Strategy for Cardiovascular Surgery in Patients with Antithrombin III Deficiency

Nishimura, Yoshiyuki; Takagi, Yasushi

doi:10.5761/atcs.oa.18-00030

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…In 2013, Ranucci et al 9 reported that preoperative AT supplementation not only avoids excessive postoperative decrease in AT activity but also prevents heparin resistance. In 2018, Nishimura and Takagi 10 described that in AT-deficient patients who undergo cardiac surgery, it is important to perform AT replacement treatment to achieve preoperative AT activity ≥120% and postoperative AT activity ≥80%, while the activated clotting time is maintained at >400 seconds during cardiopulmonary bypass. In 1 patient (case 2) in our case series, the AT activity value was found to be low before the operation.…”

Section: Discussionmentioning

confidence: 99%

Multiple Thrombi during Microvascular Anastomosis Caused by Decreased Antithrombin Activity: A Case Report

Uchibori

Takanari

Nakamura

et al. 2020

Plastic and Reconstructive Surgery - Global Open

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Summary: With recent advances in microsurgical instruments and technique, microvascular anastomosis has become a universal surgical technique; however, thrombosis still presents in a number of cases. Tension, twisting, and compression to the anastomotic site are the main causes of thrombus; however, disorder of the coagulation–fibrinolysis system also need to be considered. To date, only few reports exist regarding thrombosis caused by disorder of coagulant system in microvascular anastomosis. Here we report our 3 cases in which multiple thrombus formation occurred intraoperatively caused by decrease of antithrombin (AT) activity. AT activity was measured twice a day after vascular anastomosis: after surgery and up to 3 days after surgery. Thrombosis was not observed in any of the 3 patients intraoperatively after the transfusion, or thrombosis was not observed in any of 3 patients intraoperatively after the transfusion or postoperatively, and no other complications were observed. In these 3 cases, the thrombus was not caused by technical error or other previously described factors. The observed intraoperative decrease in AT activity was thought to be caused by thrombus formation. It is important that microsurgeons are reminded that disorders of the coagulation–fibrinolysis system could cause thrombosis.

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Section: Discussionmentioning

confidence: 99%

Multiple Thrombi during Microvascular Anastomosis Caused by Decreased Antithrombin Activity: A Case Report

Uchibori

Takanari

Nakamura

et al. 2020

Plastic and Reconstructive Surgery - Global Open

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“…THROMBATE III (antithrombin III [human]) is a human plasma‐derived antithrombin III (AT) product indicated for prevention of thrombosis during surgical or obstetric procedures or for the treatment of thrombosis in patients with hereditary AT deficiency 1 . While inherited AT deficiency is uncommon, reduced AT activity in patients on extracorporeal life support is not, especially with prolonged heparin exposure 2,3 . AT measurement and replacement have become common practices in neonatal and paediatric extracorporeal membrane oxygenation (ECMO), despite a lack of robust evidence on efficacy and safety of pooled or recombinant AT 4–6 .…”

Section: Introductionmentioning

confidence: 99%

“…exposure. 2,3 AT measurement and replacement have become common practices in neonatal and paediatric extracorporeal membrane oxygenation (ECMO), despite a lack of robust evidence on efficacy and safety of pooled or recombinant AT. [4][5][6] The 2021 Extracorporeal Life Support Organization (ELSO) guidelines for anticoagulation during ECMO infer that monitoring of AT has a strong pharmacologic rationale when using unfractionated heparin (UFH) and recommend considering AT replacement if on maximum dose of UFH and unable to obtain anticoagulation goals, with a goal AT activity of >50%-80%.…”

mentioning

confidence: 99%

Evaluation of acquired antithrombin deficiency in paediatric patients supported on extracorporeal membrane oxygenation

Procaccini

Roem

et al. 2023

Brit J Clinical Pharma

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Investigator Statement", "What is already known about this subject" and "What this study adds" sections have been corrected in this version.]Aims: There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose-response in paediatric extracorporeal membrane oxygenation (ECMO) patients. Methods:We conducted a retrospective cohort study at a quaternary care paediatric intensive care unit in all patients <18 years of age supported on ECMO from 1 June 2011 to 30 April 2020. Adverse events and outcomes were characterized for all ECMO runs. AT activity and replacement were characterized and compared between two clinical protocols. AT activities measured post-vs. pre-AT replacement were compared in order to characterize a dose-response relationship. Results:The final cohort included 191 patients with 201 ECMO runs and 2028 AT activity measurements. The median AT activity was 65% (interquartile range [IQR], 51-82) and 879 (43.3%) measurements met the criteria of deficient. The overall median AT dose and increase in AT activity were 50.6 units/kg/dose (IQR, 39.5-67.2) and 23.5% (IQR, 9.8-36.0), respectively. In the protocol that restricted AT activity measurements to clinical scenarios concerning for heparin resistance, there was significantly higher dosing in conjunction with significantly fewer overall administrations. Approximately one third of AT activity remained deficient after repletion.There was no difference in mechanical complications, reasons for discontinuation of ECMO support, time on ECMO or survival between protocols.Conclusions: There was a high prevalence of AT deficiency in paediatric ECMO patients. An AT replacement protocol based on evaluating heparin resistance is associated with fewer AT administrations, with similar circuit and patient outcomes.Further data are needed to identify optimal dosing strategies.

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“…4 –6 While inherited AT deficiency is rarely encountered in cardiac surgery patients, it is not uncommon for reduced levels of AT activity to occur, especially in patients who experience prolonged heparin exposure. 5,7 When this occurs patients may develop an acquired AT deficiency, which has been identified as a heparin resistance, resulting in subclinical anticoagulation. Inadequate control of coagulation may further disrupt hemostasis through the activation and consumption of various elements of the coagulation system, resulting in excessive bleeding and inflammation.…”

Section: Introductionmentioning

confidence: 99%

Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery

Stammers¹,

Francis²,

Miller³

et al. 2020

Perfusion

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The maintenance of anticoagulation in adult patients undergoing cardiopulmonary bypass is dependent upon a number of factors, including heparin concentration and adequate antithrombin activity. Inadequate anticoagulation increases the risk of thrombosis and jeopardizes both vascular and extracorporeal circuit integrity. The purpose of this study was to evaluate a goal-directed approach for the use of antithrombin in patients who were resistant to heparin. Following institutional review board approval, data were obtained from quality improvement records. A goal-directed protocol for antithrombin was established based upon heparin dosing (400 IU kg−1 body weight) and achieving an activated clotting time of ⩾500 seconds prior to cardiopulmonary bypass. Two groups of patients were identified as those receiving antithrombin and those not receiving antithrombin. Outcome measures included activated clotting time values and transfusion rates. Consecutive patients (n = 140) were included in the study with 10 (7.1%) in the antithrombin group. The average antithrombin dose was 1,029.0 ± 164.5 IU and all patients had restoration to the activated clotting time levels. Patients in the antithrombin group were on preoperative heparin therapy (80.0% vs. 24.6%, p = 0.001). Prior to cardiopulmonary bypass the activated clotting time values were lower in the antithrombin group (417.7 ± 56.1 seconds vs. 581.1 ± 169.8 seconds, p = 0.003). Antithrombin patients had a lower heparin sensitivity index (0.55 ± 0.17 vs. 1.05 ± 0.44 seconds heparin−1 IU kg−1, p = 0.001), received more total heparin (961.3 ± 158.5 IU kg−1 vs. 677.5 ± 199.0 IU kg−1, p = 0.001), more cardiopulmonary bypass heparin (22,500 ± 10,300 IU vs. 12,100 ± 13,200 IU, p = 0.016), and more protamine (5.4 ± 1.2 vs. 4.1 ± 1.1 mg kg−1, p = 0.003). The intraoperative transfusion rate was higher in the antithrombin group (70.0% vs. 35.4%, p = 0.035), but no differences were seen postoperatively. Utilization of a goal-directed algorithm for the administration of antithrombin for the treatment of heparin resistance is effective in patients undergoing cardiac surgery.

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Strategy for Cardiovascular Surgery in Patients with Antithrombin III Deficiency

Cited by 8 publications

References 10 publications

Multiple Thrombi during Microvascular Anastomosis Caused by Decreased Antithrombin Activity: A Case Report

Multiple Thrombi during Microvascular Anastomosis Caused by Decreased Antithrombin Activity: A Case Report

Evaluation of acquired antithrombin deficiency in paediatric patients supported on extracorporeal membrane oxygenation

Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery

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