about physician hesitancy is hard to dismiss, because evidence on the safety and efficacy of anticoagulants specifically in patients with coexisting COPD and atrial fibrillation remains thin. Without dedicated trials or robust observational outcome data in this population, uncertainty itself becomes a barrier to treatment, and the patients facing the highest thromboembolic risk are left in a zone of clinical ambiguity.

The study has limitations worth noting. The database does not capture prescriptions issued by specialists or during hospitalizations, which may lead to modest underestimation of prescribing rates, though the central role of general practitioners in the UK system likely mitigates this. Restricting the cohort to adults over 50 reduced but did not eliminate the possibility of misclassifying some asthma patients as having COPD. The ethnicity-stratified analyses aggregated small numbers of non-White patients into a single category, limiting insight into specific minority subgroups, and the cohort included only individuals with COPD, so comparisons with the general population are indirect. Even so, the sheer size of the cohort, the representativeness of the data, and the consistency of results across sensitivity analyses using multiple imputation lend considerable weight to the conclusions. The message for clinicians and health systems is clear: as atrial fibrillation becomes increasingly common among people with COPD, stroke prevention must keep pace, and the oldest, sickest, and most ethnically marginalized patients, precisely those at greatest risk, should not be left behind. Integrated care pathways and routine bidirectional screening for both conditions, identified as research priorities by the American Thoracic Society, may offer a route forward, but the first step is recognizing that a growing treatment gap exists at all.

Subject of Research: Temporal trends in atrial fibrillation incidence and oral anticoagulant prescribing among adults with COPD in UK primary care

Article Title: Trends in the incidence of atrial fibrillation and the prescription of oral anticoagulants in adults with chronic obstructive pulmonary disease in UK primary care (2010–2022): a cohort study

Article References: Murray, B., Beradid, S., Ernst, P., Suissa, S., & Renoux, C. (2026). Trends in the incidence of atrial fibrillation and the prescription of oral anticoagulants in adults with chronic obstructive pulmonary disease in UK primary care (2010–2022): a cohort study. eClinicalMedicine, 100, Article 104245. https://doi.org/10.1016/j.eclinm.2026.104245

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104245

Keywords: atrial fibrillation, COPD, oral anticoagulants, DOACs, stroke prevention, UK primary care, CPRD, cohort study, health disparities, warfarin, apixaban, epidemiology

The adrenal glands are small but vital endocrine organs that produce cortisol, aldosterone, and other hormones essential for blood pressure regulation, salt and water balance, and the body’s response to stress. Because of their exceptionally rich blood supply and their unusual venous drainage into a single central vein, the adrenal glands are surprisingly vulnerable to a rare but well-described catastrophe: thrombosis of the adrenal vein, which cuts off the outflow of blood, causes hemorrhagic infarction, and leads to bleeding into the gland itself. In other words, the hemorrhage that appears on a CT scan is not a simple bleed but the end result of a clot that choked off the gland’s circulation. This mechanism explains why adrenal hemorrhage is a recognized, if uncommon, complication of antiphospholipid syndrome, an autoimmune condition in which the immune system mistakenly produces antibodies against phospholipid-binding proteins in the blood.

What makes the Palestinian patient’s case so unusual is that the hemorrhage affected only one adrenal gland. Adrenal insufficiency, the clinical state that arises when the glands fail to produce enough cortisol, is far more commonly associated with bilateral adrenal involvement, because the remaining healthy gland can usually compensate when only one side is damaged. In this patient, however, a large right adrenal hematoma was accompanied by severe biochemical derangement, including a profoundly low serum sodium concentration and a morning serum cortisol level of just 2.8 micrograms per deciliter, a value far below the threshold expected in a critically ill patient. These findings raised immediate concern that the single damaged gland had left him functionally unable to mount a cortisol response, a condition that can rapidly become life-threatening if untreated.

The diagnostic journey began with computed tomography, which revealed the large right adrenal hematoma and effectively excluded other causes of the patient’s abdominal pain. But the laboratory workup added the crucial pieces of the puzzle. His platelet count was low, a finding known as thrombocytopenia that is common in antiphospholipid syndrome. More tellingly, his activated partial thromboplastin time, or aPTT, a standard measure of blood clotting, was markedly prolonged. In most clinical contexts, a prolonged aPTT suggests a bleeding tendency, and one might expect such a patient to hemorrhage more easily. Yet in antiphospholipid syndrome, the prolongation is a laboratory artifact caused by antibodies that interfere with the phospholipid reagents used in the test, even as the patient’s actual physiology is prothrombotic. This is the famous lupus anticoagulant paradox: a test that suggests poor clotting in a patient whose disease is defined by clotting.

To distinguish between a clotting factor deficiency and an inhibitor, the team performed a mixing study, in which the patient’s plasma is combined with normal pooled plasma. If the prolonged clotting time corrects with the addition of normal plasma, the problem is a missing factor; if it fails to correct, an inhibitor is present. In this patient, the mixing study failed to correct the aPTT, pointing squarely toward an inhibitor. Follow-up testing confirmed a positive lupus anticoagulant, and subsequent assays revealed high-titer anticardiolipin antibodies and high-titer anti-beta2-glycoprotein I antibodies. Together with the lupus anticoagulant, these three positive tests constitute the triple-positive antiphospholipid antibody profile, the highest-risk serological pattern in the syndrome, associated with the greatest likelihood of thrombotic events. The combination of adrenal hemorrhage, thrombocytopenia, and the characteristic coagulation abnormalities established the diagnosis of antiphospholipid syndrome presenting for the first time through its adrenal complication.

Once hematology specialists reviewed the case, they favored APS-associated thrombotic adrenal injury as the underlying mechanism, and treatment was initiated accordingly. The patient received therapeutic anticoagulation, first with enoxaparin, a low-molecular-weight heparin delivered by injection, and later transitioned to warfarin, an oral vitamin K antagonist that remains the mainstay of long-term anticoagulation in antiphospholipid syndrome. At the same time, the adrenal insufficiency was treated with hydrocortisone, a replacement glucocorticoid that restores the missing cortisol, and fludrocortisone, a mineralocorticoid that helps the body retain sodium and maintain blood pressure. This dual approach addressed both faces of the disease simultaneously: preventing further clots with anticoagulation while replacing the hormones the damaged gland could no longer produce.

The clinical course was encouraging. During follow-up, the patient showed progressive improvement in his symptoms, his laboratory values normalized, including his kidney function and electrolytes, and repeat imaging demonstrated a marked reduction in the size of the adrenal hematoma. The recovery underscores an important point about adrenal hemorrhage in the context of antiphospholipid syndrome: with prompt anticoagulation and appropriate hormone replacement, even a dramatic presentation can resolve substantially, and patients can return to good health. It also highlights the value of multidisciplinary care, since the case required coordinated input from internal medicine, endocrinology, hematology, and radiology to arrive at the correct diagnosis and treatment plan.

For the wider medical community, the authors argue that this case carries a clear message. When clinicians encounter a patient with unexplained adrenal hemorrhage, particularly when it is accompanied by thrombocytopenia, evidence of adrenal dysfunction, and a markedly prolonged aPTT, antiphospholipid antibody testing should be high on the differential. The alternative is a dangerous diagnostic delay, in which the hemorrhage is attributed to trauma or other causes and the underlying prothrombotic disorder goes untreated, leaving the patient exposed to further clots in the adrenal glands, the brain, the lungs, or the deep veins of the legs. Equally important is the early recognition of adrenal insufficiency itself, because untreated cortisol deficiency in a stressed, febrile patient can precipitate an adrenal crisis, a medical emergency characterized by hypotension, shock, and death if glucocorticoid replacement is not given immediately.

The case also illustrates the subtlety of the antiphospholipid syndrome’s laboratory signature. Lupus anticoagulant antibodies earned their name because they were first identified in patients with lupus and because they prolong clotting tests in a test tube, yet they are among the strongest laboratory predictors of thrombosis in the body. This inversion of expectations, in which a bleeding test predicts clotting, is one of the most counterintuitive phenomena in clinical medicine, and cases like this one, where the paradox plays out in a single organ, provide vivid teaching material for physicians in training. The triple-positive profile identified in this patient, with all three major antiphospholipid antibody tests positive at high titer, marks him as requiring careful, long-term anticoagulation management and monitoring for future thrombotic risk.

Published as an open-access report with the patient’s written informed consent, the study adds to the limited literature on unilateral adrenal hemorrhage as the initial manifestation of antiphospholipid syndrome. It demonstrates that clinically significant adrenal insufficiency can develop even when only one gland is visibly affected, that the hemorrhagic appearance of adrenal injury should not obscure its thrombotic origin, and that a simple mixing study followed by targeted antibody testing can unravel a diagnosis that might otherwise remain hidden. For a young man whose vague symptoms of fever, pain, and fatigue masked a rare autoimmune catastrophe, the systematic application of basic clinical reasoning, from CT imaging to coagulation studies to antibody panels, made the difference between a mysterious illness and a treatable disease with a clear path to recovery.

Subject of Research: Adrenal hemorrhage and adrenal insufficiency as the initial presentation of triple-positive antiphospholipid syndrome

Article Title: Unilateral adrenal hemorrhage and adrenal insufficiency as the initial presentation of triple-positive antiphospholipid syndrome: a case report

Article References: Alshamisti, M. I., Deeb, N., Almasalmah, A., Amayre, S., Kurdi, L., Atawnah, S. I., & Ibriwesh, M. (2026). Unilateral adrenal hemorrhage and adrenal insufficiency as the initial presentation of triple-positive antiphospholipid syndrome: a case report. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02609-z

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02609-z

Keywords: adrenal hemorrhage, adrenal insufficiency, antiphospholipid syndrome, triple-positive antiphospholipid antibodies, lupus anticoagulant, thrombocytopenia, cortisol, anticoagulation, case report, endocrine disorders, hydrocortisone, warfarin