The patient arrived at the emergency department with three days of high-grade fever, reaching 103 degrees Fahrenheit, accompanied by the classic hallmarks of dengue: headache, retro-orbital pain behind the eyes, and generalized body aches. He had no vomiting, diarrhea, cough, or any bleeding manifestations, and no chronic medical conditions, prior surgeries, or relevant family history. He did not smoke, drink alcohol, or use recreational drugs. On examination he appeared ill and febrile, with a pulse of 110 beats per minute and a blood pressure of 115/80 mmHg, but his heart, lungs, abdomen, and neurological status were otherwise unremarkable. In short, he presented as a textbook case of uncomplicated dengue.

Laboratory testing confirmed the diagnosis. The dengue NS1 antigen came back positive, malaria parasites were absent, and ELISA-based serology ruled out other viral infections. His hemoglobin stood at 13 g/dL and his platelet count at 192,000 per microliter, well within the normal range, which would later prove to be one of the most instructive features of the case. His leukocyte count was initially elevated at 12,000 per microliter before settling to 4,600. More ominous was the coagulation picture: while his standard coagulation profile was normal, his D-dimer, a breakdown product of cross-linked fibrin that serves as a molecular flag for active clot formation and dissolution, was dramatically elevated at 9,968 ng/mL, later declining to 4,068 ng/mL. Inflammatory markers told a similar story of a body under siege, with C-reactive protein at 142 mg/L against a normal threshold of 10, procalcitonin at 0.57 ng/mL, and an erythrocyte sedimentation rate of 54 mm/h.

The turning point came on the sixth day of hospitalization, roughly the ninth day of illness, when the patient developed sudden painful swelling of the right lower limb extending from calf to thigh, together with progressive shortness of breath on exertion. The limb was visibly swollen up to the groin, red, warm, and tender, with increased calf and thigh circumference, though peripheral pulses remained intact. He remained hemodynamically stable apart from mild tachycardia, with a blood pressure of 105/70 mmHg and an oxygen saturation of 93 percent on room air. Doppler ultrasonography confirmed deep vein thrombosis, and because his dyspnea worsened, the team proceeded to CT pulmonary angiography. The scan revealed bilateral pulmonary emboli and dilatation of the right cardiac chambers, a sign that the clots lodging in the pulmonary arteries were forcing the right side of the heart to pump against dangerous resistance.

Imaging then uncovered a further puzzle. A chest radiograph showed a cavitary lesion in the right lung with mild cardiomegaly, and high-resolution computed tomography revealed that cavity surrounded by pneumonic consolidation, minimal bilateral pleural effusions, and basal atelectatic changes. Cavitary lung lesions typically raise the specter of tuberculosis, lung abscess, fungal infection, or malignancy, each of which could independently predispose a patient to clotting. The team therefore cast a wide diagnostic net: sputum examination, acid-fast bacilli smears, and GeneXpert testing were negative for Mycobacterium tuberculosis, blood cultures grew no bacterial or fungal pathogens, and bronchoscopy with bronchoalveolar lavage found only mucopurulent secretions with no organisms on Gram stain, no growth on culture, and no malignant cells on cytology. Transthoracic echocardiography showed preserved left ventricular function with an ejection fraction of 64 percent, no intracardiac vegetations, and a positive McConnell sign, a regional pattern of right ventricular dysfunction considered suggestive of acute pulmonary embolism.

The authors argue that the most likely explanation for the cavity is pulmonary infarction, tissue death downstream of the embolic obstruction, which can occasionally cavitate when vascular blockage is severe. The temporal relationship between the dengue infection and the thrombotic event, combined with a negative thrombophilia workup and the patient’s young age, pointed toward a transient, infection-associated prothrombotic state rather than an inherited clotting disorder or occult cancer. The differential diagnosis nonetheless included septic pulmonary emboli, secondary bacterial pneumonia, and malignancy, and the authors note that unexplained or recurrent venous thromboembolism should always prompt consideration of hidden malignancy, citing a prior report in which deep vein thrombosis was the presenting feature of uterine leiomyosarcoma.

The mechanistic picture emerging from the dengue literature is one of coordinated disruption of hemostasis. The authors outline several converging pathways: molecular mimicry between viral antigens and coagulation factors generating cross-reactive autoantibodies; direct endothelial dysfunction driven in part by the dengue NS1 protein; infection-induced upregulation of tissue factor in monocytes and endothelial cells; and a cytokine storm that amplifies both inflammation and coagulation activation. Critically, this case demonstrates that clinically significant thrombosis can occur even when platelet counts remain normal. Previous analyses have documented venous thrombosis in dengue patients with median platelet counts as low as 52,000 per cubic millimeter, but this patient never developed thrombocytopenia during hospitalization, underscoring that the absence of low platelets offers no reassurance against the thrombotic complication.

The timing also fits an emerging pattern. In an analysis of 19 previously reported cases of spontaneous venous thrombosis in dengue cited by the authors, the median onset of thrombosis was six days after fever began, with serious thrombotic events generally clustering between days 5 and 10 of illness, the transition from the acute phase to recovery. Lower limb deep vein thrombosis was the dominant manifestation, accounting for 68 percent of cases, most often involving the right side and the external iliac, common femoral, and popliteal veins. This patient’s right lower limb clot extending from calf to thigh, with bilateral pulmonary embolism on top, represents an unusually severe expression of that same tendency. His markedly elevated C-reactive protein also aligned with evidence that more intense inflammatory responses accompany severe dengue, where mean CRP levels of roughly 50 mg/L have been recorded against about 22 mg/L in non-severe disease.

Treatment required navigating a genuine therapeutic dilemma: anticoagulating a dengue patient in whom bleeding is the classically feared complication. The team initiated weight-based therapeutic enoxaparin at 60 mg subcutaneously twice daily for the approximately 60-kg patient, alongside intravenous paracetamol, fluids, broad-spectrum antimicrobials with meropenem and linezolid given concern for secondary bacterial infection, and nebulized bronchodilators and corticosteroids for respiratory symptoms. In the published series, 57.8 percent of patients received low-molecular-weight heparin, anticoagulation was tolerated even amid thrombocytopenia, and all patients recovered without incident. Yet the literature still lacks formal guidelines for managing dengue-associated pulmonary embolism, and the authors emphasize that the decision to anticoagulate remains difficult in the face of bleeding risk. This patient improved steadily, was discharged on day thirteen with apixaban 10 mg twice daily tapering to 5 mg twice daily for a total of six months of anticoagulation, and at four-week follow-up his dyspnea and leg swelling had resolved, repeat Doppler ultrasound showed interval improvement, and chest CT showed partial resolution of the cavitary lesion.

The case carries two forward-looking warnings. First, because the patient demonstrated right ventricular dysfunction from bilateral pulmonary emboli, he faces a risk of chronic thromboembolic pulmonary hypertension, a disabling late complication that demands extended monitoring. Second, and more broadly, the authors urge clinicians caring for dengue patients to stay alert for thrombotic symptoms during the recovery phase, when vague complaints such as unilateral limb swelling or exertional breathlessness may be the only clues to a clot that imaging will confirm. Early recognition, timely diagnosis with tools such as D-dimer measurement, Doppler ultrasound, and CT angiography, and prompt anticoagulation can prevent life-threatening outcomes in a complication that remains poorly recognized but is, as this case shows, very much preventable.

Subject of Research: Venous thromboembolism as a complication of dengue fever

Article Title: Post‐Dengue Deep Vein Thrombosis Complicated by Pulmonary Embolism: A Case Report

Article References: Nisar, S., Mushtaq, H., Khan, M. H., Sajjad, F., Afridi, A., Fatima, N. E., & Kamil, K. A. (2026). Post‐Dengue Deep Vein Thrombosis Complicated by Pulmonary Embolism: A Case Report. Clinical Case Reports, 14(10), Article e73642. https://doi.org/10.1002/ccr3.73642

Image Credits: AI Generated

DOI: 10.1002/ccr3.73642

Keywords: dengue, deep vein thrombosis, pulmonary embolism, venous thromboembolism, hypercoagulability, D-dimer, anticoagulation, enoxaparin, apixaban, NS1 antigen, pulmonary infarction, case report

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: 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. (n.d.). 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 study, published in BMC Geriatrics by a team of hospital pharmacists and pharmacoepidemiologists affiliated with Assistance Publique–Hôpitaux de Paris and Paris-Saclay University, set out to measure how often DOAC prescriptions in hospitalized older adults deviated from European Society of Cardiology (ESC) guidelines, and whether the situation had improved since a comparable assessment in 2018. The answer, in short, is that it had not.

Between November 2022 and May 2023, the researchers consecutively enrolled older adults who were already taking a DOAC before admission and who stayed in one of three French university hospitals for more than 24 hours. The participating departments spanned cardiology, internal medicine, post-emergency care, and acute geriatrics, giving a broad picture of real-world prescribing across the acute care pathway. In total, 536 patients were eligible, with a mean age of 84.1 years and a slight majority of women; 421 patients formed the primary analysis cohort.

The pharmacological profile of the cohort reflected current practice. Apixaban dominated, accounting for 70.1 percent of prescriptions, and atrial fibrillation was the indication in 83.6 percent of cases. This matters because apixaban, like all DOACs, has a narrow therapeutic window whose appropriateness hinges on patient-specific factors: renal function, age, body weight, and the indication being treated. Unlike warfarin, which is monitored with routine blood tests, DOAC dosing is fixed at prescription time, so an error at the moment of prescribing persists silently until harm occurs.

Using ESC guidelines as the benchmark, the team classified prescriptions as appropriate or inappropriate at two critical moments: hospital admission and hospital discharge. On admission, 32.0 percent of prescriptions were judged inappropriate. By discharge, the figure had fallen to 24.9 percent, a statistically significant improvement (p = 0.004), suggesting that the hospital stay does correct some errors, but leaves a substantial fraction of patients heading home with potentially unsafe anticoagulation.

The consequences of such errors are not abstract. An excessive dose in a frail 85-year-old with declining kidney function increases the risk of major bleeding, including intracranial hemorrhage. An insufficient dose, conversely, can mean therapeutic failure, allowing a stroke or systemic embolism to occur despite the patient dutifully taking their medication. In older patients with polypharmacy, where DOACs interact with other drugs and renal clearance is often reduced, the margin for error shrinks further, which is why inappropriate prescribing is considered a major patient safety concern in geriatric care.

To understand who was most at risk, the researchers used logistic regression to identify predictive factors for inappropriate prescribing. Two variables stood out at admission: age over 80 years nearly doubled the odds of an inappropriate prescription (odds ratio 1.80, 95 percent confidence interval 1.20–2.72), and elevated serum creatinine above 133 µmol/L, a marker of impaired kidney function, similarly raised the odds (OR 1.84, 95 percent CI 1.13–2.98). At discharge, age over 80 remained a strong risk factor (OR 2.71, 95 percent CI 1.63–4.61), while a body weight below 60 kilograms was unexpectedly protective (OR 0.42, 95 percent CI 0.25–0.69), possibly because clinicians scrutinize low-weight patients more carefully when selecting doses.

The renal connection deserves particular emphasis. DOACs are cleared substantially by the kidneys, and estimates of glomerular filtration rate in older adults vary depending on the formula used, whether Cockcroft–Gault, MDRD, or CKD-EPI. The study’s authors assessed prescriptions against the Summary of Product Characteristics for each molecule, which specify dose reductions based on renal function, age, and weight. When kidney function is overestimated, or when a hospitalization changes a patient’s renal status without the prescription being adjusted, the fixed daily dose can quickly become dangerous. Advanced age and impaired renal function, the two risk factors identified here, are precisely the conditions that make this pharmacokinetic tightrope hardest to walk.

Perhaps the most sobering finding is the comparison with 2018. Using chi-squared tests, the team compared their results with data collected five years earlier and found no significant changes. Despite growing awareness of DOAC dosing pitfalls, updated guidelines, and the expansion of clinical pharmacy services in French hospitals, the rate of inappropriate prescribing in this vulnerable population has remained essentially flat. The authors conclude that further efforts to optimize DOAC prescribing are warranted, and they point toward concrete interventions: pharmacist-led medication reviews at admission and discharge, and integrated prescribing tools embedded in electronic medical records that would automatically flag doses inconsistent with renal function, age, and weight.

The study has the strengths and limits of its design. As a prospective observational study, it captures real prescribing behavior rather than idealized trial conditions, and its multicenter scope across four department types strengthens generalizability within the French hospital system. But it also reflects a single country’s practice in a single year, and appropriateness was defined by ESC guidelines rather than patient-specific outcomes, so the findings measure guideline concordance rather than directly measured harm. Even so, the message is clear and actionable: the transition points of hospital care, admission and discharge, remain moments where older patients on DOACs are at elevated risk of a prescribing error, and after years of stagnation, systematic medication reconciliation and decision support may be the tools that finally bend the curve.

Subject of Research: Appropriateness of direct oral anticoagulant prescribing in hospitalized older adults

Article Title: Appropriateness prescriptions of direct oral anticoagulants in hospital in 2023 in the older population: a prospective observational multicenter study

Article References: Rodier, T., Gibert, A., Lepors, A., Fernandez, C., Hindlet, P., Savoldelli, V., & Schwab, C. (2026). Appropriateness prescriptions of direct oral anticoagulants in hospital in 2023 in the older population: a prospective observational multicenter study. BMC Geriatrics. https://doi.org/10.1186/s12877-026-08330-9

Image Credits: AI Generated

DOI: 10.1186/s12877-026-08330-9

Keywords: DOACs, anticoagulants, older adults, prescribing appropriateness, medication safety, atrial fibrillation, apixaban, renal function, polypharmacy, hospital discharge, pharmacist-led medication review, geriatrics