Pharmacokinetics of human antithrombin III concentrate in the immediate postoperative period after liver transplantation

Kim, Bo Rim; Oh, Jaeseong; Yu, Kyung‐Sang; Ryu, Ho Geol

doi:10.1111/bcp.14200

Cited by 4 publications

(7 citation statements)

References 32 publications

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“…We next provide a series of analyses characterizing the exposure patterns of anticoagulant and antiplatelet agents over a 72‐h window post‐transplant and study their relationship to HAT rates across the aggregate, institutional‐, and patient‐level. Although we recognize that therapeutic antithrombotic protocols can extend beyond 72 h, in line with existing works this time threshold was set to limit the capture of additional medications that might be used as treatment for thrombosis, and not as prophylaxis 21 . As a specific timestamp of the transplant was not available on the date of service, the analysis was focused on the three absolute days following the procedure to aid in standardizing opportunity to receive medications.…”

Section: Methodsmentioning

confidence: 99%

“…Although we recognize that therapeutic antithrombotic protocols can extend beyond 72 h, in line with existing works this time threshold was set to limit the capture of additional medications that might be used as treatment for thrombosis, and not as prophylaxis. 21 As a specific timestamp of the transplant was not available on the date of service, the analysis was focused on the three absolute days following the procedure to aid in standardizing opportunity to receive medications. For reference the transplant day was defined as T 0 , and the subsequent 72 h were denoted as T 24, T 48, and T 72 , respectively.…”

Section: Medication Profilesmentioning

confidence: 99%

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Hepatic artery thrombosis and use of anticoagulants and antiplatelet agents in pediatric liver transplantation

Feldman,

Heble,

Hendrickson

et al. 2023

Pediatric Transplantation

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BackgroundHepatic artery thrombosis (HAT) is a reported complication of 5%–10% of pediatric liver transplantations, rates 3–4 times that seen in adults. Early HAT (seen within 14 days after transplant) can lead to severe allograft damage and possible urgent re‐transplantation. In this report, we present our analysis of HAT in pediatric liver transplant from a national clinical database and examine the association of HAT with anticoagulant or antiplatelet medication administered in the post‐operative period.MethodsData were obtained from the Pediatric Health Information System database maintained by the Children's Hospital Association. For each liver transplant recipient identified in a 10‐year period, diagnosis, demographic, and medication data were collected and analyzed.ResultsOur findings showed an average rate of HAT of 6.3% across 31 centers. Anticoagulant and antiplatelet medication strategies varied distinctly among and even within centers, likely due to the fact there are no consensus guidelines. Notably, in centers with similar medication usage, HAT rates continue to vary. At the patient level, use of aspirin within the first 72 h of transplantation was associated with a decreased risk of HAT, consistent with other reports in the literature.ConclusionWe suggest that concerted efforts to standardize anticoagulation approaches in pediatric liver transplant may be of benefit in the prevention of HAT. A prospective multi‐institutional study of regimen—possibly including aspirin—following transplantation could have significant value.

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Section: Methodsmentioning

confidence: 99%

Section: Medication Profilesmentioning

confidence: 99%

Hepatic artery thrombosis and use of anticoagulants and antiplatelet agents in pediatric liver transplantation

Feldman,

Heble,

Hendrickson

et al. 2023

Pediatric Transplantation

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“…Consequently, we performed a preceding study that retrospectively analyzed the pharmacokinetics of AT‐III in liver transplantation recipients and showed simulations of various dosing scenarios according to the developed model. According to the simulations, the plasma AT‐III activity level was expected to be maintained more stably within the target range (80%–120%) with a smaller total dose by the continuous infusion method with a loading dose than by the conventional intermittent infusion method 12 …”

Section: Introductionmentioning

confidence: 99%

“…According to the simulations, the plasma AT-III activity level was expected to be maintained more stably within the target range (80%-120%) with a smaller total dose by the continuous infusion method with a loading dose than by the conventional intermittent infusion method. 12 Therefore, a randomized controlled trial (RCT) was performed to compare the two AT-III administration methods in liver transplantation recipients. We hypothesized that the continuous infusion method of AT-III…”

Section: Introductionmentioning

confidence: 99%

Continuous versus intermittent infusion of human antithrombin III concentrate in the immediate postoperative period after liver transplantation

Kim

Lim

Choi

et al. 2023

Clinical Translational Sci

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Antithrombin-III (AT-III) concentrates have been used in the immediate postoperative period after liver transplantation to prevent critical thrombosis. We aimed to investigate a more appropriate method for AT-III concentrate administration to maintain plasma AT-III activity level within the target range. In this randomized controlled trial, 130 adult patients undergoing living-donor liver transplantation were randomized to either the intermittent group or continuous group. In the intermittent group, 500 international units (IU) of AT-III concentrate were administered after liver transplantation and repeated every 6 h for 72 h.In the continuous group, 3000 IU of AT-III were continuously infused for 71 h after a loading dose of 2000 IU over 1 h. Plasma AT-III activity level was measured at 12, 24, 48, 72, and 84 h from the first AT-III administration. The primary outcome was the target (80%-120%) attainment rate at 72 h. Target attainment rates at other timepoints and associated complications were collected as secondary outcomes. A total of 107 patients were included in the analysis. The target attainment rates at 72 h post-dose were 30% and 62% in the intermittent group and continuous group, respectively (p = 0.003). Compared to the intermittent group, patients in the continuous group reached the target level more rapidly (12 vs. 24 h, median time, p < 0.001) and were more likely to remain in the target range until 84 h. For maintaining the target plasma AT-III activity level after livingdonor liver transplantation, continuous infusion of AT-III seemed to be more appropriate compared to the conventional intermittent infusion regimen.How to cite this article: Kim BR, Lim L, Choi Y, et al. Continuous versus intermittent infusion of human antithrombin III concentrate in the immediate postoperative period after liver transplantation.

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“…Notably, CRP values have been used to predict the outcome of depression and resistance to standard antidepressants (32)(33)(34). ATIII is a glycoprotein mainly produced in the liver that exerts anticoagulant and anti-inflammatory effects by targeting activated thrombin and other blood coagulation factors (35,36). In addition, ATIII can promote prostacyclin release and deactivate leukocytes to inhibit inflammation independent from coagulation (36).…”

Section: Introductionmentioning

confidence: 99%

Potential of Antithrombin III as a Biomarker of Antidepressive Effect in Major Depressive Disorder

Song

Shi

et al. 2021

Front. Psychiatry

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Background: The evaluation of treatment response to antidepressant therapy commonly depends on neuropsychologic assessments, as there are currently no suitable biomarkers. Previous research has identified a panel of increased proteins in patients with major depressive disorder (MDD), including antithrombin III (ATIII), as potential biomarkers of depression.Methods: A total of 90 MDD patients were recruited. Of these, 74 patients received occipital repetitive transcranial magnetic stimulation (rTMS) as individualized, standard, or sham treatment for 5 days, and underwent the complete procedure, including clinical assessments, blood collection, and protein measurement.Results: After treatment, ATIII was significantly decreased in both the individualized and standard groups (both p < 0.001) relative to the sham group. In the individualized group, reduction in ATIII was associated with improvements in several neuropsychological assessments. Furthermore, ATIII at baseline in the standard group and after individualized rTMS showed good performance for evaluating or predicting the response to five-day treatment (AUC = 0.771, 95% CI, 0.571–0.971; AUC = 0.875, 95% CI, 0.714–1.000, respectively) and remission at follow-up (AUC = 0.736, 95% CI, 0.529–0.943; AUC = 0.828, 95% CI, 0.656–1.000, respectively). Lastly, both baseline ATIII and change in ATIII showed good predictive value for the 24-item Hamilton Depression Rating Scale at follow-up (p = 0.024 and 0.023, respectively).Conclusion: Our study revealed a reduction in ATIII after occipital rTMS in MDD patients and a relationship between change in ATIII and therapeutic response. Taken together, these findings provide evidence for the potential of ATIII as a biomarker for the evaluation and prediction of antidepressive effects.

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Pharmacokinetics of human antithrombin III concentrate in the immediate postoperative period after liver transplantation

Cited by 4 publications

References 32 publications

Hepatic artery thrombosis and use of anticoagulants and antiplatelet agents in pediatric liver transplantation

Hepatic artery thrombosis and use of anticoagulants and antiplatelet agents in pediatric liver transplantation

Continuous versus intermittent infusion of human antithrombin III concentrate in the immediate postoperative period after liver transplantation

Potential of Antithrombin III as a Biomarker of Antidepressive Effect in Major Depressive Disorder

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