Effects of tranexamic acid and exogenous fibrin monomer on the liver injury area and systemic circulation in pharmacological suppression of platelet function in an experiment

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Abstract

Aim. To identify and compare the morphological, hemostatic and hemostasiological consequences of intravenous administration of tranexamic acid and fibrin monomer in controlled liver injury against drug-induced thrombocytopathy.

Methods. The morphological features of fibrin formation in the area of liver injury after spontaneous bleeding arrest combined with the indicators of blood loss in the animals treated with intravenous placebo, tranexamic acid or fibrin monomer was studied in 69 male rabbits. The effects of these drugs were assessed against thrombocytopathy associated with the combined use of acetylsalicylic acid and clopidogrel. Platelet number and function (adnosine diphosphate-induced aggregation), the data of thromboelastometry and calibrated automated thrombogram, fibrinogen concentration and D-dimer level were considered in the blood test. The feature distribution in the samples was assessed using the Shapiro–Wilk test. Depending on the distribution, Student's t-test, Mann–Whitney U test or Wilcoxon signed-rank test were used to test for a significant difference between the features. Differences in mortality rate were established by using Fisher's exact test. The differences were considered statistically significant at p <0.05.

Results. A model of thrombocytopathy which showed decreased platelet aggregation function (by 4.5 times), increased blood loss (by 40%), and high mortality (53.9%) was reproduced. Only a small accumulation of thrombotic material was noted on the injured surface of such animals. The use of tranexamic acid led to decreased post-traumatic bleeding (2.5 times) and animal mortality (20%). The latter was provided on the wound surface by increasing the thickness of both thrombotic deposits and fibrin strands. When fibrin monomer was used, the phenomenon of an overcompensated decrease in blood loss (by 6.7 times) accompanied by zero mortality was noted despite a pronounced decrease in platelet aggregation. The maximum increase in the thickness of thrombotic material and fibrin strands was morphologically determined in the injury area compared with other animal groups.

Conclusion. Morphological features of traumatic hemostatic effect at the injured area when using tranexamic acid and fibrin monomer have a number of differences despite the similarity of the achieved results in minimizing blood loss.

About the authors

V M Vdovin

Altai State Medical University

Author for correspondence.
Email: erytrab@gmail.com
ORCID iD: 0000-0002-4606-3627
Russian Federation, Barnaul, Russia

A P Momot

Altai State Medical University; Altai Branch of FSBI National Research Center for Hematology

Email: xyzan@yandex.ru
ORCID iD: 0000-0002-8413-5484
Russian Federation, Barnaul, Russian; Barnaul, Russia

I I Shakhmatov

Altai State Medical University

Email: iish59@yandex.ru
ORCID iD: 0000-0002-0979-8560
Russian Federation, Barnaul, Russia

I P Bobrov

Altai State Medical University

Email: ig.bobrov2010@yandex.ru
Russian Federation, Barnaul, Russia

D A Orekhov

Altai Regional Dispensary of Cardiology

Email: orekhoffs@mail.ru
ORCID iD: 0000-0003-0644-6313
Russian Federation, Barnaul, Russian

V V Terjaev

Altai State Medical University

Email: teryaevw@yandex.ru
ORCID iD: 0000-0001-5968-3246
Russian Federation, Barnaul, Russia

V E Chernus'

Altai State Medical University

Email: chernus97@mail.ru
ORCID iD: 0000-0003-0800-4906
Russian Federation, Barnaul, Russia

D V Kuznetsova

Altai State Medical University

Email: kdvl17@gmail.com
Russian Federation, Barnaul, Russia

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Supplementary files

Supplementary Files
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1. JATS XML
2. Рис. 1. Дизайн экспериментов с дозированной травмой печени; АСК — ацетилсалициловая кислота; КЛ — клопидогрел; ТК — транексамовая кислота; ФМ — фибрин-мономер

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3. Рис. 2. Пример морфологической картины в области раны печени кролика первой группы (плацебо). А — тромботические отложения, окраска гематоксилином и эозином, увеличение ×100; В — нити фибрина в тромботических отложениях (показаны стрелками, F — фибрин), окраска на фибрин по ОКГ (оранжевый Ж, кислотный красный 2С и водный голубой), увеличение ×400; С — тромбоциты в просвете крупных сосудов в области раны (показаны стрелками, Plt — тромбоциты), окраска гематоксилином и эозином, увеличение ×1000

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4. Рис. 3. Пример морфологической картины в области раны печени кролика второй группы (антиагреганты и плацебо). А — тромботические отложения, окраска гематоксилином и эозином, увеличение ×100; В — нити фибрина в тромботических отложениях (показаны стрелками, F — фибрин), окраска на фибрин по ОКГ (оранжевый Ж, кислотный красный 2С и водный голубой), увеличение ×400; С — тромбоциты в просвете крупных сосудов в области раны (показаны стрелками, Plt — тромбоциты), окраска гематоксилином и эозином, увеличение ×1000

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5. Рис. 4. Пример морфологической картины в области раны печени кролика третьей группы (антиагреганты и транексамовая кислота). А — тромботические отложения, окраска гематоксилином и эозином, увеличение ×100; В — нити фибрина в тромботических отложениях (показаны стрелками, F — фибрин), окраска на фибрин по ОКГ (оранжевый Ж, кислотный красный 2С и водный голубой), увеличение ×400; С — тромбоциты в просвете крупных сосудов в области раны (показаны стрелками, Plt — тромбоциты), окраска гематоксилином и эозином, увеличение ×1000

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6. Рис. 5. Пример морфологической картины в области раны печени кролика четвёртой группы (антиагреганты и фибрин-мономер). А — тромботические отложения, окраска гематоксилином и эозином, увеличение ×100; В — нити фибрина в тромботических отложениях (показаны стрелками, F — фибрин), окраска на фибрин по ОКГ (оранжевый Ж, кислотный красный 2С и водный голубой), увеличение ×400; С — тромбоциты в просвете крупных сосудов в области раны (показаны стрелками, Plt — тромбоциты), окраска гематоксилином и эозином, увеличение ×1000

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