Gender-specific differences in haemostatic parameters and their influence on blood loss in bimaxillary surgery

Objective The objectives of this prospective cohort study were to establish gender-related differences in blood loss and haemostatic profiles associated with bimaxillary surgery. In addition, we aimed to identify if any gender differences could be established which might help predict blood loss volume. Materials and methods Fifty-four patients (22 males; 32 females) undergoing bimaxillary surgery for skeletal dentofacial deformities were eligible for inclusion. Blood samples were taken 1 day preoperatively and 48 h postoperatively for detailed gender-specific coagulation analysis incorporating global coagulation assays (endogenous thrombin potential) and specific coagulation parameters. Blood loss was measured at two different time points: (1) the end of surgery, visible intraoperative blood loss (IOB) using ‘subtraction method’; and (2) 48 h postoperatively perioperative bleeding volume (CBL-48 h) using ‘haemoglobin-balance method’ and Nadler’s formula. Correlation and regression analyses were performed to identify relevant parameters affecting the amount of blood loss. Results Significant differences in IOB and CBL-48 h were observed (p < 0.001). Men had higher IOB versus women, lacking statistical significance (p = 0.056). In contrast, men had significantly higher CLB-48 h (p = 0.019). Reduced CBL-48 h was shown to be most closely associated with the level of Antithrombin-III being decreased in females. Conclusions Male gender is associated with higher IOB and CBL-48 compared with females. Gender does not affect IOB regarding haemostatic profile but does correlate strongly with procedure length. Conversely, CBL-48 is closely associated with gender-specific imbalances in the anticoagulant system. Clinical relevance Knowledge of gender-related differences will help clinicians establish predictive factors regarding excessive blood loss in orthognathic surgery and identify at-risk patients.

COMPARATIVE ANALYSIS OF THE QUANTITATIVE AND QUALITATIVE METHOD FOR DETERMINATION OF D - DIMER

Introduction: D - dimer is a product released during the process of blood clotting and degradation, which can be measured by blood sample analysis. There is usually the minimal activity of the pro/anticoagulant system in the human body, which generates low levels of D-dimer in healthy individuals. Normal values for plasma D-dimer are ≤ 0.50 mg / l. Aim: The aim of the present study is to determine to what extent the quantitative and qualitative method for determination of D - dimer can be interchangeable and what is their diagnostic reliability in the normal and pathological area of measurement. Materials and methods: We studied the levels of D-dimer by two methods - quantitative and qualitative, in 91 patients aged 25 to 86 years, of which 59 men and 32 women. To determine the D-dimer, we used venous blood taken in a vacuette containing sodium citrate. We used a Roche test for quantitative determination and a Latex agglutination test for qualitative determination. Results: It was found that in positive samples above 0.5 mg/l, there is a very high percentage of coincidence. There is a discrepancy in the values obtained by the two methods at the negative values below 0.5 mg/l. We determined the sensitivity, specificity and accuracy of both methods. Conclusion: The correlation in the results of the two methods is very good, but the quantification of D-dimer is more specific and accurate. We recommend that the value of 0.5 mg/l should be used as a cut off value for D-dimer.

Association of acquired and congenital thrombophilic factors in a child with ischemic stroke

Введение. Тромбоз остается одной из ведущих причин летальности населения. В связи с этим остро стоит вопрос своевременной диагностики причин и анализа провоцирующих факторов возникновения тромботических событий, в особенности у детей с генетически детерминированной тромбофилией. Цель описания клинического случая: демонстрация роли мультифакторности генеза тромбоза в сочетании с патологическими состояниями, усиливающими гемостатическую активность крови в детском возрасте, для дальнейшего прогнозирования развития ребенка и определения методов профилактики рецидивов тромботических осложнений во взрослом возрасте. Результаты. Мальчик А., в возрасте 7 лет перенес острое нарушение мозгового кровообращения по ишемическому типу от 25.08.16, которому предшествовала ревакцинация корь-паротит-краснуха , острый гастроэнтерит с эксикозом II степени, токсикозом и длительным периодом иммобилизации в течение 2 нед. На момент тромботического события установлена гипергомоцистеинемия (10 мкмоль/л при референсных значениях возрастной нормы 3,05,0 мкмоль/л). При выполнении молекулярно-генетического исследования выявлено 5 гетерозиготных полиморфизмов минорного риска тромбоза (MTHFR, MTRR, PAI1, FGB, ITGA22). На момент последней госпитализации (февраль 2019 г.) обнаружено снижение эффективности работы системы естественных антикоагулянтов по результатам теста генерации тромбина, а также умеренное снижение активности антикоагулянта протеина С до 74 (при нижней границе нормы 75). Заключение. Мультифакторность тромбоза у детей предусматривает комплексный подход к диагностике и лечению, а также профилактике рецидивов тромботического события с обязательным контролем в динамике состояния системы гемостаза, уровня естественных антикоагулянтов и гомоцистеина. Introduction. Thrombosis remains one of the leading causes of mortality in the population. Thereby the timely diagnosis and analysis of the triggering factors of thrombotic events, especially in cases of genetically determined thrombophilia in children is acute question. Aim: to demonstrate the role of the multifactor genesis of thrombosis in combination with pathological conditions that enhanced blood hemostatic activity in childhood, for further prediction and prophylaxis of recurrence of thrombotic events in adulthood. Results. Patient A. had an ischemic stroke when he was 7 years old. It was preceded by rubeola-parotitis-rubella revaccination, acute gastroenteritis with degree II excision, toxicosis and a long period of immobilization for 2 weeks. Hyperhomocysteinemia was revealed (10 mol/L, reference values of the age norm are 3.05.0 mol/L) at the time of the thrombotic event. Molecular genetics study identified 5 heterozygous polymorphisms of a minor risk of thrombosis (MTHFR, MTRR, PAI1, FGB, ITGA22). At the date of last hospitalization (February 2019) decreased efficiency of anticoagulant system (according to the results of the thrombin generation assay) and moderate decreasing of protein C activity to 74 (with a lower normal limit of 75) were found. Conclusion. The multifactorial nature of thrombosis in children provides an integrated approach to the diagnosis, treatment and prophylaxis of recurrence of thrombotic events with monitoring of hemostasis, levels of natural anticoagulants and homocysteine.

Association of Thrombomodulin Gene C1418T Polymorphism with Susceptibility to Kawasaki Disease in Chinese Children

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children and can result in coronary artery lesions (CALs). Thrombomodulin (TM) is a critical cofactor in the protein C anticoagulant system. The TM C1418T (rs1042579) polymorphism is associated with a high risk of cardiac-cerebral vascular diseases. But the association of the TM C1418T polymorphism with susceptibility to KD, CAL formation, and intravenous immunoglobulin (IVIG) resistance is still unclear. In our study, we examined the TM C1418T polymorphism in 122 children with KD and 126 healthy children and revealed the correlation between the TM C1418T polymorphism and KD, CAL formation, and IVIG resistance.

REGULATION OF HEMOSTASIS FUNCTIONS BY GLYPROLIN PEPTIDES AT METABOLIC SYNDROME IN RATS

Цель исследования: изучение влияния регуляторных пептидов глипролинового ряда на состояние системы гемостаза в условиях in vivo на модели крыс с экспериментальным метаболическим синдромом (МС). Материалы и методы. Эксперимент проводили на 60 беспородных белых крысах-самцах с массой тела 200±10 г в возрасте 2 месяца к началу опыта (к началу кормления высококалорийным рационом — ВКР). Развитие экспериментального МС у животных вызывали содержанием их на ВКР с избыточным содержанием углеводов и насыщенных жиров. Исследовали влияние интраназального многократного (7 раз) введения в малых дозах (50 мкг/кг) регуляторных пептидов Pro-Leu-Pro, Pro-Leu-Pro-Ala, Pro-Gly-Pro-Ala и Phe-Pro-Leu-Pro-Ala животным с МС на систему свертывания крови и фибринолиз. Результаты. Через 20 часов после последнего введения пептидов наблюдалось усиление антикоагулянтной и суммарной фибринолитической активности плазмы, обусловленной как повышением неферментативного, так и ферментативного фибринолиза плазмы, а также снижение агрегации тромбоцитов. Все исследованные пептиды обладали пролонгированным действием и способностью активировать функцию противосвертывающей системы. Заключение. Максимальный противосвертывающий эффект проявляли два пептида — Pro-Leu-Pro-Ala и Phe-Pro-Leu-Pro-Ala, причем в период после отмены их применения достоверность и значимость их эффектов возрастали. Aim: to study the eff ect of glyproline regulatory peptides on hemostasis in vivo in the model of experimental metabolic syndrome (MS) in rats. Materials and methods. The experiment was carried at 60 outbred white male rats with a body weight of 200±10 g and 2 months age at the beginning of the experiment (at the beginning of feeding with a high caloric diet — HCD). The development of experimental MC in animals was caused by HCD with an excess of carbohydrates and saturated fats. We examined the effects of intranasal repeated (7 times) administration of regulatory peptides Pro-Leu-Pro, Pro-Leu-Pro-Ala, Pro-Gly-Pro-Ala and Phe-Pro-Leu-Pro-Ala in low doses (50 μg/kg) on blood coagulation and fibrinolysis in animals with MC. Results. We revealed the enhancement of anticoagulant blood activity and total fibrinolytic activity caused by increasing of non-enzymatic and enzymatic fibrinolysis, and decreasing of platelet aggregation 20 hours after the last peptides administration. All studied peptides had prolonged action and the ability to activate anticoagulant system. Conclusion. Peptides Pro-Leu-Pro-Ala and Phe-Pro-Leu-Pro-Ala showed the maximum anticoagulant effect, and after stopping of their application the reliability and signifi cance of their effects increased.

Malignant Hematologic Disorders

The 2 essential functions of the coagulation system (maintaining hemostasis and preventing and limiting thrombosis) are served by the procoagulant and anticoagulant components. Vascular injury results in activation of the phases of hemostasis, including vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system controls excessive clot formation, while the fibrinolytic system breaks down and remodels blood clots.

A hereditary bleeding disorder resulting from a premature stop codon in thrombomodulin (p.Cys537Stop)

Key Points A novel TM mutation results in shedding of active TM into the blood. Subsequent activation of the protein C anticoagulant system causes bleeding.