Thrombin generation and fibrin clot formation under hypothermic conditions: An in vitro evaluation of tissue factor initiated whole blood coagulation

Whelihan, Matthew F.; Kiankhooy, Armin; Brummel‐Ziedins, Kathleen E.

doi:10.1016/j.jcrc.2013.10.010

Cited by 20 publications

(20 citation statements)

References 39 publications

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“…По этим причинам в последнее время возрос интерес к так называемым «глобальным» методам изучения состояния системы гемостаза, потому что возник дисбаланс между пониманием физиологии процесса свёртывания и данными стандартных коагулологических исследований. Наиболее значимые из них -тест генерации тромбина, тромбоэластография (ТЭГ), низкочастотная пьезотромбоэластография (НПТЭГ) и тромбодинамика [11][12][13][14].…”

unclassified

“…Тест генерации тромбина впервые был предложен в 1953 г. R. Macfarlane и R. Biggs для оценки состояния системы гемостаза у больных гемофилией, его проводили с цельной кровью. Позже, группа учёных под руководством Н. Hemker в 1990 г. переработала методику проведения теста, автоматизировала учёт образования тромбина в нескольких образцах плазмы крови [11,13,15,16].…”

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“…В частности, он весьма чувствителен к предварительно-аналитическому этапу подготовки образца, в том числе методу сбора, характеру материала пробирки, использованного антикоагулянта и аналитических показателей (уровня тканевого фактора, концентрации липидов, наличия хилёза). Результаты теста могут различаться даже в условиях одной и той же лаборатории [11,13,14].…”

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“…В основе метода лежит оценка увеличения вязкости крови по мере образования сгустка с одновременной регистрацией данного процесса [11,13,23]. Для проведения анализа необходим образец цитратной крови, взятый из вены.…”

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“…Тем не менее, остаётся открытым вопрос об оценке надёжности результатов. Чтобы увеличить надёжность результатов, необходимы несколько ежедневных калибровок и обученный персонал [11,13,21]. Кроме того, отечественными и зарубежными исследователями выделены и другие недостатки данного метода [11,13,21,24]:…”

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“Global” assays of hemostasis in modern obstetrical practice

et al. 2019

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It is known that during pregnancy, the hemostatic system, like the rest of the body's systems, undergoes certain changes: there is a gradual increase in the activity of coagulation unit of the hemostasis reaching a maximum before childbirth. However, if pregnancy is complicated by various hypertensive conditions, such as preeclampsia, an imbalance is observed in the hemostasis: against the background of an increase in the activity of coagulation link, depletion of anticoagulation factors and dysfunction of fibrinolytic system are observed. All these changes create a pathogenetic basis for the occurrence of severe thrombohemorrhagic complications that are fatal for both mother and fetus. Thus, the timely detection of these violations is an important task for modern obstetrics. Unfortunately, the applied screening methods for assessing the hemostasis system in practice provide extremely limited information: the tests have low sensitivity to hypercoagulation, as well as moderate to hypocoagulation, they do not allow to fully evaluate the dynamics of coagulation process in real time. In addition, when performing the same tests with reagents of different companies in the same patient, there may be a significant difference in the results. Disadvantages of screening tests became the reason for the search for a test to assess the functioning of the hemostatic system, which can reflect the complete picture of the state of blood coagulation system, and not of its individual links. Such tests are the so-called global tests for assessing the hemostatic system: thrombin generation test, thromboelastography, low-frequency piezothromboelastography and thrombodynamics. Each of the listed global tests has been successfully tested in obstetric and gynecological practice.

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“Global” assays of hemostasis in modern obstetrical practice

et al. 2019

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Alteration of fibrin hydrogel gelation and degradation kinetics through addition of azo dyes

Gandhi

Heinrich

Knoff

et al. 2021

J Biomedical Materials Res

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Fibrin is a degradable biopolymer with an excellent clinical safety profile. Use of higher mechanical strength fibrin hydrogels is limited by the rapid rate of fibrin polymerization. We recently demonstrated the use of higher mechanical strength (fibrinogen concentrations >30 mg/ml) fibrin scaffolds for surgical implantation of cells. The rapid polymerization of fibrin at fibrinogen concentrations impaired our ability to scale production of these fibrin scaffolds. We serendipitously discovered that the azo dye Trypan blue (TB) slowed fibrin gelation kinetics allowing for more uniform mixing of fibrinogen and thrombin at high concentrations. A screen of closely related compounds identified similar activity for Evans blue (EB), an isomer of TB. Both TB and EB exhibited a concentration dependent increase in clot time, though EB had a larger effect. While gelation time was increased by TB or EB, overall polymerization time was unaffected. Scanning electron microscopy showed similar surface topography, but transmission electron microscopy showed a higher cross‐linking density for gels formed with TB or EB versus controls. Based on these data we conclude that addition of TB or EB during thrombin mediated fibrin polymerization slows the initial gelation time permitting generation of larger more uniform fibrin hydrogels with high‐mechanical strength.

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Hypothermic circulatory arrest at 20 ℃ does not deteriorate coagulopathy compared to 28 ℃ in a pig model

Ise,

Oyama,

Ushioda

et al. 2024

J Artif Organs

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It is believed that a lower temperature setting of hypothermic circulatory arrest (HCA) in thoracic aortic surgery causes coagulopathy, resulting in excessive bleeding. However, experimental studies that eliminate clinical factors are lacking. The objective of this study is to investigate the influence of the temperature setting of HCA on coagulation in a pig model. Ten pigs were divided into the following two groups: moderate temperature at 28 °C (group M, n = 5) or lower temperature at 20 °C (group L, n = 5). Two hours of HCA during a total of 4 h of cardiopulmonary bypass (CPB) were performed. Blood samples were obtained at the beginning (T1) and the end (T2) of the surgery, and coagulation capability was analyzed through standard laboratory tests (SLTs) and rotational thromboelastometry (ROTEM). In SLTs, hemoglobin, fibrinogen, platelet count, prothrombin time, and activated partial thromboplastin time were analyzed. In ROTEM analyses, clotting time and clot formation time of EXTEM, maximum clot firmness (MCF), and maximum clot elasticity (MCE) of EXTEM and FIBTEM were analyzed. Fibrinogen decreased significantly in both groups (group M, p = 0.008; group L, p = 0.0175) at T2, and FIBTEM MCF and MCE also decreased at T2. There were no differences regarding changes in parameters of SLTs and ROTEM between groups. CPB decreases coagulation capacity, contributed by fibrinogen. However, a lower temperature setting of HCA at 20 °C for 2 h did not significantly affect coagulopathy compared to that of HCA at 28 °C after re-warming to 37 °C.

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Thrombin generation and fibrin clot formation under hypothermic conditions: An in vitro evaluation of tissue factor initiated whole blood coagulation

Cited by 20 publications

References 39 publications

“Global” assays of hemostasis in modern obstetrical practice

“Global” assays of hemostasis in modern obstetrical practice

Alteration of fibrin hydrogel gelation and degradation kinetics through addition of azo dyes

Hypothermic circulatory arrest at 20 ℃ does not deteriorate coagulopathy compared to 28 ℃ in a pig model

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