BACKGROUND: The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors.
METHODS: This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method.
RESULTS: Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0-11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0-5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban.
CONCLUSIONS: Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.

Activated clotting times (ACTs) are used to screen for coagulopathies and monitor heparin therapy.
To determine a reference interval (RI) for ACT in dogs using a point-of-care analyser, to quantify intra-subject within- and between-day variability, to quantify analyser reliability and inter-analyser agreement and to study the influence of a delay in measurement.
Forty-two healthy dogs were included. Measurements were performed on fresh venous blood using the i-STAT 1 analyser. The RI was determined using the Robust method. Intra-subject within-day variability and between-day variability were quantified between baseline and 2 h (n = 8) or 48 h (n = 10) later. Analyser reliability and inter-analyser agreement were studied by duplicate measurements (n = 8) on identical analysers. The influence of measurement delay was studied before and after a delay of one analytical run (n = 6).
Mean, lower and upper reference limits for ACT were 92.9 ± 9.1, 74.4 and 111.2 s, respectively. Coefficients of variation of intra-subject within- and between-day variability were 8.1% and 10.4%, respectively, resulting in a significant between-day measurement difference. Analyser reliability assessed by the intraclass correlation coefficient and coefficient of variation were 0.87% and 3.3%, respectively. Significantly lower ACT values were observed after a measurement delay compared to direct analysis.
Our study provides an RI for ACT in healthy dogs using the i-STAT 1 and suggests low intra-subject within- and between-day variability. Analyser reliability and inter-analyser agreement were good; however, analysis delay and between-day differences could significantly influence ACT results.

Heparin is a common anticoagulant, but heparin overdose is a common intensive care unit (ICU) medication error due to the narrow therapeutic window of heparin. Conventional methods to monitoring heparin suffer from long turnaround time, the need for skilled personnel, and low frequency of sampling. To overcome these issues, we describe here a fiber optic photoacoustic (PA) sensor for real-time heparin monitoring. The proposed sensor was validated with in vitro testing and in a simulated in vivo model using the following samples: (1) phosphate-buffered saline (PBS), (2) spiked human plasma, (3) spiked whole human blood, and (4) clinical samples from patients treated with heparin. Samples were validated by comparing the PA signal to the activated partial thromboplastin time (aPTT) as well as the activated clotting time (ACT). Importantly, the proposed sensor has a short turnaround time (3 min) and a limit of detection of 0.18 U/ml in whole human blood. The PA signal is linear with heparin dose and correlates with the aPTT value (Pearson\'s r = 0.99). The PA signal from 32 clinical samples collected from eight patients linearly correlated with ACT values (Pearson\'s r = 0.89, in vitro; Pearson\'s r = 0.93, simulated in vivo). The PA signal was also validated against the cumulative heparin dose (Pearson\'s r = 0.94, in vitro; Pearson\'s r = 0.96, simulated in vivo). This approach could have applications in both in vitro and real-time in vivo heparin monitoring.

Anticoagulation monitoring during transition from direct oral anticoagulants (DOAC) to heparin infusions is a significant challenge. Factor Xa inhibitors influence the heparin calibrated antifactor Xa assay. The University of Virginia (UVA) Medical Center utilized a corrected antifactor Xa assay (c-AXA) during this transition period, which removes DOAC-mediated antifactor Xa activity (d-AXA) and reflects heparin-specific activity. Currently, the duration of this influence is not well described.
This study had two aims: to determine if the initial d-AXA is predictive of the duration of DOAC influence and to further characterize this influence among different patient populations.
This retrospective study included adult patients admitted to UVA Medical Center between September 2016 and March 2017, with c-AXA measurements, who received apixaban or rivaroxaban within 48 hours before heparin initiation. A Pearson correlation test, Kaplan-Meier Survival Analysis, and multivariate linear regression were used to assess the relationship between initial d-AXA and duration of influence.
Sixty-eight patients met inclusion criteria and were maintained on either apixaban (85%) or rivaroxaban (15%) before heparin initiation. The initial d-AXA ranged from 0.11 to 3.27 IU/ml. The mean duration of influence was 69.3 ± 46.2 hours, with a median duration of 62.7 hours. No strong correlation was identified between initial d-AXA and duration of influence (R2 = 0.124). Presence of interacting medications significantly increased duration of influence (p=0.012). No significant difference in duration of influence existed between patients with normal renal function and those with dynamic renal function (p=0.84), or with body mass index (BMI) greater than 40 kg/m2 (p=0.16).
The initial d-AXA was not predictive of duration of influence in patients transitioning from DOACs to heparin infusion; however, the median duration of influence suggests influence may be present for longer than currently stated in the literature, especially in those taking interacting medications.

UNASSIGNED: Intravenous unfractionated heparin infusion is often used to minimize the duration of time without anticoagulation around delivery in pregnant patients with high thrombotic risk. Activated partial thromboplastin time is commonly used to monitor and adjust heparin dose. However, using activated partial thromboplastin time is problematic in pregnancy because activated partial thromboplastin time response to unfractionated heparin is attenuated due to elevated Factor VIII levels and may lead to incorrect dosing.
UNASSIGNED: We report a case of deep venous thrombosis occurring in a term pregnancy managed by intravenous unfractionated heparin adjusted using anti-Xa level around the time of delivery. We modified the intravenous unfractionated heparin nomogram by using anti-Xa levels instead of activated partial thromboplastin time and observed lower dosing of unfractionated heparin than otherwise required to achieve and maintain target levels.
UNASSIGNED: This report demonstrates the feasibility and effectiveness of using anti-Xa level to monitor and adjust intravenous unfractionated heparin infusion in pregnancy.

OBJECTIVE: This case series presents 3 patients with acute kidney injury taking apixaban or rivaroxaban and transitioning to a heparin infusion.
CONCLUSIONS: Case 1 was a 78-year-old man admitted with respiratory failure, acute decompensated heart failure, and acute kidney injury. He was taking apixaban for atrial flutter. He was transitioned to an i.v. heparin infusion and had 2 consecutive heparin antifactor-Xa levels greater than 2 units/mL. Heparin was held and resumed about 36 hours later when the apixaban anti-Xa level was less than 50 ng/mL. Case 2 was a 55-year-old man admitted with acute kidney injury, taking apixaban for a recent deep vein thrombosis. Apixaban anti-Xa levels were monitored and i.v. heparin was initiated when the level was less than 100 ng/mL, about 56 hours after the last apixaban dose. Case 3 was a 64-year-old woman admitted with sepsis and acute kidney injury taking rivaroxaban for pulmonary embolism, which occurred 2 weeks prior to admission. Rivaroxaban anti-Xa levels were monitored and i.v. heparin was initiated about 36 hours after the last dose when the level was less than 100 ng/mL. The management strategy did not lead to any thrombotic outcomes; however, 1 patient experienced bleeding.
CONCLUSIONS: Specific anti-Xa levels for rivaroxaban and apixaban appeared to be helpful in the transition of 3 patients to unfractionated heparin infusions in the setting of acute kidney injury. These levels provided enhanced, individualized care and likely helped avoid over and under anticoagulation.

For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure, and there are increasingly numbers of centers worldwide performing ECLS for numerous indications. Despite the progress with advancing the technology, hemorrhagic and thrombotic complications are frequently reported and associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and an artificial circuit, anticoagulation is necessary and there is resultant activation of coagulation, fibrinolysis, as well as, an increased inflammatory response. While unfractionated heparin (UFH) remains the mainstay anticoagulant used during ECLS, there is a paucity of published data to develop a universal anticoagulation guideline and centers are forced to create individualized protocols to guide anticoagulation management while lacking expertise. From an international survey, centers often use a combination of tests, which in turn result in discordant results and confused management. Studies are urgently needed to investigate optimization of current anticoagulation strategies with UFH, as well as, use of alternative anticoagulants and non-thrombogenic biomaterials. Blood transfusion during extracorporeal support typically occurs for several reasons, which includes circuit priming, restoration of oxygen carrying capacity, maintenance of a hemostatic balance, and treatment of hemorrhagic complications. As a result, the majority of patients will have been exposed to at least one blood product during extracorporeal support and transfusion utilization is high. ECLS Centers have adopted transfusion thresholds based upon practice rather than evidence as there have been no prospective studies investigating the efficacy of red cell (RBC) transfusion in patients receiving extracorporeal support. In addition, RBC transfusion has been associated with increased mortality in ECLS in several retrospective studies. Additional studies are needed to establish evidence based thresholds for transfusion support and diagnostics to guide transfusion therapy to assess efficacy of transfusion in this population, as well as, exploration of alternatives to transfusion.