Use of heparinized saline flush during endovascular thrombectomy for acute ischemic stroke; a survey of clinical practice in the Netherlands

Background and introduction Information about optimal use of heparin in flush fluids during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) is lacking. Variables that determine total heparin dose entering the patient by flush fluids are mostly unknown. We aim to provide insight in these unknown but highly relevant variables. Methods and results We performed a survey including all Dutch interventionists performing EVT (n = 79) collecting data on used concentration of heparin in infusion bags, number of infusion bags connected, timing of connecting the flush line and the dripping rate (ml/sec). We calculated potential heparin dose entering the patient per hour through flush fluids (IU/h). Twenty-eight interventionists (35%) representing 17 Dutch stroke centers completed the survey. Eight interventionists responded not to add any heparin to flush fluids (18%). The highest amount of heparin entering the patients was 13,500 IU/h, reported by 2 interventionists from the same center (4%). Conclusions We provide insight in the use of heparinized flush during EVT in the Netherlands. Total amounts of heparin administered via flush fluids may go up to 13,500 IU/h. With this paper we intend to set a starting for future research and development of guidelines on the use of heparinized flush fluids during EVT for AIS.

Assessing Anticoagulation in Neonates With Congenital Diaphragmatic Hernia During Extracorporeal Membrane Oxygenation: Does Anti-Factor Xa or Thromboelastometry Provide Additional Benefit?

Objective: The optimal management of anticoagulation in neonatal/pediatric patients during extracorporeal membrane oxygenation (ECMO) has not been established yet and varies greatly among ECMO centers worldwide. Therefore, we aimed to assess whether the use of anti-factor Xa assay and/or thromboelastometry correlate better than activated clotting time with heparin dose in newborns with congenital diaphragmatic hernia during ECMO. We also examined whether these coagulation assays correlate with thrombotic and/or hemorrhagic complications, when the management of anticoagulation is based only on activated clotting time values.Methods: A prospective observational study in a neonatal ECMO center was conducted. We included all neonates with congenital diaphragmatic hernia born in our institution between March 2018 and January 2019 and requiring support with venoarterial ECMO. A total of 26 ECMO runs were analyzed. During the study, the heparin dose was still adjusted according to activated clotting time values. Measurements of anti-factor Xa assay, activated partial thromboplastin time, and a thromboelastometry from the same blood specimen were performed twice a day.Results: Anti-factor Xa levels showed a moderate correlation with heparin dose, whereas the other tests showed a weak correlation. Four patients (17.4%) had thrombotic complications, 2 patients (8.7%) experienced life-threatening bleeding, and in 11 patients (47.8%) disseminated intravascular coagulation (DIC) occurred. Anti-factor Xa levels were lower in the group with thrombotic complications (0.23 vs. 0.27 IU/ml; p = 0.002), while activated partial thromboplastin time was higher in the group with hemorrhagic complications (69.4 s vs. 59.8 s; p = 0.01). In patients experiencing DIC, heparin dose and anti-factor Xa levels were lower, while no difference in activated clotting time and clotting time in INTEM and INTEM-HEPTEM were shown.Conclusions: Anti-factor Xa levels correlate better to heparin dose than activated clotting time. The use of anti-factor Xa assay instead of activated clotting time for dosing of unfractionated heparin could reduce thrombotic complications in neonates with congenital diaphragmatic hernia on ECMO support. The thromboelastometry showed no additional benefit for this purpose.

Prevention of Venous Thromboembolism in Microvascular Surgery Patients Using Weight-Based Unfractionated Heparin Infusions

Background Unfractionated heparin infusions are commonly used in microvascular surgery to prevent microvascular thrombosis. Previously, fixed-dose heparin infusions were believed to provide sufficient venous thromboembolism (VTE) prophylaxis; however, we now know that this practice is inadequate for the majority of patients. Anti-factor Xa (aFXa) level is a measure of unfractionated heparin efficacy and safety. This study evaluated the pharmacodynamics of weight-based dose heparin infusions and the impacts of real-time aFXa-guided heparin dose adjustments. Methods This prospective clinical trial enrolled adult microvascular surgery patients who received a weight-based heparin dose following a microsurgical procedure. Steady-state aFXa levels were monitored, and patients with out-of-range levels received dose adjustments. The study outcomes assessed were aFXa levels at a dose of heparin 10 units/kg/hour, time to adequate aFXa level, number of dose adjustments required to reach in-range aFXa levels, and clinically relevant bleeding and VTE at 90 days. Results Twenty-one patients were prospectively recruited, and usable data were available for twenty patients. Four of twenty patients (20%) had adequate prophylaxis at a heparin dose of 10 units/kg/hour. Among patients who received dose adjustments and achieved in-range aFXa levels, the median number of dose adjustments was 2 and the median weight-based dose was 11 units/kg/hour. The percentage of patients with in-range levels was significantly increased (65 vs. 15%, p = 0.0002) as a result of real-time dose adjustments. The rate of VTE at 90 days was 0%, and clinically relevant bleeding rate at 90 days was 15%. Conclusion Weight-based heparin infusions at a rate of 10 units/kg/hour provide a detectable level of anticoagulation for some patients following microsurgical procedures, but most patients require dose adjustment to ensure adequate VTE prophylaxis.

The impact of oral direct thrombin inhibitors on activated clotting time during catheter ablation in patients with atrial fibrillation

Funding Acknowledgements Type of funding sources: None. Background Direct thrombin inhibitors (DTIs) unlike factor Xa-inhibitors (Xa-inhibitors) is associated with fewer bleeding complications than warfarin in patients who had catheter ablation (CA) for atrial fibrillation (AF). However, the mechanisms remains unclear, and activated clotting time (ACT) is used to control heparin-dose for thromboembolic prevention during CA. Methods: We retrospectively studied 543 patients taking direct oral anticoagulant (DOAC) who underwent CA for AF (375 males, age 67 ± 10, 251 non-paroxysmal AF, 142 DTIs). Patients with off-label usage of DOAC were excluded. ACT was measured before (Pre-ACT) and after (post-ACT) initial heparin administration (3000U + 100U/kg), and total heparin-dose was evaluated. Results: Pre-ACT and post-ACT were extended in patients with DTIs (150 ± 21 vs 123 ± 15; P < 0.0001 and 322 ± 39 vs 309 ± 42 sec; P = 0.0013). Patients with Xa-inhibitors required higher total heparin-dose (199 ± 43 vs 175 ± 34 U/kg; P < 0.0001). During and after CA, none had thromboembolic events and 14 patients (3 DTIs, 11 Xa-inhibitor) showed bleeding events (Figure). Conclusions: ACT is extended in patients taking DTIs. Xa-inhibitors might have anticoagulant effects which are not reflected in ACT. Abstract Figure.

Decreased CRRT Filter Lifespan in COVID-19 ICU Patients

(1) Background: Increased thromboembolic events and an increased need for continuous renal replacement therapy (CRRT) have been frequently reported in COVID-19 patients. Our aim was to investigate CRRT filter lifespan in intensive care unit (ICU) COVID-19 patients. (2) Methods: We compared CRRT adjusted circuit lifespan in COVID-19 patients admitted for SARS-CoV-2 infection to a control group of patients admitted for septic shock of pulmonary origin other than COVID-19. Both groups underwent at least one session of CRRT for AKI. (3) Results: Twenty-six patients (13 in each group) were included. We analysed 117 CRRT circuits (80 in the COVID-19 group and 37 in the control group). The adjusted filter lifespan was shorter in the COVID-19 group (17 vs. 39 h, p < 0.001). This trend persisted after adjustment for confounding factors (−14 h, p = 0.037). Before CRRT circuit clotting, the COVID-19 group had a more procoagulant profile despite higher heparin infusion rates. Furthermore, we reported a decreased relation between activated partial thromboplastin time (aPTT) and cumulative heparin dose in COVID-19 patients when compared to historical data of 23,058 patients, suggesting a heparin resistance. (4) Conclusion: COVID-19 patients displayed a shorter CRRT filter lifespan that could be related to a procoagulant profile and heparin resistance.

Hemostasis, coagulation and thrombin in venoarterial and venovenous extracorporeal membrane oxygenation: the HECTIC study

Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand’s activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500–24000] versus VV 28,800 IU [IQR 17,300–40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.

Coronary angioplasty and COVID-19: are heparin requirements and thrombotic complications increasing?

Funding Acknowledgements Type of funding sources: None. Background Covid-19 infection is associated with coagulopathy and possible heparin resistance, raising concerns that routine heparin during percutaneous coronary intervention (PCI) is failing to achieve adequate anticoagulation. We examined heparin requirements and efficacy in patients treated by PCI before and after the first reported UK case of Covid-19 (January 31st 2020). Methods We retrospectively compared heparin dose, Activated Clotting Time (ACT) and coronary flow (TIMI grade) for PCI procedures at a London cardiac centre in the 3 months before the UK pandemic and the three months afterwards. Testing for COVID was not routinely performed. Pre-specified analyses in patients with STEMI, NSTEMI and Stable angina were undertaken. Results Of 1227 PCI procedures performed over the period of observation, 690 were pre-pandemic and 537 were afterwards. Overall median heparin dose per case was 11000units versus 11500units (p = 0.137) and maximum ACTs were 291s versus 305s, respectively (p = 0.135). Pre-PCI TIMI 3 flow was lower during the pandemic than before (60% v 65%, p = 0.005) but Post-PCI flow was similar (96% versus 96%, p = 0.839). There were no statistically significant differences in heparin dose or achieved ACT among patients with STEMI, NSTEMI or Stable presentations. Conclusion In spite of the increasing evidence that COVID-19 infection causes thrombosis, it appears that standard heparin management during PCI is sufficient to achieve effective anticoagulation and avoid peri-procedural thrombotic complications. Group 1 Pre PandemicGroup 2 PandemicP valueNumber of doses given3 (3 to 4)3 (3 to 4)0.952Total Heparin dose (units)11000 (8000 to 14000)11500 (9000 to 14000)0.137Number of ACTs measured2 (1 to 2)2 (1 to 2)0.194First ACT (seconds)240 (199 to 318)248 (206 to 326)0.256Maximum ACT (seconds)291 (230 to 368)305 (239 to 369)0.135Heparin dose and Activated Clotting Times (ACT) in patients undergoing PCI before Covid-19 pandemic (Group 1) and during pandemic (Group 2); median and interquartile rangesAbstract Figure. Clinical Presentation

Conventional Weight-Based versus Low-Dose Regimen of Heparin Administration to Achieve Target Activated Clotting Time on Cardiopulmonary Bypass in Pakistani Population

Objective: A weight-based dose of heparin is calculated to achieve target ACT (Activated clotting time) for establishing CPB (cardiopulmonary bypass). Whether a target ACT can be achieved with lower dose of heparin in Pakistani population was the aim of this study. Methodology: The cross-sectional comparative study was conducted at Rawalpindi Institute of Cardiology, Department of Cardiac Surgery from 1st January 2019 to 1st January 2020. Three hundred thirty-six (336) patients undergoing elective open-heart surgeries on CPB were included in this study. Patients receiving weight-based heparin dose were placed in Group-A, while those on low-dose heparin were placed in Group-B. ACT was considered to have reached the target value in range of 400-480 seconds, values between 481-1500 seconds were considered excessive, whereas ACT of >1500 was regarded as potentially high-risk for peri-operative bleeding . Results: 14.1% (n= 28) of Group-A patients achieved target ACT, whereas 58.3% (n=116) exceeded the target of 480. In 25.1% (n=50), ACT values were beyond the measuring capacity of the assay machine i.e. >1500. Only 2.5% (n=5) required additional dosage of heparin. Target ACT in Group B was achieved in 19.7% (n= 27), 55.5% (n=76) had excessive ACT values, whereas in 16.8% (n= 23), it was >1500. 9.5% (n=13) required an additional dosage of Heparin. Conclusion: In Pakistani population, a target ACT can be achieved with significantly lower dose than the conventional weight-based heparin dose. Larger studies, preferably randomized controlled trials are needed to determine the optimal heparin dose calculation for safe anti-coagulation during CPB.