Antithrombin supplementation attenuates heparin resistance in plasma spiked with Gla-domainless factor Xa S195A in vitro.

BACKGROUND: Andexanet alfa is a Gla-domainless mutant (S195A) factor Xa (GDXa) approved for acute reversal of oral factor Xa inhibitors. Cardiac surgery patients exposed to andexanet before cardiopulmonary bypass often exhibit severe heparin resistance. There is a paucity of data on the effectiveness and optimal dosage of antithrombin use in this setting. The objective of this study was to evaluate the in vitro effect of increased heparin with antithrombin levels on attenuating heparin resistance induced by GDXa. METHODS: Heparinised normal pooled plasma and cardiopulmonary bypass plasma were spiked with GDXa 4 µM. Tissue factor-activated thrombin generation was used to assess heparin reversal effects of GDXa and restoration of anticoagulation with additional heparin with and without antithrombin. Serum thrombin-antithrombin complex, antithrombin activity, and tissue factor pathway inhibitor were also measured in tissue factor-activated, recalcified cardiopulmonary bypass plasma spiked with GDXa. RESULTS: In normal pooled plasma, GDXa-induced heparin reversal was mitigated by maintaining a high heparin concentration (12 U ml-1) and supplementing antithrombin (1.5-4.5 µM) based on peak and velocity of thrombin generation. Heparin reversal by GDXa was also demonstrated in cardiopulmonary bypass plasma, but supplementing both heparin (8 U ml-1) and antithrombin (3 µM) attenuated GDXa-induced changes in peak and velocity of thrombin generation by 72.5% and 72.2%, respectively. High heparin and antithrombin levels attenuated thrombin-antithrombin complex formation in tissue factor-activated, GDXa-spiked cardiopulmonary bypass plasma by 85.7%, but tissue factor pathway inhibitor remained depleted compared with control cardiopulmonary bypass plasma. CONCLUSIONS: Simultaneous supplementation of heparin and antithrombin mitigate GDXa-induced heparin resistance by compensating for the loss of tissue factor pathway inhibitor.

Trends and predictions of perioperative transfusion and venous thromboembolism in hepatectomy using a North American Registry.

BACKGROUND: Studies indicate a link between allogeneic blood transfusion and venous thromboembolism (VTE) post-major surgery. Analyzing trends and predictors of these outcomes after hepatectomy can inform risk management. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used for a retrospective analysis. Primary outcomes were perioperative red blood cell (RBC) transfusion and VTE events within 30 days of hepatectomy. Seven-year trends and predictors were evaluated. RESULTS: Among 29,131 hepatectomy patients, transfusion rates showed no statistically significant decreasing trends (p = .122) from 2014 to 2020 (18.13%-16.71%), while VTE rates showed a downward trend over the 7 years (p = .021); 17.2% received RBC transfusion, with higher rates in surgeries lasting ≥282 min (median: 220 min). Calculated RBC mass [hematocrit (%) × body weight (kg) × 10-5 × 70/ √ (body mass index/22)] at or below 1.5 L substantially increased transfusion odds. VTE was reported postoperatively in 2.6% of cases more frequently in longer cases involving transfusions. The adjusted odds ratio (aOR) of VTE escalated from the shortest operative time to the longest (3.17; 95% confidence interval [CI], 2.37-4.22). The adjusted odds of VTE doubled for transfused patients compared to non-transfused patients (aOR, 2.19; 95% CI, 1.86-2.57). CONCLUSIONS: Rates of RBC transfusion and VTE rates hepatectomy have minimally changed in the recent years. VTE prevention is challenging in extended surgeries at increased risk of bleeding and RBC transfusions. Patient-level data on coagulation and thromboprophylaxis can potentially refine risk assessment for postoperative VTE.

Relationships Between Body Mass Index, Allogeneic Transfusion, and Surgical Site Infection After Knee and Hip Arthroplasty Surgery.

BACKGROUND: Increased body mass index (BMI) is considered as an important factor that affects the need for total knee and hip arthroplasty (TKA/THA) and the rate of perioperative complications. Previous investigations have not fully established the relationship of BMI and perioperative transfusion with surgical site infection (SSI) or the relationship of BMI and perioperative transfusion after TKA or THA. METHODS: The National Surgical Quality Improvement Program database was used to perform a retrospective cohort study involving 333,223 TKA and 41,157 THA cases between 2011 and 2018. Multivariable regression assessed the associations of BMI (5 standard categories) and transfusion with SSI. Odds ratio (OR) of SSI was calculated relative to a normal BMI (18.5-24.9 kg/m 2 ) after adjustment of potential confounding factors. RESULTS: Perioperative transfusion decreased significantly over time for both TKA and THA; however, SSI rates remained steady at just under 1% for TKA and 3% for THA. In TKA, a higher OR for SSI was associated only with a BMI of 40+ (OR, 1.86; 95% confidence interval [CI], 1.60-2.18) compared to a referent BMI. In THA, increased ORs of SSI were seen for all BMI levels above normal and were highest for a BMI 40+ (OR, 3.08; 95% CI, 2.47-3.83). In TKA, ORs of transfusion decreased with increasing BMI and were lowest for a BMI 40+ (OR, 0.51; 95% CI, 0.47-0.54). In THA, ORs of transfusion began to increase slightly in overweight patients, reaching an OR of 1.36 (95% CI, 1.21-1.54) for a BMI 40+. CONCLUSIONS: SSI incidence remained unchanged despite continuous reductions in blood transfusion in TKA and THA patients over 8 years. In TKA, ORs for SSI increased, but ORs for transfusion decreased with increasing BMI above normal. Conversely, in THA, ORs for SSI and transfusion both increased for a BMI 40+, but only OR for transfusion increased in underweight patients. These findings suggest the importance of controlling obesity in reducing SSI following TKA and THA.

Coagulation management during liver transplantation: monitoring and decision making for hemostatic interventions.

PURPOSE OF REVIEW: Rebalanced hemostasis describes the precarious balance of procoagulant and antithrombotic proteins in patients with severe liver failure. This review is aimed to discuss currently available coagulation monitoring tests and pertinent decision-making process for plasma coagulation factor replacements during liver transplantation (LT). RECENT FINDINGS: Contemporary viscoelastic coagulation monitoring systems have demonstrated advantages over conventional coagulation tests in assessing the patient's coagulation status and tailoring hemostatic interventions. There is increasing interest in the use of prothrombin complex and fibrinogen concentrates, but it remains to be proven if purified factor concentrates are more efficacious and safer than allogeneic hemostatic components. Furthermore, the decision to use antifibrinolytic therapy necessitates careful considerations given the risks of venous thromboembolism in severe liver failure. SUMMARY: Perioperative hemostatic management and thromboprophylaxis for LT patients is likely to be more precise and patient-specific through a better understanding and monitoring of rebalanced coagulation. Further research is needed to refine the application of these tools and develop more standardized protocols for coagulation management in LT.

Right heart thrombus in transit: Raising bar in the management of cardiac arrest.

Right heart thrombus represents medical emergency as it is associated with acute pulmonary embolism. Right heart thrombus can manifest acutely in a dramatic fashion as cardiac arrest. Bedside echocardiography is a key to rapid diagnosis and allow early intervention. We report a case of elderly female who was admitted to our hospital after a mechanical fall and found to have hip fracture. Despite an initial uncomplicated course, she experienced cardiopulmonary arrest with right heart clot in transit identified on transesophageal echocardiography (TEE). We highlight the utility of point-of-care ultrasound as well as use of TEE to establish cause of cardiopulmonary arrest.

Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding.

Four-factor prothrombin complex concentrate (4F-PCC) is the term used to describe a pathogen-reduced, lyophilized concentrate that contains therapeutic amounts of at least 4 coagulation factors: Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX). 4F-PCC has proven to be an effective hemostatic agent compared to plasma transfusion in several prospective randomized trials in acute warfarin reversal. In recent years, 4F-PCC has been used in various acquired coagulopathies including post-cardiopulmonary bypass bleeding, trauma-induced coagulopathy, coagulopathy in liver failure, and major bleeding due to anti-FXa (anti-Xa) inhibitors (eg, rivaroxaban and apixaban). As transfusion of frozen plasma (FP) has not been found efficacious in the above critical bleeding scenarios, there is increasing interest in expanding the use of 4F-PCC. However, efficacy, safety, and clinical implications of expanded use of 4F-PCC have not been fully elucidated. Prothrombin time and international normalized ratio are commonly used to assess dose effects of 4F-PCC. Prothrombin time/international normalized ratio are standardly use for warfarin titration, but they are not suited for real-time monitoring of complex coagulopathies. Optimal dosing of 4F-PCC outside of the current approved use for vitamin K antagonist reversal is yet to be determined. In this review, we will discuss the use of 4F-PCC in four critical bleeding settings: cardiac surgery, major trauma, end-stage liver disease, and oral anti-Xa reversal. We will discuss recent studies in each area to explore the dosing, efficacy, and safety of 4F-PCC.

Hereditary Antithrombin Deficiency: A Balancing Act of Perioperative Hemostasis and Thromboprophylaxis-A Case Report.

Hereditary deficiency of antithrombin (AT) is associated with increased risk of venous thromboembolism (VTE), especially under the circumstances of stress, vascular injury, and immobilization associated with surgery. To date, there is no consensus on the use of perioperative anticoagulant bridging in the setting of hereditary thrombophilia. Balancing hemorrhagic and thrombotic risks associated with anticoagulant bridging and AT deficiency can be challenging to perioperative physicians. We present a case of a 65-year-old woman with inherited AT deficiency with history of multiple VTEs who was admitted for presurgical anticoagulant bridging before microvascular decompression craniotomy for trigeminal neuralgia.

The use of high-dose hydroxocobalamin for vasoplegic syndrome.

We describe a case of hypotension on cardiopulmonary bypass for coronary artery bypass grafting, double valve repairs, and patent foramen ovale closure. The patient experienced vasoplegic syndrome while on cardiopulmonary bypass. He was treated with high-dose hydroxocobalamin (vitamin B12). His blood pressure responded rapidly, obviating any further vasopressor requirements.