Thromboelastography to monitor anticoagulation in ICU patients receiving a continuous infusion of unfractionated heparin.

Therapeutic intensity unfractionated heparin (UFH) infusions require titration to target a therapeutic activated partial thromboplastin time (aPTT) or UFH anti-Xa. At The Johns Hopkins Hospital (JHH) and Johns Hopkins Bayview Medical Center (JHBMC), a computerized nurse-managed UFH calculator was built into the electronic health record (EHR) to improve adherence to institutional nomograms. This study evaluated the impact of implementation of an EHR-embedded UFH calculator on nurse-managed UFH nomogram adherence. A retrospective, observational cohort study was conducted at 2 institutions within one health system. Patients admitted to adult services who received nurse-managed UFH for at least 4 consecutive hours were included. Patients admitted between March 2019 and March 2021 constituted the pre-implementation cohort and patients admitted August 2021 through August 2023 were included in the post-implementation cohort. The primary outcomes were nurse-managed UFH nomogram adherence, management of critical aPTT results, and therapeutic aPTT achievement. A total of 2128 patients were included in the pre-implementation cohort and 2517 in the post-implementation cohort. The mean age was 61 for both the pre- and post-implementation cohorts. The post-implementation cohort experienced an increase in adherence to initial bolus dose recommendations when compared with the pre-implementation cohort (85.9% vs 92%, P < 0.001) as well as increased adherence to correct initial infusion doses (80.8% vs 95.9%, P < 0.001). Infusion dose adjustment error rates were reduced in the post-implementation cohort (4.9% vs 1.5%, P < 0.001). Fewer patients experienced nomogram nonadherence errors in the post-implementation cohort (20.2% vs 5.3%, P < 0.001). Critical aPTT nomogram adherence improved after calculator implementation for resumption at the recommended dose (72.4% vs 94.0%, P < 0.001). However, the time to therapeutic aPTT achievement was similar between pre-implementation and post-implementation cohorts. A stewardship initiative to implement an EHR-embedded nurse-managed UFH calculator significantly increased adherence to nomogram-recommended initial doses and dose adjustments.

Heparin-incorporated whey protein isolate-derived hydrogels with an intended dual function as snakebite wound dressings and drug delivery systems inhibit spitting cobra venom-induced cytotoxicity.

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with severe cardiac or respiratory failure, but it is associated with a high risk of thrombotic and bleeding complications. Unfractionated heparin (UFH) remains the most frequently used anticoagulant, largely due to historical practice and longstanding clinical familiarity, despite the absence of robust evidence from randomized controlled trials. Alternative strategies-including direct thrombin inhibitors (DTIs), low-molecular-weight heparins (LMWHs), nafamostat mesylate (NM), and no anticoagulation-are increasingly being explored. However, a comprehensive and contemporary comparison of these approaches has been lacking. We conducted a comprehensive search of PubMed/MEDLINE, EMBASE, and CENTRAL through March 2025, supplemented by manual searches of reference lists. We included randomized controlled trials and observational studies including patients 16 years or older receiving ECMO for ≥ 24 h that compared any anticoagulation strategy with another or with no anticoagulation. The primary outcome was thromboembolic events; secondary outcomes included bleeding and mortality. Risk of bias was assessed using validated tools. Meta-analyses were performed using a multivariable random-effects model, with prespecified subgroup analyses by ECMO modality (venoarterial [VA], venovenous [VV], or mixed) and subsequent sensitivity analyses. Twenty-one observational studies involving 2 775 adult ECMO patients were included, with UFH serving as the comparator in all studies. DTIs showed reduced thromboembolism (OR 0.73; 95% CI: 0.53-0.99) and were associated with significantly lower bleeding (OR 0.51; 95% CI: 0.39-0.67) and mortality (OR 0.70; 95% CI: 0.52-0.94), confirmed in a sensitivity analysis. LMWH was associated with significantly reduced odds of thromboembolic events (OR 0.26; 95% CI: 0.13-0.55), as well as showing a favorable bleeding profile (OR 0.46; 95% CI: 0.25-0.87), yet no significant difference in mortality (OR0.80; 95% CI: 0.30-2.14). While no anticoagulation reduced the odds for bleeding (OR 0.17; 95% CI: 0.07-0.38) and NM showed no significant differences, both had wide confidence intervals, limiting interpretation. Heterogeneity for LMWH was low for efficacy and bleeding, yet substantial for mortality; for DTI, low to moderate; for no anticoagulation, low; and for NM, substantial to high on all comparisons. In this systematic review and meta-analysis, DTIs and LMWH appear to be effective and safe alternatives to UFH in adult ECMO, with consistent reductions in thromboembolic and bleeding events and a survival benefit observed for DTIs. These findings support reconsideration of UFH as the default anticoagulant and favor a more prominent role for alternative strategies in clinical practice. PROSPERO CRD42022363588.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment-elevation myocardial infarction (STEMI). We investigated the benefits and safety of pretreatment with unfractionated heparin (UFH) in patients with STEMI referred to primary PCI. In HEPARIN-STEMI (Pretreatment With Unfractionated Heparin for ST Elevation Myocardial Infarction)-a single-center, open-label, randomized controlled trial-patients with STEMI with ≤6 hours symptom duration were assigned to receive either a 70- to 100-IE/kg bolus of UFH at first prehospital medical contact plus a supplemental dose before PCI, adjusted to activated clothing time ≥250 seconds, or to a control group receiving standard UFH at the time of PCI. The primary efficacy end point was TIMI (Thrombolysis in Myocardial Infarction) flow grade 2-3 in the infarct-related artery at initial coronary angiography. The primary safety end point was BARC (Bleeding Academic Research Consortium) type 3-5 bleeding during the index hospital stay. From March 2022 to February 2025, 298 patients were randomized to UFH pretreatment and 295 to the control group. The groups were comparable in age, sex, risk factors, previous cardiovascular events, and median delay from symptoms to coronary angiography (145 versus 150 minutes; P=0.814). The median time from UFH pretreatment to coronary angiography was 60 minutes (25th-75th interquartile range, 47-55 minutes). TIMI flow grade 2-3 in the infarct-related artery was documented in 43% of patients with UFH pretreatment and 27% of patients in the control group (relative risk, 1.59 [95% CI, 1.27-1.98]; P<0.001), with no significant difference in BARC type 3-5 bleeding (2.4% versus 2.0%; relative risk, 1.16 [95% CI, 0.39-3.45]; P=0.789). In patients with STEMI undergoing primary PCI, in a mature STEMI network, pretreatment with UFH at first prehospital medical contact was associated with an absolute 16% increase in infarct-related artery patency without an increased risk of bleeding. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05247424.

Hand, foot, and mouth disease (HFMD) is a common childhood infection caused by enteroviruses, which exhibit distinct regional and seasonal epidemiological patterns. Wastewater-based epidemiology is a crucial tool for monitoring population infection dynamics and viral subtype distribution. However, the lack of effective on-site viral detection methods limits timely early warning and effective surveillance of infectious disease outbreaks. This study developed a one-pot RT-RPA/CRISPR-Cas12a assay-based, string-powered flywheel microfluidic chip for the multiplex detection of HFMD viruses in wastewater. First, by leveraging the regulatory effect of heparin sodium on CRISPR/Cas12a activity, a one-pot RT-RPA/CRISPR-Cas12a system was constructed to detect four major subtypes of HFMD virus (EV-A71, CV-A16, CV-A6, and CV-A10). Subsequently, this method was integrated into a pull-wire, flywheel-type, dual-axis centrifugal microfluidic chip, named the Heparin-Inhibited CRISPR-Associated System Chip (HICAS-Chip), enabling integrated enrichment, purification, elution, and multiplexed detection. The HICAS-Chip allowed visual detection of nucleic acids at 10 aM sensitivity within 1 h, corresponding to the sensitivity of the one-pot RT-RPA/CRISPR-Cas12a assay. During a year-long wastewater monitoring program in Guiyang City, China, the HICAS-Chip identified EV-A71 and CV-A10 as the predominant circulating subtypes, with incidence peaks observed in June, November, and December. The wastewater detection results obtained using HICAS-Chip showed high concordance (95.83%) with RT-qPCR assays. This platform provides an efficient portable device for the early detection and continuous monitoring of HFMD epidemic trends by wastewater-based epidemiology.

Dysregulated pulmonary coagulation and inflammation is a hallmark of respiratory failure in various etiologies. Excessive fibrin deposition contributes to alveolar collapse, impaired gas exchange, and progression to pulmonary fibrosis. Nebulized heparin can mitigate these coagulation and inflammation disturbances. Although several randomized controlled trials have explored its effects, results remain inconsistent and limited by small patient populations. We conducted a random-effects meta-analysis to calculate the risk ratio (RR) and 95% CIs. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials comparing nebulized unfractionated heparin to standard care or placebo in adult patients with respiratory failure either invasively mechanical ventilated or not. The primary outcome was all-cause mortality at the longest follow-up. We included randomized clinical trials enrolling adult patients with respiratory failure, comparing nebulized heparin vs. standard care or placebo, and reporting at least one clinical outcome, including all-cause mortality. Two independent investigators extracted data on trial design, setting, etiology of respiratory failure, heparin dosing regimens, follow-up duration, and outcomes. Discrepancies were resolved by consensus. We identified 16 studies (787 receiving nebulized heparin, 833 control). Six (38%) were multicenter, five focused on COVID-19, 12 enrolled ICU patients, and dosing clustered around 25,000 international units (IUs) three times a day (~75,000 IU/d for ~10 d). At the longest follow-up, nebulized heparin reduced all-cause mortality vs. control (110/645 [17.1%] vs. 157/711 [22.1%]; RR, 0.79; 95% CI, 0.66-0.95; with ten studies included). Nebulized heparin was also associated with more ventilation-free days by day 28 (mean difference, +4.85; 95% CI, 1.47-8.24). Major bleeding was rare (1.1 vs. 0.7%; RR, 1.48; 95% CI, 0.42-5.18), while no minor bleeding or heparin-induced thrombocytopenia was reported. Nebulized unfractionated heparin may improve survival in patients with respiratory failure without increasing adverse events.

We present the case of a 74-year-old woman with a large ovarian tumor who developed cancer-associated stroke with multiple acute cerebral infarcts and markedly elevated D-dimer levels. Unfractionated heparin was initiated. However, thrombocytopenia and rising D-dimer levels on Day 11 led to its discontinuation and a diagnosis of probable heparin-induced thrombocytopenia, supported by a strongly positive PF4/heparin antibody assay. Despite subsequent non-heparin anticoagulation, she developed recurrent ischemic stroke and systemic embolic events, and surgery for the ovarian tumor was no longer feasible. This case highlights the therapeutic dilemma posed by the coexistence of cancer-associated stroke and immune-mediated heparin-induced thrombocytopenia.

Pharmacologic thromboprophylaxis is widely used for medical inpatients, but its contemporary benefits remain uncertain for clinically relevant venous thromboembolism (VTE). To evaluate and compare the benefits and risks associated with currently approved in-hospital pharmacologic thromboprophylaxis regimens to prevent symptomatic and clinically relevant VTE and bleeding in acutely ill medical inpatients. MEDLINE, Embase, Web of Science, and the Cochrane CENTRAL databases were searched until January 31, 2026. Reference lists from retrieved articles and reference literature were also examined. Randomized clinical trials that involved adult patients hospitalized for an acute medical illness and compared pharmacologic thromboprophylaxis regimens (low-molecular-weight heparin [LMWH], unfractionated heparin [UHF], and direct oral anticoagulants [DOACs]) with no treatment or placebo were selected. Dual independent screening, data extraction, and risk-of-bias assessment were performed. Relative risks (RRs) were pooled using network meta-analyses with random effects. The PRISMA reporting guideline was used. The effectiveness outcomes were the risk of confirmed symptomatic VTE, clinically relevant VTE, and any VTE. Safety outcomes were mortality, major bleeding, and clinically relevant nonmajor bleeding. Pairwise and network meta-analyses were computed. Among the 22 studies (involving 43 840 patients) included, the 90-day pooled risk of symptomatic VTE was 1.7% (95% CI, 0.6%-4.4%) in the no-treatment group. Compared with no treatment, LMWH was associated with reduced symptomatic VTE risk (RR, 0.68; 95% CI, 0.49-0.94). Point estimates for DOACs (RR, 0.69; 95% CI, 0.36-1.31) and UFH (RR, 0.75; 95% CI, 0.40-1.40) were less than 1, although the results were not statistically significant. LMWH (RR, 0.57; 95% CI, 0.43-0.74), DOACs (RR, 0.58; 95% CI, 0.41-0.82), and UFH (RR, 0.66; 95% CI, 0.45-0.97) were associated with reduced risk of clinically relevant VTE. Using a theoretical conversion rate of asymptomatic into symptomatic VTE, both LMWH and DOACs were associated with decreased risk of symptomatic VTE (RR, 0.63 [95% CI, 0.48-0.83] and 0.66 [95% CI, 0.44-0.99]). DOACs (RR, 2.62; 95% CI, 1.25-5.49) and UFH (RR, 2.33; 95% CI, 1.13-4.79) were associated with an increased risk of major bleeding, compared with no treatment, while LMWH (RR, 1.23; 95% CI, 0.81-1.85) had no association. Mortality was unaffected by the treatment regimens. In this systematic review and network meta-analysis, DOACs, LMWH, and UFH were associated with reduced clinically relevant VTE in medical inpatients; DOACs and UFH had higher risks of major bleeding than LMWH. Proper selection of patients is critical given the overall low absolute risk of VTE.

Although the latest generation left ventricular assist device (LVAD) HeartMate 3 carries a lower thromboembolic risk than earlier devices, reoperations for early postoperative bleeding remain common. In an effort to reduce early bleeding, we revised our anticoagulation strategy by delaying early heparin bridging. In this single-center retrospective study, we compared two anticoagulation protocols after HeartMate 3 implantation. Under the old protocol, heparin was initiated 24-48 hours after implantation if chest drain output was acceptable. In May 2022, our protocol was revised to withhold unfractionated heparin for greater than or equal to 48 hours after implantation. The primary efficacy endpoint was early (< 30 days) postoperative bleeding requiring reoperation. The primary safety endpoint was early ischemic stroke. We analyzed 193 consecutive patients (106 old protocol, 87 new). The 30 day cumulative incidence of early bleeding requiring reoperation was lower with the new protocol (42.4% vs. 24.1%, p = 0.006). Stroke incidence did not differ significantly (6.6% vs. 8.0%, p = 0.72). Total hospital stay (28 vs. 24 days, p = 0.04) and intensive care unit (ICU) stay (7 vs. 5 days, p = 0.03) were shorter with the new protocol. Delaying heparin initiation beyond 48 hours after HeartMate 3 implantation was associated with reduced early bleeding-related reoperations and shorter ICU and hospital stays, without a significant increase in stroke risk.

BackgroundProfound thrombocytopenia after tirofiban exposure during primary percutaneous coronary intervention (PCI) is rare but clinically important. Causal attribution may be challenging when unfractionated heparin is coadministered, and the relevance of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency remains uncertain.Case PresentationA 34‐year‐old man with known G6PD deficiency presented with an inferior ST‐segment elevation myocardial infarction and underwent primary PCI. He received aspirin, ticagrelor, and unfractionated heparin. Coronary angiography showed multivessel coronary disease with complete occlusion of the mid‐to‐distal right coronary artery and a large thrombus burden. After aspiration thrombectomy and drug‐eluting stent implantation, intracoronary tirofiban (2500 μg bolus), followed by intravenous tirofiban infusion (0.15 μg/kg/min), was administered as bailout antithrombotic therapy. Within 6 h, the platelet count fell from 207 × 109 to 1 × 109/L. Peripheral blood smear showed no platelet clumping or abnormal cells. Sepsis and disseminated intravascular coagulation were not supported by laboratory findings. Heparin‐induced thrombocytopenia was considered highly unlikely because the 4Ts score was 1, reflecting the extremely early onset, absence of new thrombosis, and the presence of a more plausible alternative explanation. The clinical course was therefore most consistent with acute tirofiban‐associated profound thrombocytopenia.Interventions and OutcomesTirofiban and heparin were discontinued immediately, and intravenous immunoglobulin (20 g/day) was administered. The platelet count recovered to 25 × 109/L at 48 h, 48 × 109/L at 72 h, and 124 × 109/L on Day 4. Clopidogrel was restarted at 48 h, followed by indobufen at 72 h. No major bleeding or thrombotic complications occurred.ConclusionsThis case supports tirofiban‐associated acute profound thrombocytopenia as the most likely diagnosis and underscores the importance of prompt drug withdrawal, structured differential diagnosis against heparin‐induced thrombocytopenia, and individualized antithrombotic reinitiation. The contribution of G6PD deficiency remains hypothetical and requires further study.

Patient: Female, 45-year-oldFinal Diagnosis: Pulmonary air embolismSymptoms: Dynpnea • palpitationClinical Procedure: —Specialty: Critical Care Medicine • PulmonologyObjective: Unusual clinical courseBackgroundPulmonary embolism is associated with increased morbidity and mortality, yet the patient can sometimes look deceptively calm at the bedside. A normal blood pressure reading does not rule out a struggling right ventricle, and patients classified as intermediate-high-risk can deteriorate quickly. A mobile right-heart thrombus (clot-in-transit) adds another layer of urgency because embolization can be sudden and unpredictable.Case ReportA 45-year-old woman with a previous pulmonary embolism presented with abrupt dyspnea, tachycardia, and hypoxemia shortly after stopping apixaban. Bedside transthoracic echocardiography showed marked right ventricular dilation and a mobile right atrial thrombus consistent with clot-in-transit. Computed tomography pulmonary angiography confirmed bilateral segmental/subsegmental pulmonary embolism. Although she remained normotensive, biomarker positivity and a lactate rise suggested early hypoperfusion. After immediate anticoagulation with unfractionated heparin, the Pulmonary Embolism Response Team was activated, and, after multidisciplinary discussion, we decided to treat the patient with reduced-dose systemic alteplase (50 mg over 2 hours). The patient improved rapidly without bleeding complications and was discharged on long-term anticoagulation. She remained in excellent clinical condition at her 2-month follow-up.ConclusionsThis case demonstrates that in pulmonary embolism, stability is more than a blood pressure reading. The presence of right ventricular strain together with a clot-in-transit can justify immediate treatment escalation. Reduced-dose systemic thrombolysis can be a reasonable option in carefully selected patients, but decisions should remain individualized.

Floating thrombus of the aortic arch in the absence of aneurysm or atherosclerotic disease is an exceptionally rare condition. We report the case of a 47-year-old woman, an active smoker with iron-de&amp;#64257; ciency anemia, who presented with acute retrosternal chest pain, dyspnea, diaphoresis, and vomiting. Initial evaluation showed arterial hypertension, sinus rhythm with poor R-wave progression in the precordial leads on electrocardiography (ECG), and markedly elevated high-sensitivity troponin levels, consistent with acute coronary syndrome. Transthoracic echocardiography (&amp;#1058;&amp;#1058;&amp;#1045;) revealed a large, highly mobile mass in the aortic arch prolapsing into the supra-aortic branches, reduced left ventricular systolic function and apical dyskinesia. Computed tomography angiography (CTA) con&amp;#64257; rmed a &amp;#64258; oating thrombus attached to the lesser curvature of the aortic arch, mild non-obstructive coronary artery disease, and an apical left ventricular aneurysm. The patient was initially managed conservatively with unfractionated heparin and aspirin due to high procedural risk. However, despite therapeutic anticoagulation, she developed a transient cerebrovascular event, prompting urgent surgical intervention. Intraoperatively, a loosely attached mixed thrombus was excised from the aortic arch without evidence of atherosclerosis or endothelial injury. The postoperative course was uneventful. This case emphasizes the high embolic potential of &amp;#64258; oating aortic arch thrombi and supports early surgical consideration when embolic complications occur despite optimal anticoagulation.

Antiphospholipid syndrome (APS) is an autoimmune disease defined by thrombotic or obstetrical clinical manifestations and the persistent presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein 1 antibodies. Obstetric APS (OAPS) is associated with pregnancy morbidity, including early recurrent pregnancy loss (RPL), preeclampsia, premature birth and stillbirth. Treatment regimens for women with OAPS are designed to optimise pregnancy outcomes. It is still debated which intervention results in the most optimal pregnancy outcome. This scoping review examines treatment options for women with OAPS presenting with RPL based solely on randomized controlled trials (RCTs) reporting pregnancy outcomes. A systematic search identified 1,234 studies published up to January 2026, from which 14 RCTs met the inclusion criteria: pregnant women with APS defined as persistent aPL positivity and RPL (≥2) receiving therapeutic intervention with live birth as the primary outcome. These RCTs, published between 1992 and 2017, included 1,878 participants. Secondary outcomes, including birth weight, preeclampsia, preterm delivery, and bleeding were also analyzed. Different treatment options such as low-dose aspirin (LDA), unfractionated heparin, low molecular weight heparin (LMWH), corticosteroids and intravenous immunoglobulin were used in the clinical trials. Antithrombotic therapy (LDA+LMWH) was associated with higher live birth rates compared with the other evaluated strategies. However, this finding is based on a small number of heterogeneous RCTs and is disproportionately driven by a single large trial. Consequently, substantial uncertainty remains. High-quality, adequately powered RCTs are urgently needed to provide robust evidence for optimal OAPS management.

Heparin resistance (HR) poses the risk for significant complications, as subtherapeutic anticoagulation may lead to thrombotic events; however, there remains a lack of guidance on standardized management strategies in cardiac intensive care unit (CICU) patients and those with mechanical circulatory support (MCS) devices. The purpose of this study is to describe current management strategies for patients with suspected HR and provide insights into its definition among critically ill cardiac patients. This retrospective study evaluated intensive care unit (ICU) patients receiving greater than or equal to 25 units/kg/h of unfractionated heparin (UFH) that failed to achieve 2 consecutive therapeutic activated partial thromboplastin time (aPTT) values. The primary outcome was incidence of patients transitioned to a direct thrombin inhibitor (DTI). Secondary outcomes included major bleeding, thrombosis, and antithrombin III supplementation. A subgroup analysis compared anticoagulation characteristics by agent (UFH vs. DTI), including anticoagulant infusion volume, and time to goal aPTT. Of 76 patients receiving titratable UFH, 62 (81.6%) met inclusion criteria. Transition to a DTI occurred in 4 (6.5%) patients, all who received bivalirudin. Major bleeding occurred in 4 (6.5%) patients and thrombosis in 2 (3.2%) while receiving UFH. Median time to goal aPTT was 88 (interquartile range [IQR] = 55.3-123.3) hours with UFH vs. 6 (IQR = 3.7-11.3) hours with bivalirudin (P = 0.002). Median daily anticoagulant volume was 578 (IQR = 404.0-770.4) mL with UFH vs. 190 (IQR = 147.3-218.5) mL with bivalirudin (P = 0.001). Our findings describe current management practices for suspected HR among critically ill cardiac patients. Although the small subset of patients transitioned to DTI limits generalizability, earlier recognition and individualized anticoagulation strategies may be warranted in MCS patients given their inherent thrombotic risk. Future studies are needed to further define HR and evaluate anticoagulation strategies in this population.

Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking. We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin. This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.

Lung Injury after Supraceliac Aortic Cross-Clamping: No Benefit from Unfractionated Heparin in Rats.

Anticoagulation is used in intensive care medicine to prevent and treat thromboembolism. The increased risk of bleeding in this patient population requires apersonalized approach to management including individualized anticoagulant selection and dose adjustment. While low-molecular-weight heparins are equivalent or superior to unfractionated heparin for thromboprophylaxis, unfractionated heparin is the preferred therapy for the treatment of thromboembolism. Its advantages include arelatively short half-life, the ability to monitor therapy using the activated partial thromboplastin time and the possibility of rapid and effective reversal. The direct thrombin inhibitor argatroban is areserve anticoagulant used to treat patients with heparin-induced thrombocytopenia. The advantages of argatroban are its short half-life, hepatic clearance, and the ability to monitor therapeutic levels using the activated partial thromboplastin time.

Although cerebral venous thrombosis (CVT) has been widely studied in general clinical contexts, its occurrence after brain surgery raises specific concerns. CVT is a rare complication that may arise from sinus injury during brain surgery and is now increasingly recognized, due to frequent post-surgery imaging studies. There is also controversy over antithrombotic treatment in the acute phase. This narrative review analyzes the published literature on CVT in patients who underwent brain surgery, with a particular focus on diagnosis and therapeutic management. A PubMed search was conducted for articles published between 2014 and 2025. After title, abstract, and full-text screening, 32 studies were included. CVT after brain surgery is often asymptomatic and detected on routine postoperative imaging, but it should be suspected in the presence of symptoms of intracranial hypertension, seizures, or even delayed anesthesia recovery. Diagnosis relies primarily on plain CT or MRI plus CT or MR venography, with thrombophilia screening indicated when surgery alone does not justify sinus injury. Parenteral anticoagulation is the first-line treatment. Unfractionated heparin may be preferred over low molecular weight heparin in the first days after diagnosis because its effect is easier to reverse in case of emergency. Endovascular therapy may be considered in high-risk (large hemorrhage) or refractory cases. Intraoperatively, preventive measures include minimizing sinus injury and ensuring adequate hydration. Postoperative prophylactic anticoagulation should be considered in patients with known prothrombotic factors, weighing the thrombotic versus hemorrhagic risk. Overall, prognosis appears favorable, though evidence remains limited. CVT after brain surgery is rare and its management should be decided accordingly to the clinical particularities of each case. Evidence is limited and often extrapolated from general populations, highlighting the need for targeted research to improve outcomes and guide treatment decisions.

The dual antiplatelet and anticoagulant (APAC), a heparin proteoglycan mimetic, targets vascular injury sites and alleviates thromboinflammation in models of atherosclerosis and acute ischemic reperfusion injury. Here, we establish that APAC also modulates the complement system activation. Complement activity was assessed by pathway-specific enzyme-linked immunosorbent assays. APAC-anticoagulated blood was assessed by intrinsic coagulation pathway (intrinsic pathway-activated rotational thromboelastometry [InTEM]), and APAC-plasma by prothrombin fragments 1 and 2. Interactions of APAC-biotin with serum complement components were detected by pulldown and liquid chromatography-mass spectrometry analysis. The surface effect of APAC was studied with zymosan and on THP-1 cell line-derived apoptotic and necrotic cells. Comparisons were made to unfractionated heparin (UFH). Both serum spike-in and donor APAC-plasma studies showed that APAC reduces systemic complement activity similarly to UFH, except for the classical pathway, which APAC inhibited more prominently. The effective concentration range of APAC was 30 to 100 μg/mL. In APAC-plasma, InTEM was inhibited and thrombin generation was delayed at >30 μg/mL of APAC. In APAC pulldown and in vitro complement activation tests, APAC specifically interacted with necrotic cells and recruited C1q and factor H (FH) onto the cell surfaces. Importantly, APAC promoted early complement activation at the C3 level on cell surfaces, without proportional terminal pathway (C5b-9) activation. APAC interacts with several complement components without adversely affecting systemic complement activity within the expected therapeutic range. APAC may regulate complement activation on cell surfaces even at subinhibitory concentrations, promoting early complement activation via C1q but limiting it to the level of C3 by recruiting FH.