Drug-drug interaction of the anti-TFPI aptamer BAX499 and factor VIII: Studies of spatial dynamics of fibrin clot formation in hemophilia A

Parunov, Leonid A.; Soshitova, Natalia P.; Fadeeva, Olga A.; Баландина, А. Н.; Kopylov, Konstantin G; Kumskova, Mariia; Gilbert, James C.; Schaub, Robert G.; McGinness, Kathleen E.; Ataullakhanov, Fazoil I.; Panteleev, Mikhail A.

doi:10.1016/j.thromres.2013.10.036

Cited by 16 publications

(6 citation statements)

References 28 publications

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“…The strong correlation between TFPI levels and TG potential in haemophilic patients is in accordance with other studies that showed that blocking TFPI restores TG potential in haemophilic patients, the correction of TG depending on the anti-TFPI antibody concentration. 25,26 Whether this major role of TFPI demonstrated at low TF concentrations would persist at high TF concentrations is a question that remains to be answered.…”

Section: Discussionmentioning

confidence: 99%

Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients

et al. 2019

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The thrombin generation (TG) assay evaluates haemostatic balance, which is influenced by the levels of many coagulation factors and inhibitors. Our objective was to identify the determinant factors of TG in haemophilia A (HA) and haemophilia B (HB) patients and to compare them to those in healthy controls. Coagulation factor and inhibitor levels, and TG, were measured in platelet‐poor plasma from 40 patients with HA, 32 patients with HB and 40 healthy subjects. Data were analysed using multiple regression models. In HA patients, factor VIII was a positive determinant of endogenous thrombin potential (ETP) and peak, whereas tissue factor pathway inhibitor (TFPI) and factor V were negative determinants of ETP and peak. In HB patients, FIX was a positive determinant of ETP and peak, FVII being a positive determinant of peak. Antithrombin and protein S (PS) were negative determinants of ETP while FX was a negative determinant of peak. Above all, in HB patients, TFPI was a negative determinant of ETP and peak. In healthy subjects, FVIII was a positive determinant of ETP and peak, whereas FX and protein S were negative determinants of these parameters. TFPI was not a negative determinant of either peak or ETP. In haemophilic patients, the determinant factors of TG are all implicated in FXa generation and inhibition, the crucial determinant factor being TFPI whatever the type of haemophilia, A or B. These findings contribute to the rationale that recently place TFPI as a target for innovative therapies of haemophilia.

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Section: Discussionmentioning

confidence: 99%

Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients

et al. 2019

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“…Some of the clinical and pharmacological results obtained with it are shown in Fig. 7, and more can be found in recent reports and reviews [67,[80][81][82][83][84][85][86].…”

Section: Spatial Coagulation: Possible Applications Beyond Basic Resementioning

confidence: 90%

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Panteleev

Dashkevich

Ataullakhanov

2015

Thrombosis Research

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“…О б з о р ы л и т е р а т у р ы тывания, таких как активированный фактор IX [18]. Возможность такого разделения причин гиперкоагуляции достигается за счет разделения фаз активации и распространения сгустка [25]. Модификация этого теста (тромбодинамика-4D) позволяет наравне с регистрацией фибрина проводить также регистрацию генерации тромбина [26].…”

Section: функциональные тестыunclassified

Аspects of the methodology of laboratory studies of hemostasis in pediatric hematology-oncology and general approaches in the pathology of hemostasis in leukemia

Koltsova¹,

Баландина²,

Seregina³

et al. 2018

Ross. ž. det. gematol. onkol.

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Children with acute leukemia are faced with high risks of thrombotic and hemorrhagic complications. The pathogenesis of haemostasis disorders in hemoblastoses is complex because, in addition to the disease itself, the aggressiveness of the therapy and the need for numerous invasive manipulations also make a significant contribution. Patients with hemoblastoses are equally susceptible to thrombosis and hemorrhage, which makes it possible to speak of multidirectional shifts in the balance of the hemostatic system in each individual patient. Standard laboratory hemostasis tests (clotting times, marker tests) are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostasis, and in do not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests designed to assess the coagulation balance, such as thromboelastography, thrombin generation test, and thrombodynamics, can be the alternative for the standard coagulation assays. The review focuses on the mechanisms of various laboratory hemostasis tests, as well as an assessment of their informative value in frequent complications of the underlying disease (sepsis leading to the development of disseminated intravascular coagulation (DIC) syndrome, thrombocytopenia) and catheterization, which is present in the majority of patients with hemoblastosis. General screening tests of the blood coagulation system have little diagnostic value in the DIC syndrome in patients with acute leukemia, mainly due to their insensitivity to hypercoagulability. Standard markers (for example, D-dimers) are non-specific and only confirm the clinical manifestations of clotting disorder in sepsis and septic shock, but are unable to predict the dynamics of this process at earlier stages of the inflammatory response. In this case, the thrombin generation test and thrombodynamics make it possible to reveal the hypercoagulable phase of the DIC syndrome. Thrombocytopenia accompanies almost all protocols of chemotherapy. In this case, the degree of bleeding does not always depend only on the concentration of platelets, since chemotherapeutic drugs can affect not only the quantity, but also the functional characteristics of platelets, which are not determined by standard examination of patients. The catheterization that accompanies the treatment of hemoblastoses is the leading cause of thrombosis in children with acute leukemia. Thromboembolism of the pulmonary artery due to thrombosis in the central vein system occurs in 8–15 % of patients. The prediction of catheter-associated thromboses using standard laboratory methods for assessing the state of the hemostasis is not possible. Absence of sensitive tests in modern diagnostic schemes leads to the fact that the attending physician is forced to focus exclusively on the clinical picture of thrombosis or bleeding. The development of new functional methods of hemostasis allows one to think that today the existing standard panel of coagulation tests can be expanded and made much more informative in terms of the prediction of thrombohemorrhagic complications in pediatric hematology-oncology.

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Drug-drug interaction of the anti-TFPI aptamer BAX499 and factor VIII: Studies of spatial dynamics of fibrin clot formation in hemophilia A

Cited by 16 publications

References 28 publications

Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients

Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Аspects of the methodology of laboratory studies of hemostasis in pediatric hematology-oncology and general approaches in the pathology of hemostasis in leukemia

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