Increased white blood cell count is associated with an increased demand for unfractionated heparin during veno-arterial extracorporeal oxygenation in lung transplantation.

BACKGROUND: This retrospective observational study aimed to examine whether clinical inflammatory parameters were associated with the requirement dosage of unfractionated heparin (UFH) to maintain the range of ACT in veno-arterial extracorporeal membrane oxygenation (V-A ECMO) during lung transplantation surgery. METHODS: Among all patients who underwent lung transplantation using V-A ECMO from January 2021 to May 2022, 27 patients were included. These patients were divided into two groups based on whether the infusion rate of UFH was increased from the initial infusion rate (7-8 units/kg/h) (increased group, n = 10) or the infusion rate was maintained or decreased (non-increased group, n = 17). The infusion rate was adjusted with an activated clotting time (ACT) target of 160-200 s. RESULTS: At 1-2 h after starting ECMO, ACT was significantly lower (179.0 (166.5-188.5) versus 224.0 (193.0-242.0) sec, p = 0.006) and white blood cell (WBC) counts were higher in the increased group (12.6 ± 3.3 versus 9.5 ± 4.0 × 103/µL, p = 0.046). The UFH infusion rates were higher in the increased group during the surgery. The cutoff value of WBC count at 1-2 h after starting ECMO for discriminating the need for increasing the UFH dosage was determined as 10.2 × 103/µL (sensitivity 90.0%, specificity 58.8%, area under the curve 0.712) and discrimination of this cut-off value was confirmed as statistically significant (p = 0.018). CONCLUSION: These data suggested that WBC count was associated with the requirement of an increase in the UFH infusion rate of V-A ECMO during lung transplantation surgery. Further evaluation is necessary to clarify the role of WBC count in determining the optimal UFH dosage.

Heparin resistance management during cardiac surgery: a literature review and future directions.

INTRODUCTION: Heparin, a commonly used anticoagulant in cardiac surgery, binds to antithrombin III (ATIII) to prevent clot formation. However, heparin resistance (HR) can complicate surgical procedures, leading to increased thromboembolic risks and bleeding complications. Proper diagnosis and management of HR are essential for optimizing surgical outcomes. METHODOLOGY: Diagnosis of HR involves assessing activated clotting time (ACT) and HR assays. Management strategies were identified through a comprehensive review of the literature, including studies exploring heparin dosage adjustments, antithrombin supplementation, and alternative anticoagulants in cardiac surgery patients with HR. A thorough search of relevant studies on HR was conducted using multiple scholarly databases and relevant keywords, resulting in 59 studies that met the inclusion criteria. DISCUSSION: HR occurs when patients do not respond adequately to heparin therapy, requiring higher doses or alternative anticoagulants. Mechanisms of HR include AT III deficiency, PF4 interference, and accelerated heparin clearance. Diagnosis involves assessing ACT and HR assays. HR in cardiac surgery can lead to thromboembolic events, increased bleeding, prolonged hospital stays, and elevated healthcare costs. Management strategies include adjusting heparin dosage, supplementing antithrombin levels, and considering alternative anticoagulants. Multidisciplinary management of HR involves collaboration among various specialities. Strategies include additional heparin doses, fresh frozen plasma (FFP) administration, and antithrombin concentrate supplementation. Emerging alternatives to heparin, such as direct thrombin inhibitors and nafamostat mesilate, are also being explored. CONCLUSION: Optimizing the management of HR is crucial for improving surgical outcomes and reducing complications in cardiac surgery patients. Multidisciplinary approaches and emerging anticoagulation strategies hold promise for addressing this challenge effectively.

A case of the effective inhalation of nitric oxide therapy for caused severe pulmonary hypertension with protamine neutralization of systemic heparinization during totally endoscopic minimally invasive cardiac surgery.

Severe pulmonary vasoconstriction induced by protamine is a rare complication. We report a case of a 77-year-old male patient with a history of mitral valve plasty (MVP). He underwent redo MVP via right thoracotomy under the totally endoscopic procedure (MICS redo-MVP). Immediately after weaning cardiopulmonary bypass (CPB), protamine was administrated. 10 min later peak systolic pulmonary arterial pressure (sys PAP) rose to 62 mmHg, and 30 min later to 80 mmHg. Due to the negative impact of protamine administration, nitric oxide inhalation (iNO) therapy was started with a concentration of 20 ppm. 10 min after iNO therapy started, sys PAP decreased to 63 mmHg. After entering the intensive care unit (ICU), sys PAP decreased to 35 mmHg. Here, we present an effective iNO therapy case for pulmonary hypertension due to protamine and the patient had a good postoperative recovery. This study was approved by the Institutional Review Board at Kitaharima Medical Center (IRB-0602) with the waiver of informed consent.

Assessment of the effect of unfractionated heparin administered either by intravenous infusion vs. subcutaneous injection on heparin-binding protein, and plasminogen activator inhibitor-1 in critically ill septic patients: a randomized controlled trial.

OBJECTIVE: The study compared the impact of unfractionated heparin (UFH) administered via two routes (infusion and subcutaneous injection) on heparin-binding protein (HBP) and plasminogen activator inhibitor-1 (PAI-1) levels in critically ill sepsis patients. PATIENTS AND METHODS: Forty critically ill sepsis patients were randomly assigned to receive either a low-dose intravenous infusion of UFH (500 units/hour) or subcutaneous UFH (5,000 units/8 hours) for seven days. HBP and PAI-1 were measured at baseline and on days one, two, and seven. RESULTS: Intravenous administration of UFH showed a significant reduction in percentage change of HBP compared to subcutaneous administration on days one [(-35% vs. -13%, p = 0.03*) (*indicates a significant result *p < 0.05, relative to the subcutaneous group)] and seven (-62% vs. -39%, p = 0.02*). Also, the percentage change of PAI-1 was significantly reduced in the infusion group compared to the subcutaneous group on days one (-28% vs. -3%, p = 0.008*), two (-42% vs. -3%, p = 0.001*), and seven (-62% vs. 27%, p = 0.001*), respectively. Furthermore, a significant improvement in the 14-day survival was observed in the infusion group compared to the subcutaneous group (p = 0.008*). CONCLUSIONS: Intravenous infusion was the route of choice for UFH administration in critically ill septic patients, with a promising effect on HBP, PAI-1, and survival.

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial.

BACKGROUND: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use. METHODS: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. RESULTS: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; Pinteraction = 0.07) or its individual components between bivalirudin and heparin groups. CONCLUSIONS: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03822975.

Switching from acetate to citrate dialysate in a central concentrate delivery system for high-volume online hemodiafiltration: a retrospective cohort study.

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.

Management of iatrogenic acute limb ischaemia in the neonate.

Iatrogenic acute limb ischaemia (ALI) in neonates is a rare but severe event with potentially deleterious outcomes. In the neonatal intensive care unit, this risk is increased due to the high rate of catheterisation procedures. ALI management includes pharmacological and non-pharmacological interventions, but no commonly accepted clinical guidelines are available. In the present case, a peripheral catheter was erroneously placed in the left brachial artery of a term infant, causing blockage and ischaemia in the limb. The catheter was immediately removed, the affected limb was elevated and warm compresses were applied to the contralateral limb. The patient was treated with fresh frozen plasma, heparin, iloprost and topical nitroglycerin. Three nerve block procedures were also performed. At 6-8 days of age, significant improvement was observed. The patient was discharged at 17 days of age with near-complete resolution, whereas complete resolution was observed at postdischarge follow-up.

Antithrombotic Therapy in Patients with Complex Percutaneous Coronary Intervention and Cardiogenic Shock.

Managing antithrombotic therapy in patients undergoing complex and high-risk in indicated patients, including those treated with complex percutaneous coronary intervention (PCI) or presenting with cardiogenic shock (CS), is challenging. This review highlights the critical role of antithrombotic therapy, during and after PCI, to optimize the efficacy while minimizing risks. Unfractionated heparin remains the mainstay anticoagulant for complex PCI and CS, with bivalirudin as a potential safer alternative. Cangrelor offers consistent antiplatelet effects, especially when timely absorption of oral agents is uncertain.

Inadequate anticoagulation and hyperuricemia cause knee pain after platelet-rich plasma injection: A retrospective study.

OBJECTIVES: Platelet-rich plasma treatment delays the need for total knee replacement in patients with knee osteoarthritis. However, its use and preparation remain controversial. The aim of this study was to investigate the relationship between anticoagulant use in the preparation of platelet-rich plasma and post-treatment pain in patients with knee osteoarthritis. Additionally, we explored the efficacy of platelet-rich plasma over medium- and long-term follow-up periods and identified other factors that may affect treatment outcomes. METHODS: In this retrospective study, 225 patients with knee osteoarthritis, who underwent knee platelet-rich plasma treatment from June 2021 to January 2022, were examined at three study centres. Patients were categorised, based on the type and amount of anticoagulant used during platelet-rich plasma preparation, into 4% sodium citrate (SC) 0.6 mL, 4% SC 1 mL, 4% SC 2 mL, heparin 0.1 mL, and heparin 0.2 mL groups. We analysed the patients' basic information, pain after treatment, and inflammatory markers (i.e., interleukin 6, tumour necrosis factor-α, and hypersensitive C-reactive protein) in the joint fluid via enzyme-linked immunosorbent assay and joint fluid crystallisation. Additionally, we assessed the patients' Western Ontario and McMaster University scores and minimal clinically significant differences after treatment. RESULTS: Patients in the 4% SC 0.6 mL and heparin 0.1 mL groups experienced less pain after platelet-rich plasma treatment than did patients in the high-dose anticoagulant group. The joint fluid of patients with pain in these groups had lower levels of inflammatory markers. Patients treated with SC had slightly better medium- and long-term therapeutic outcomes than did patients treated with heparin. Patients with poorly controlled hyperuricemia also experienced pain after platelet-rich plasma treatment. CONCLUSIONS: The results suggest that platelet-rich plasma prepared using high-dose anticoagulants or administered to patients with poorly controlled hyperuricaemia may lead to moderate-to-severe knee pain and joint effusion after joint puncture therapy. Platelet-rich plasma had a therapeutic effect on knee osteoarthritis; however, its efficacy gradually decreased over time. SC anticoagulant is more suitable for platelet-rich plasma preparation than is heparin. Further studies are needed to understand the safety and the various factors influencing platelet-rich plasma therapy.

The impact of early perioperative heparin-free anticoagulation for extracorporeal membrane oxygenation on bleeding and thrombotic events in lung transplantation: a retrospective cohort study.

BACKGROUND: Perioperative heparin-free anticoagulation extracorporeal membrane oxygenation (ECMO) for lung transplantation is rarely reported. OBJECTIVE: To evaluate the impact of a heparin-free strategy on bleeding and thrombotic events, blood transfusion, and coagulation function during the early perioperative period and on prognosis, and to observe its effect on different ECMO types. DESIGN: A retrospective cohort study. METHODS: Data were collected from 324 lung transplantation patients undergoing early perioperative heparin-free ECMO between August 2017 and July 2022. Clinical data including perioperative bleeding and thrombotic events, blood product transfusion, coagulation indicators and 1-year survival were analysed. RESULTS: Patients were divided in venovenous (VV; n = 251), venoarterial (VA; n = 40) and venovenous-arterial (VV-A; n = 33) groups. The VV group had the lowest intraoperative bleeding and thoracic drainage within 24 h postoperatively. Vein thrombosis occurred in 30.2% of patients within 10 days postoperatively or 1 week after ECMO withdrawal, and no significant difference was found among the three groups. Double lung transplantation, increased intraoperative bleeding, and increased postoperative drainage were associated with vein thrombosis. Except for acute myocardial infarction in one patient, no other serious thrombotic events occurred. The VV-ECMO group had the lowest demand for blood transfusion. The highest prothrombin time and the lowest fibrinogen levels were observed in the VA group during ECMO run, while the highest platelet counts were found in the VV group. Both intraoperative bleeding and thoracic drainage within 24 h postoperatively were independent predictors for 1-year survival, and no thrombosis-related deaths occurred. CONCLUSION: Short-term heparin-free anticoagulation, particularly VV-ECMO, did not result in serious thrombotic events or thrombosis-related deaths, indicating that it is a safe and feasible strategy for perioperative ECMO in lung transplantation.

Hemodialysis without Systemic Anticoagulation: A Randomized Controlled Trial to Evaluate Five Strategies in Patients at a High Risk of Bleeding.

BACKGROUND: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach. AIM: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis. METHODS: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions. PRIMARY ENDPOINT: the successful completion of hemodialysis without clotting. SECONDARY OUTCOMES: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions. RESULTS: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed. CONCLUSIONS: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Safety and efficacy of drug-eluting stents versus heparin-bonded stents in treatment of femoropopliteal peripheral artery disease: study protocol for a multicentre, prospective randomised controlled trial in China (ELITE trial).

INTRODUCTION: Endovascular therapy has emerged as a prominent strategy for managing femoropopliteal peripheral artery disease, offering acceptable safety and efficacy compared with open surgical bypass. Both paclitaxel-eluting stents and heparin-bonded covered stents have exhibited enhanced clinical outcomes compared with bare metal stents. However, there is currently a lack of level I evidence comparing the safety and efficacy of paclitaxel-eluting stents and heparin-bonded covered stents. Therefore, the primary objective of this study is to systematically evaluate the efficacy and safety outcomes of these two types of stents. METHODS AND ANALYSIS: The ELITE trial is a prospective, multicentre, parallel, randomised controlled trial. A total of 450 patients will be recruited. The primary endpoints of the study include primary patency at 1 year post-index procedure. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Ethics Committee of West China Hospital of Sichuan University (approval number: 2023-1186). The results will be submitted to a major clinical journal for peer review and publication. TRIAL REGISTRATION: ELITE trial was registered on 27 September 2023 in the Chinese Clinical Trials Registry (ChiCTR2300076236).

Peri-operative Anticoagulation Strategies, Bleeding and Thrombotic Complications in Pediatric Patients Undergoing Intervention for Congenital Portosystemic Shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications. METHODS: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications. RESULTS: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported. CONCLUSIONS: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively. LEVELS OF EVIDENCE: Level II, retrospective study.

Intravenous injection of nattokinase-heparin electrostatic complex improves the therapeutic effect of advanced tumors by dissolving cancer-related thrombosis.

AIMS: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors. MAIN METHODS: In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors. KEY FINDINGS: We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer. SIGNIFICANCE: This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy.

The CATERPILLAR study: an assessor-blinded randomized controlled trial comparing a taurolidine-citrate-heparin lock solution to a heparin-only lock solution for the prevention of central-line-associated bloodstream infections in paediatric oncology patients.

BACKGROUND: Taurolidine-citrate(-heparin) lock solutions (TCHL) are suggested as a promising and safe method for the prevention of central-line-associated bloodstream infections (CLABSI). AIM: To investigate the efficacy of TCHL for the prevention of CLABSI in paediatric oncology patients. METHODS: An assessor-blinded randomized controlled trial at the Princess Máxima Centre for paediatric oncology, the Netherlands, was performed from 2020 to 2023. Paediatric oncology patients receiving a tunnelled central venous access device (CVAD) were eligible. A total of 462 patients were required to compare the TCHL to the heparin-only lock (HL). Patients were followed-up for the first 90 days after CVAD insertion. The primary outcome was the incidence of the first CLABSI from CVAD insertion until the end of follow-up. Intention-to-treat and per-protocol analyses were performed. FINDINGS: In total, 232 were randomized in the HL and 231 in the TCHL group. A total of 47 CLABSIs were observed. The intention-to-treat analysis showed that a CLABSI was observed in 26 (11.2%) of the HL group patients versus 21 (9.1%) of the TCHL group patients; incidence rate ratio (IRR) of 0.81 (95% confidence interval (CI): 0.46-1.45) in favour of the TCHL group. The per-protocol analysis showed that a CLABSI was observed in 10 (7.9%) of the HL group patients versus 6 (4.8%) of the TCHL group patients; IRR of 0.59 (95% CI: 0.21-1.62) in favour of the TCHL group. Adverse events were more common in the TCHL group but rarely reported. CONCLUSION: No difference was detected between the TCHL and HL in the incidence of CLABSI in paediatric oncology patients.

Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study.

BACKGROUND: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking. OBJECTIVES: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻1, tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications. METHODS: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻1 receiving prophylactic (4500 IU.d⁻1) or therapeutic (175 IU.kg⁻1.d⁻1) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates. RESULTS: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻1, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications. CONCLUSION: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment.

Factors influencing circuit lifetime in paediatric continuous kidney replacement therapies - results from the EurAKId registry.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children. METHODS: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications. RESULTS: The analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37-165 h per patient). A total of 1357 circuits were utilised (3, IQR 2-6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient's age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications. CONCLUSION: Anticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT.

Initial Experience with the Derivo 2Heal Flow Diverter under Standard or Reduced-Dose Single Antiplatelet Therapy.

BACKGROUND AND PURPOSE: Flow diverters with surface modifications or coatings have been recently introduced to clinical practice with the expectation that they can reduce the rate of thromboembolic complications and residual aneurysms. The purpose of this study is to evaluate the utility of the Derivo 2Heal (D2H) device, a new fibrin and heparin-coated flow diverter. MATERIALS AND METHODS: Patients treated by a single operator by using the D2H were retrospectively evaluated for demographic data, aneurysm characteristics, procedural variables, and follow-up data. All patients were treated by using a single D2H, monitored by platelet function testing and kept under single antiplatelet therapy with regular or half-dose clopidogrel or prasugrel after the procedure. RESULTS: Twenty patients with 26 aneurysms were treated. Three presented acutely with subarachnoid hemorrhage. Adjunctive devices were used in 6 patients. There were no technical failures and 2 periprocedural self-limited nonthrombotic minor adverse events. During follow-up, 1 of the acutely ruptured aneurysms reruptured, and 1 patient had a visual TIA. All patients were doing well clinically (19 with mRS of 0 and 1 with 1) at the last follow-up after discharge. The rates of total occlusion on very early angiographic (MRA/CTA or DSA, mean: 2.4 months), DSA (mean: 5.8 months), and midterm angiographic (mean: 14.5 months) follow-up for all versus uncoiled aneurysms were 68% versus 70%, 77.8% versus 90.0%, and 91.7% versus 90.1%, respectively. CONCLUSIONS: The absence of permanent neurologic deficits in the periprocedural period and favorable occlusion rates in this preliminary study suggest that the novel coating comprising fibrin and heparin may have the potential to increase the safety and efficacy of flow diversion and needs to be further studied by comparing the D2H device with its bare counterpart and other coated or surface-modified flow diverters.