Level Of Anticoagulation Research Articles

Concomitant use of antiseizure medications is associated with lower plasma levels of direct oral anticoagulants.

Concomitant use of antiseizure medications is associated with lower plasma levels of direct oral anticoagulants.

Troubleshooting heparin resistance.

The term heparin resistance is likely best defined as the failure of an appropriate dose of unfractionated heparin (UFH) to achieve a predetermined level of anticoagulation. Unfortunately, and despite many prior reports, there is no established consensus as to what either the appropriate dose or the predetermined level should be. Traditionally, assays used to monitor anticoagulation with UFH have been clot based, including the activated partial thromboplastin time, used for patients on the ward or intensive care unit, and the activated clotting time, used for patients undergoing vascular interventions and cardiopulmonary bypass. Unfortunately, these tests may be highly influenced by other factors occurring in many patients, especially those with inflammation or acute infection, as noted during the COVID-19 pandemic. Many hospitals have thus moved to anti-Xa testing for heparin monitoring. Another important factor in defining heparin resistance includes dosing, whether weight-based or total daily dosing is used, as initial reports of heparin resistance described daily doses independent of body weight. Multiple causes of apparent heparin resistance include hypercoagulability, antithrombin deficiency, andexanet alfa used for direct oral anticoagulant reversal, thrombocytosis, and antiphospholipid antibody syndromes. Treatment options for managing patients with heparin resistance include weight-based dosing and administration of additional UFH, antithrombin supplementation, or the use of an alternative anticoagulant such as the direct thrombin inhibitors bivalirudin or argatroban.

Comparative Investigation of Thromboelastometry and Thrombin Generation for Patients Receiving Direct Oral Anticoagulants or Vitamin K Antagonists.

Background. Alterations induced by direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) to thromboelastometry and thrombin generation are not well defined. We performed a simultaneous investigation of thromboelastometry and thrombin generation for patients who were chronically anticoagulated with DOACs or VKAs. Methods. A total of 131 patients on DOACs [apixaban (n = 37), rivaroxaban (n = 34), dabigatran (n = 30), edoxaban (n = 30)] and 33 on VKAs were analyzed. Whole blood was analyzed for thromboelastometry and plasma was analyzed for thrombin generation. Results. While the thromboelastometry clotting time (CT) was responsive to the hypocoagulability induced by DOACs or VKAs, clot formation time and maximal clot formation were not. Cumulatively, the parameters denoting the velocity of thrombin generation (lag time, time-to-peak) were relatively less responsive to the hypocoagulability induced by VKAs than DOACs. Conversely, the parameters denoting the quantity of thrombin generation [peak-thrombin and the endogenous thrombin potential (ETP)] were more responsive to the hypocoagulability induced by VKAs than DOACs. Apixaban showed relatively small differences (peak vs. trough) in the plasma concentration and a relatively small (peak vs. trough) difference of hypocoagulability when assessed by the CT or the ETP. The CT and the ETP were strongly correlated with DOAC concentrations or with the VKA-INR. Conclusions. DOACs and VKAs altered thromboelastometry and thrombin generation to an extent that probably reflects the mode of action of these drugs and may also have practical implications for patients' management. Apixaban showed a small difference of hypocoagulability (peak vs. trough), suggesting a more stable anticoagulation over the daily course of treatment. Based on the correlations of the CT or the ETP vs. the DOAC concentrations, we estimated that critical values of the CT or the ETP would correspond to DOAC concentrations of 400 or 20 ng/mL. Whenever dedicated tests for DOAC concentrations are not available, the CT or the ETP can be used as surrogates to evaluate the level of anticoagulation induced by DOACs.

Vascular Complications After Venoarterial Extracorporeal Membrane Oxygenation Support: A CT Study.

Vascular complications after venoarterial extracorporeal membrane oxygenation (ECMO) remains poorly studied, although they may highly impact patient management after ECMO removal. Our aim was to assess their frequency, predictors, and management. Retrospective, observational cohort study. Two ICUs from a tertiary referral academic hospital. Adult patients who were successfully weaned from venoarterial ECMO between January 2021 and January 2022. None. Vascular complications frequency related to ECMO cannula. A total of 288 patients were implanted with venoarterial ECMO during the inclusion period. One hundred ninety-four patients were successfully weaned, and 109 underwent a CT examination to assess for vascular complications until 4 days after the weaning procedure. The median age of the cohort was 58 years (interquartile range [IQR], 46-64 yr), with a median duration of ECMO support of 7 days (IQR, 5-12 d). Vascular complications were observed in 88 patients (81%). The most frequent complication was thrombosis, either cannula-associated deep vein thrombosis (CaDVT) (n = 63, 58%) or arterial thrombosis (n = 36, 33%). Nonthrombotic arterial complications were observed in 48 patients (44%), with 35 (31%) presenting with bleeding. The most common site of CaDVT was the inferior vena cava, occurring in 33 (50%) of cases, with 20% of patients presenting with pulmonary embolism. There was no association between thrombotic complications and ECMO duration, anticoagulation level, or ECMO rotation flow. CT scans influenced management in 83% of patients. In-hospital mortality was 17% regardless of vascular complications. Vascular complications related to venoarterial ECMO cannula are common after ECMO implantation. CT allows early detection of complications after weaning and impacts patient management. Patients should be routinely screened for vascular complications by CT after decannulation.

Clinical, Laboratory, and Molecular Characteristics of Inherited Vitamin K-Dependent Coagulation Factors Deficiency.

Vitamin K-dependent coagulation factors deficiency (VKCFD) is a rare autosomal recessive genetic disease characterized by impaired levels of multiple coagulation factors (II, VII, IX, and X) and natural anticoagulants (proteins C and S). VKCFD is part of familial multiple coagulation factor deficiencies, reporting overall 50 affected families thus far. Disease manifestations are quite heterogeneous, bleeding symptoms may vary, and even, although generally mild, some patients may succumb to fatal outcomes. VKCFD diagnosis may be delayed because the disease phenotype simulates the most frequently acquired deficiencies of vitamin K. First-line coagulation assays, prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT), are both prolonged; mixing test typically normalizes the clotting times; and vitamin K-dependent coagulation factors will be variably decreased. Molecularly, VKCFD is associated with mutations in γ-glutamyl-carboxylase (GGCX) or vitamin K epoxide reductase complex subunit 1 (VKORC1) genes. Vitamin K is involved not only in the biosynthesis of coagulation proteins but also in bone metabolism and cell proliferation. Therapeutic options are based on vitamin K supplementation, coagulation factors (prothrombin complex), and fresh frozen plasma, in case of severe bleeding episodes. Two case studies here illustrate the diagnostic challenges of VKCFD: case 1 depicts a woman with a history of bleeding episodes, diagnosed, only in her third decade of life with inherited homozygous GGCX gene mutation. Case 2 shows a man with an acquired vitamin K deficiency caused by Crohn's disease. Better understanding of GGCX and VKORC1 mutations aids in prognosis and treatment planning, with emerging insights suggesting potential limitations in the effectiveness of vitamin K supplementation in certain mutations.

V-A ECMO weaning with pump-controlled retrograde trial off (PCRTO) approach: an illustration of safety, benefits and feasibility

Abstract Introduction Weaning cardiogenic shock patients off V-A ECMO is a crucial but difficult step in the management of these patients. Conventional weaning strategies reduce the ECMO flow to approximately 1 L/min, yet this still entails significant unloading of the cardiopulmonary circulation. Background The PCRTO technique enables controlled retrograde flow of oxygenated blood from the patient’s arterial side into the right ventricle, resulting in an incremental increase of 0.5 L/min in right ventricular preload. This process challenges and evaluates the entire cardiopulmonary system (Figure). Methods We prospectively examined the use of the Pump-Controlled Retrograde Trial Off (PCRTO) approach (-0.5 L/min) compared to conventional ECMO weaning (+1 L/min) in a cross over study including 14 V-A ECMO patients across three quaternary high-output cardiogenic shock centers. Both the conventional and the PCRTO-technique are performed under continuous cardiac echo and PA-catheter guidance. Results After achieving adequate anticoagulation levels (Xa>0.3), no thrombotic or other complications were observed, confirming 100% safety of this technique. Table 1 provides an overview of our PCRTO-cohort and their evaluation after conventional versus PCRTO weaning. In 43% (6/14) of our cohort, conventional weaning strategies determined feasibility of ECMO-device weaning, while ultimately failing with PCRTO due to e.g. right ventricular failure or oxygenation failure. In contrast, 4/14 patients who failed the conventional weaning showed a positive weaning potential with PCRTO, potentially enabling patients to be liberated from bridging to durable ventricular assist devices or heart transplant. Conclusions In conclusion, PCRTO is a safe weaning strategy that increases the likelihood of successful weaning in critically ill V-A ECMO patients by challenging oxygenation/ventilation and cardiac circulation through increased right ventricular preload and reduced left ventricular afterload. Here, PCRTO ultimately led to a different destination scenario in 78,5% of our patient cohort compared to conventional V-A ECMO weaning alone. PCRTO may provide a standardised, reproducible approach to ECMO assessment and liberation which will be useful for future clinical trials in this population.

IRON OVER LOAD AND ITS RELATION WITH HAEMOSTATIC PARAMETERS IN BETA-THALASSEMIA PATIENTS

Background: Patients with beta-thalassemia major have been observed to experience changes in their coagulation profile. These changes include an elongated prothrombin time and partial thromboplastin time as well as bring down levels of natural anticoagulants and coagulation factors. The mechanisms underlying the occurrence of thrombotic tendencies in some thalassemia patients remain unclear. This study aims to examine the alterations in the iron and coagulation profile among beta-thalassemia patients. Methods: After informed consent, 50 children having beta-thalassemia, and 50 healthy controls were included in this study. Blood samples were collected and serum ferritin, haematological and haemostatic parameters were measured. Data was analysed on SPSS-24. Results: The laboratory assessment revealed 43.5% of the patients had thrombocytopenia, 54% had prolonged prothrombin time (PT), and 56% of the patients had prolonged activated partial thromboplastin time (aPTT). All estimated coagulation factors exhibited lower activity levels in comparison to the control group. Serum ferritin exhibited a positive relationship with PT and aPTT and a substantial negative relationship with total platelet count. Conclusion: High serum ferritin levels are associated to abnormal haemostatic parameters in thalassemia patients. Regular monitoring of serum ferritin levels is essential to ensure that thalassemia patients receive appropriate treatment and support. Pak J Physiol 2024;20(3):71–3, DOI: https://doi.org/10.69656/pjp.v20i3.1742

Evaluating chemical venous thromboembolism prophylaxis in trauma patients at a single Australian center.

Trauma patients are at an elevated risk of developing venous thromboembolism (VTE), with the subsequent mortality in patients requiring intensive care unit admission ranging from 25% to 38%. There remains significant variability in clinical practice related to VTE prophylaxis in trauma patients due to the frequent presence of contraindications impacting the timing and consistency of application. This study aimed to assess the effectiveness of the current practice of chemical VTE prophylaxis in trauma patients at a single Australian center. A prospective review was conducted on patients admitted to the ACT Trauma Service (Canberra, Australia) from July to November 2022. The included patients were 18 years or older, without a direct contraindication to anticoagulation, who received chemical VTE prophylaxis with low-molecular-weight heparin (enoxaparin) for at least three doses and underwent subsequent testing of anti-factor Xa (aFXa) levels. During the study period, 187 patients were admitted, of whom 63 were included in the study. Of these, 47 patients achieved therapeutic levels of anticoagulation as determined by their aFXa levels, while 16 were subtherapeutic. The only statistically significant difference between the two groups was in weight, with patients in the subtherapeutic group weighing an average of 91.9 kg compared to 79.1 kg in the therapeutic group (P<0.05). A fixed-dose enoxaparin regimen was utilized, with limited individualization based on patient factors, such as injuries, comorbidities, and other biological factors. Sixteen patients (25%) had subtherapeutic VTE prophylaxis, as measured by aFXa levels. Higher weight was significantly correlated with inadequate VTE prophylaxis dosing. While age, sex, and smoking status might play important roles in clinical decision-making, weight-based dosing of low-molecular-weight heparin may be more effective in achieving adequate VTE prophylaxis.

Vkorc1 polymorphisms of the Norway rats in China: Implications for rodent management and evolutionary origin of anticoagulant resistance mutations

The extensive utilization of second-generation anticoagulant rodenticides (SGARs) has raised concerns regarding non-target animal safety and environmental contamination. It is essential to assess the anticoagulant resistance level in rodent populations and prioritize the use of relative low toxic first-generation anticoagulant rodenticides (FGARs) in susceptible rodent populations. Mutations in the vitamin K epoxide reductase complex subunit 1 (Vkorc1) gene confer anticoagulant resistance in Norway rats. However, the Vkorc1 polymorphisms remain unclear in most Norway rat populations in China although anticoagulant rodenticides have been widely used in China since the 1980s. Analysis of the Vkorc1 polymorphisms in 489 rats across China, combined with in silico binding affinity analysis, revealed three potential resistance mutations A26T, C96Y, and A140T at three distinct locations. In the remaining locations, Vkorc1 resistance mutations were absent, indicating that the FGARs could be effective in these areas. Additional evolutionary analysis of different Vkorc1 mutations suggested that the three missense mutations identified in China might have evolved independently as de novo mutations, and the resistance mutations in Europe are unlikely to be pre-existing variations in China. Further analysis of Vkorc1 haplotypes among European resistant rat populations is essential for understanding the origin of these resistance mutations. These findings emphasize the importance of customizing rodent control strategies in China based on regional resistance levels and gaining insights into the origins of Vkorc1 mutations for more effective rodent management strategies.

Systematic review of clinical guidelines and consensus statements concerning heparin and protamine dosing and monitoring of anticoagulation levels for non-cardiac arterial procedures.

This systematic review was performed to examine all published practice Guidelines and Consensus Statements (together: GCS) on heparin dosing and monitoring during non-cardiac arterial procedures (NCAP). The objective was to scrutinize the recommendations and advice outlined within these GCS documents and to evaluate the supporting evidence for these recommendations. Additionally, the use of the activated clotting time (ACT) and target ACT values were explored. This systematic review was performed in accordance with the PRISMA Guidelines. Medline and Embase databases were searched to identify all GCSs in the English language on NCAP. The final literature search was performed in January 2023. This search was supplemented by searching websites of relevant professional vascular surgical organizations for GCSs. Titles and abstracts were assessed by two independent reviewers. Of 9716 titles identified, 27 GCSs met the predefined inclusion criteria: six GCSs regarding carotid intervention, seven regarding procedures for aneurysmal disease of the abdominal aorta and iliac arteries, 12 regarding interventions for acute and chronic peripheral arterial occlusive disease and two regarding open and endovascular interventions of thoraco-abdominal aortic aneurysms. Administration of heparin is advised for al NCAP. There was high variability concerning heparin dose: both standard dose as weight based dosing (30-150 IU/kg) was advised. Recommendations on repeated doses, ACT monitoring and heparin reversal using protamine also varied widely. In none of the GCSs, the type of the ACT measuring device or used cartridges were specified. Large variability was found between the included GCSs with regard to the recommendations on heparin dose and target ACT values during NCAP. Advice and recommendations in GCSs were based on low-quality studies or without providing any reference at all. The described variability in recommendations emphasizes the need for large prospective (randomized) studies or the incorporation of data on heparin and the use of ACT monitoring into verified vascular surgery registries, to develop evidence-based, practical and uniform applicable recommendations.

Heparin-Calibrated Anti-Factor Xa Assay for the Measurement of Direct Anticoagulants such as Apixaban, Rivaroxaban, and Edoxaban.

The first purpose of this study was to determine whether a measurement of the level of direct oral anticoagulants (DOACs) was possible with heparin-calibrated chromogenic anti-factor Xa activity (AXA). The second purpose of this study was to evaluate whether the antidote treatment decision level (30 or 50 ng/mL of DOAC) can be determined by unfractionated heparin (UHF)/low molecular weight heparin (LMWH)-calibrated AXA. AXA was measured by using two reagents and dedicated analyzers (Sysmex CS-5100 analyzer and STA R Max3). Four types of calibrators were used: 1) Stago DOAC (rivaroxaban, edoxaban, and apixaban)-specific calibrator, 2) Stago LMWH calibrator, 3) Sysmex UHF calibrator, and 4) Sysmex LMWH calibrator. Regression analysis was used between assays. Receiver operating characteristic (ROC) curves were performed, and the concordance rate was calculated. The correlation coefficients were in the range of 0.75 - 0.91 for rivaroxaban and 0.81 - 0.94 for apixaban. The correlation coefficient between edoxaban-calibrated AXA and Sysmex LMWH/Sysmex UHF calibrator-calibrated AXA was low (r = 0.47). Overall correlation between DOAC-calibrated AXA and Stago LMWH-calibrated AXA was linear, at only low concentration in all three DOACs. The concordance rate (89.3 - 100%) is good for de-termining the antidote management level by UFH/LMWH-calibrated AXA, compared with those of DOAC-calibrated AXA in rivaroxaban and apixaban. The concordance rate ranged from 63% to 67% between Sysmex UFH/ LMWH-calibrated AXA and edoxaban-calibrated AXA. The findings of our study suggest limitations in calculating accurate concentrations, when using UFH/LMWH-calibrated AXA to measure DOAC. This study demonstrates that UFH/LMWH-calibrated AXA may be useful in determining the presence of DOACs at the cutoff level for the antidote treatment in rivarovaban and apixaban. However, in edoxaban, UFH/LMWH-calibrated AXA could not accurately measure the presence of DOACs at the cutoff for antidote treatment.

90: The role of Viscoelastic Coagulation Monitor™ (VCM) heparinase test to monitor anticoagulation level and to predict platelet transfusion threshold under heparin administration in veno-venous ECMO patients

90: The role of Viscoelastic Coagulation Monitor™ (VCM) heparinase test to monitor anticoagulation level and to predict platelet transfusion threshold under heparin administration in veno-venous ECMO patients

The use of reduced DOAC doses in atrial fibrillation patients does not always lead to good anticoagulation levels and avoid adverse events

BackgroundThe MAS study (Blood Advances 2024) showed that a high proportion of Italian AF patients treated with direct oral anticoagulants (DOACs) receive reduced doses. This sub-analysis of MAS data aimed to analyze the effects of reduced (appropriate or not)- or standard-dose use on DOAC activity assessed at baseline and the occurrence of thrombotic or bleeding complications during follow-up. MethodsThe MAS study design, the methods for DOAC measurement, the results, and the adverse events during follow-up, are described in detail elsewhere. ResultsSeven hundred AF patients (42 % of the total 1657) received a reduced dose (considered inappropriate in 140 [20 %]). They were older, more frequently women, with lower body mass index (BMI), hemoglobin levels, and creatinine clearance. They more often had cerebral or cardiovascular diseases, were taking more medications, with higher scores for thrombotic or bleeding risk. Despite the use of low doses, 133 (19.0 %) patients had high standardized C-trough DOAC levels and experienced a high proportion of bleeding events (8.3 % per year). Conversely, some patients (4.7 %) had very low levels, resulting in a high incidence of thrombotic events (6.7 % per year). No difference was detected if the reduced dose was appropriate or not. ConclusionThe unpredictable, highly variable inter-individual anticoagulant effect of DOACs may lead to either too low or too high anticoagulant levels, increasing the risk of thrombotic or bleeding events. This is particularly relevant for patients with high-risk conditions, such as those chosen for reduced-dose treatment. Further studies are needed to investigate this important clinical issue.

Chemokine receptor ACKR3/CXCR7 influences interactions with lipoproteins and anticoagulant acylcarnitine levels: Implications for atherothrombotic disposition in coronary artery disease

Chemokine receptor ACKR3/CXCR7 influences interactions with lipoproteins and anticoagulant acylcarnitine levels: Implications for atherothrombotic disposition in coronary artery disease

Impact of Direct Oral Anticoagulant Levels on Functional Independence Following Endovascular Thrombectomy in Patients With Atrial Fibrillation

Background In direct oral anticoagulant (DOAC) users with stroke due to large artery occlusion, endovascular thrombectomy is an effective treatment when intravenous thrombolytic therapy is unsuitable. The purpose of this study is to investigate the association between emergent DOAC levels and endovascular thrombectomy outcomes. Methods Participants with atrial fibrillation, who had a premorbid modified Rankin Scale score of ≤3 and had undergone endovascular thrombectomy for acute stroke, were enrolled. Drug levels upon hospital arrival were measured in the prestroke DOAC users. Head noncontrast computed tomography and computed tomographic angiography images were used to quantify thrombus permeability. The primary outcome was functional independence at 3 months (modified Rankin Scale 0–2 or a return to premorbid status for patients with a premorbid modified Rankin Scale of 3). Results The study included 250 patients (antithrombotic agent nonusers, 42.0%; oral anticoagulant users, 34.0%; and antiplatelet users, 24.0%). The primary outcomes did not differ among the 3 groups. Among oral anticoagulant users, 78.8% were DOAC users. Of the 59 DOAC users with available drug level measurements, 62.7% had low levels (&lt;50 ng/mL). Low‐level patients were less likely to achieve functional independence than high‐level patients (adjusted odds ratio, 0.26 [0.08–0.87]). Compared with antithrombotic nonusers, oral anticoagulant users with therapeutic anticoagulation were more likely to achieve functional independence (adjusted odds ratio, 2.83 [1.18–6.78]), whereas those with inadequate anticoagulation did not. Symptomatic intracerebral hemorrhage occurred in 3 DOAC users in the low‐level group (8.1%), 1 DOAC user in the high‐level group (4.5%), and 4 antithrombotic nonusers (3.8%). Thrombus permeability was similar between antithrombotic nonusers and low‐ or high‐level DOAC users. Conclusion Among patients who underwent DOAC therapy and endovascular thrombectomy, those with low DOAC levels were less likely to achieve functional independence. Furthermore, oral anticoagulant users with therapeutic anticoagulation displayed better functional outcomes than antithrombotic nonusers.

More early bleeds associated with high baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study

AbstractTreatment with direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is effective and safe. However, bleeding complications still occur. Whether DOAC level measurement may further improve treatment efficacy and safety is still an open issue. In the "Measure and See" study, venous blood was collected 15-30 days after DOAC initiation in patients with AF who were then followed up for 1 year to record the occurrence of major and clinically relevant nonmajor bleeding. DOAC plasma levels were measured in 1 laboratory, and results were kept blind to patients and treating doctors. Trough DOAC levels were assessed in 1657 patients (957 [57.7%] and 700 patients treated with standard and low-dose, respectively). Fifty bleeding events were recorded during 1606 years of follow-up (3.11% pt/yrs). Fifteen bleeding events (4.97% pt/yrs) occurred in patients with C-trough standardized values in the highest activity class (>0.50), whereas 35 events (2.69% pt/yrs) occurred in those with values in the 2 lower classes (≤0.50, P = .0401). Increasing DOAC levels and low-dose DOAC use were associated with increased bleeding risk in the first 3 months of treatment. Overall, 19% of patients receiving low doses had standardized values in the highest class. More bleeding occurred in patients on low (4.3% pt/yrs) vs standard (2.2% pt/yrs; P = .0160) dose DOAC. Early measurement of DOAC levels in patients with AF identified many individuals with high levels despite the low doses use and had more bleeding risk during the first 3 months of treatment. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.

Anticoagulant Therapy in Pregnant Women with Mechanical Heart Valves: Italian Federation of Centers for Diagnosis and Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

The management of anticoagulant therapy in pregnant women with mechanical heart valves (MHVs) is difficult and often challenging even for clinicians experienced in the field. These pregnancies, indeed, are burdened with higher rates of complications for both the mother and the fetus, compared to those in women without MHVs. The maternal need for an optimal anticoagulation as provided by vitamin K antagonists is counterbalanced by their teratogen effect on the embryo and fetus. On the other hand, several concerns have been raised about the efficacy of heparins in pregnant women with MHVs, considering the high risk of thrombotic complications in these patients. Therefore, numerous clinical issues about the management of pregnant women with MHVs remain unanswered, such as the selection of the best anticoagulant agent, the optimal anticoagulation levels to be achieved and maintained, and the evaluation of long-term effects for both the mother and the fetus. Based on a comprehensive review of the current literature, the Italian Federation of the Centers for the Diagnosis and the Surveillance of the Antithrombotic Therapies (FCSA) proposes experience-based suggestions and expert opinions. Particularly, this consensus document aims at providing practical guidance for clinicians dealing with pregnant women with MHVs, to optimize maternal and fetal outcomes while guaranteeing adequate anticoagulation. Finally, FCSA highlights the need for the creation of multidisciplinary teams experienced in the management of pregnant women with MHVs during pregnancy, delivery, and postpartum, in order to better deal with such complex clinical issues and provide a comprehensive counseling to these patients.

Activated clotting time-guided heparinization during open AAA surgery: a pilot study

BackgroundArterial thrombo-embolic complications (TEC) are still common during and after non-cardiac arterial procedures (NCAP). While unfractionated heparin has been used during NCAP for more than 70 years to prevent TEC, there is no consensus regarding the optimal dosing strategy. The aim of this pilot study was to test the effectiveness and feasibility of an activated clotting time (ACT)-guided heparinization protocol during open abdominal aortic aneurysm (AAA) surgery, in anticipation of a randomized controlled trial (RCT) investigating if ACT-guided heparinization leads to better clinical outcomes compared to a single bolus of 5000 IU of heparin.MethodsA prospective multicentre pilot study was performed. All patients undergoing elective open repair for an AAA (distal of the superior mesenteric artery) between March 2017 and January 2020 were included. Two heparin dosage protocols were compared: ACT-guided heparinization with an initial dose of 100 IU/kg versus a bolus of 5000 IU. The primary outcome was the effectiveness and feasibility of an ACT-guided heparinization protocol with an initial heparin dose of 100 IU/kg during open AAA surgery. Bleeding complications, TEC, and mortality were investigated for safety purposes.ResultsA total of 50 patients were included in the current study. Eighteen patients received a single dose of 5000 IU of heparin and 32 patients received 100 IU/kg of heparin with additional doses based on the ACT. All patients who received the 100 IU/kg dosing protocol reached the target ACT of > 200 s. In the 5000 IU group, TEC occurred in three patients (17%), versus three patients (9.4%) in the 100 IU/kg group. Bleeding complications were found in six patients (33%) in the 5000 IU group and in 9 patients (28%) in the 100 IU/kg group. No mortality occurred in either group.ConclusionsThis pilot study demonstrated that ACT-guided heparinization with an initial dose of 100 IU/kg appears to be feasible and leads to adequate anticoagulation levels. Further randomized studies seem feasible and warranted to determine whether ACT-guided heparinization results in better outcomes after open AAA repair.

Semisynthesis of new sulfated heterorhamnan derivatives obtained from green seaweed Gayralia brasiliensis and evaluation of their anticoagulant activity

Marine green algae produce sulfated polysaccharides with diverse structures and a wide range of biological activities. This study aimed to enhance the biotechnological potential of sulfated heterorhamnan (Gb1) from Gayralia brasiliensis by chemically modifying it for improved or new biological functions. Using controlled Smith Degradation (GBS) and O-alkylation with 3-chloropropylamine, we synthesized partially water-soluble amine derivatives. GBS modification increase sulfate groups (29.3 to 37.5 %) and α-l-rhamnose units (69.9 to 81.2 mol%), reducing xylose and glucose, compared to Gb1. The backbone featured predominantly 3- and 2-linked α-l-rhamnosyl and 2,3- linked α-l-rhamnosyl units as branching points. Infrared and NMR analyses confirmed the substitution of hydroxyl groups with aminoalkyl groups. The modified compounds, GBS-AHCs and GBS-AHK, exhibited altered anticoagulant properties. GBS-AHCs showed reduced effectiveness in the APTT assay, while GBS-AHK maintained a similar anticoagulant activity level to Gb1 and GBS. Increased nitrogen content and N-alkylation in GBS-AHCs compared to GBS-AHK may explain their structural differences. The chemical modification proposed did not enhance its anticoagulant activity, possibly due to the introduction of amino groups and a positive charge to the polymer. This characteristic presents new opportunities for investigating the potential of these polysaccharides in various biological applications, such as antimicrobial and antitumoral activities.

Natural Anticoagulant Protein Levels in Patients With Beta-Thalassemia Major: A Case-Control Study.

β-thalassemia is a group of inherited blood disorders that affect the production of β-globin chains, leading to the reduction or absence of these chains. One of the complications observed in patients with β-thalassemia major (β-TM) is thrombosis, especially in those who receive frequent blood transfusions. This may be due to a decrease in the levels of the natural anticoagulants: protein C (PC), total protein S (PS), and antithrombin (AT). In this case-control study, patients with β-TM, who had received at least 20 packed cell transfusions during their lifetime, were included. Patients with other underlying diseases like bleeding or thrombotic disorders were excluded. Totally, 118 patients with β-TM and 120 healthy individuals were included. The mean level of PC and AT was significantly lower in patients with β-TM (48.2 ± 65.4 and 57.42 ± 13.6, respectively) compared to the control group (97.1 ± 21.46 and 81.79 ± 14.3, respectively), with P value of 0.001 and 0.01, respectively. Although the difference was not statistically significant (P = 0.1), a similar trend was observed for total PS (61.12 ± 21.12 for patients versus 72.2 ± 35.2 for the control group). Of note, the decrease in PC, AT, and total PS levels compared to the control group was 50.36%, 27.5%, and 15.34%, respectively. It seems that β-TM patients who receive prolonged blood transfusions frequently are at an increased risk of decreased in natural anticoagulants levels and therefore potentially are at risk of thrombosis.