ABSTRACT
Population pharmacokinetic (pop-PK) models constructed for model-informed precision dosing often have limited utility due to the low number of patients recruited. To augment such models, an approach is presented for generating fully artificial quasi-models which can be employed to make individual estimates of pharmacokinetic parameters. Based on 72 concentrations obtained in 12 patients, one- and two-compartment pop-PK models with or without creatinine clearance as a covariate were generated for piperacillin using the nonparametric adaptive grid algorithm. Thirty quasi-models were subsequently generated for each model type, and nonparametric maximum a posteriori probability Bayesian estimates were established for each patient. A significant difference in performance was found between one- and two-compartment models. Acceptable agreement was found between predicted and observed piperacillin concentrations, and between the estimates of the random-effect pharmacokinetic variables obtained using the so-called support points of the pop-PK models or the quasi-models as priors. The mean squared errors of the predictions made using the quasi-models were similar to, or even considerably lower than those obtained when employing the pop-PK models. Conclusion: fully artificial nonparametric quasi-models can efficiently augment pop-PK models containing few support points, to make individual pharmacokinetic estimates in the clinical setting.
ABSTRACT
Acquired hemophilia A is a rare condition with the capability of bringing about life-threatening bleeding in the perioperative period, posing a significant challenge for the caregiver anesthetist to identify the underlying cause. However, a quick diagnosis might be supported by viscoelastometry by raising the suspicion of severe and isolated deficiency of the intrinsic coagulation pathway, requiring a prompt consultation with a hematology center. Special laboratory tests of hemostasis are helpful in the differential diagnosis of the detected coagulation disorder. Nevertheless, bypassing agents have gained a crucial role in the treatment of major perioperative blood losses by bypassing Factor VIII inactivated by autoantibodies and thus, initiating coagulation. Early goal-directed supplementation of depleted coagulation factors must also be kept in the focus of the therapy. Orv Hetil. 2023; 164(40): 1600-1604.
Subject(s)
Hemophilia A , Humans , Hemophilia A/diagnosis , Diagnosis, Differential , Blood Coagulation , AnesthesiologistsABSTRACT
Liver diseases result in a re-balanced state of the haemostatic system with decreased haemostatic reserves. Increased fibrinolytic activity is commonly seen during liver transplants. The aim of this study was to assess whether ClotPro's ECA-test is able to detect hyperfibrinolysis earlier and with higher frequency than ClotPro's conventional viscoelastic assays for the intrinsic and the extrinsic coagulation pathway. From 25 liver transplant recipients, systemic blood samples were collected during surgery. Viscoelastic haemostatic assays with ClotPro's IN-test, EX-test and ECA-test were performed simultaneously from each blood sample. Hyperfibrinolysis was defined on the basis of the manufacturer's prespecified threshold value (maximal lysis >15%). The incidence of hyperfibrinolysis detected with each test was compared with the McNemar test. For each assay, lysis detection time (LDT) was calculated and analysed with the nonparametric Kruskal-Wallis test. A total of 125 tests were performed simultaneously. Compared with the IN-test and the EX-test, the ECA-test detected hyperfibrinolysis in significantly ( P â<â0.001) higher number of patients (9; 11; 14, respectively) and in more measurement points (14; 18; 28, respectively). The analysis of LDT values revealed significant superiority of the ECA-test to the IN-test ( P â=â0.046) and to the EX-test ( P â=â0.035), indicating the profibrinolytic state of the haemostasis 8.9â±â0.65 and 8.7â±â0.17âmin earlier, respectively. These are preliminary results of the study NCT0424637. ClotPro's ECA-test appeared to detect fibrinolysis in a higher number of patients, more frequently, and the mean time of detection was 9âmin earlier than that of the IN-test and the EX-test.
Subject(s)
Blood Coagulation Disorders , Hemostatics , Humans , Blood Coagulation Disorders/diagnosis , Fibrinolysis , Blood Coagulation Tests , Fibrin Clot Lysis TimeABSTRACT
INTRODUCTION: International data indicate that arterial, venous and microvascular thrombosis or disseminated intravascular coagulation occur in more than 30% of hospitalized patients with COVID-19. This condition is characterized by high levels of D-dimer and fibrinogen, prolonged prothrombin time and activated partial thromboplastin time. METHOD: Blood samples from three COVID-19 patients treated in a Hungarian intensive care unit were collected and analyzed with ClotPro® tests. EX-tests, IN-test, FIB-tests, RVV-tests, and TPA-tests were performed. The results were interpreted with respect to the clinical condition of the patients. RESULTS: Procoagulation, hypercoagulation and either fibrinolysis or a "shut down" phenomenon of the fibrinolytic process were found with ClotPro®. The ClotPro® parameters were consistent with the conventional coagulation tests and corresponded with the criteria of non-overt disseminated intravascular coagulation. CONCLUSION: These findings encourage further investigations to elucidate the underlying pathophysiology of thromboembolic events in COVID-19 patients and may support the introduction of full dose anticoagulation with or without antiplatelet therapy. Interventional clinical trials may be helpful in defining the appropriate drug(s), for this purpose, the algorithms of administration, and the optimal duration of therapy. At present, the authorization of a clinical trial that attempts to answer these questions is in progress. Orv Hetil. 2020; 161(22): 899-907.
