Soluble Fibrin Monomer Complexes Research Articles

Ранний прогноз риска преэклампсии с учетом зрительных расстройств и изменений системы гемостаза

Aim: to analyze subjective and objective parameters of eye functioning and evaluate the role of hemostasis abnormalities for shaping groups of high risk for preeclampsia. Patients and Methods: 58 women were examined (history taking, eye and obstetric-gynecological exams, lab tests) to assess their ocular, somatic, and reproductive status and pregnancy course in the third trimester. Twenty-five women were diagnosed with preeclampsia: 13 women without ametropia at baseline were included in group 2, and 12 women with myopia prior to pregnancy were included in group 3. Controls were pregnant women without preeclampsia, i.e., 18 women with healthy pregnancy but no myopia, and 15 pregnant women without preeclampsia but with myopia. In addition, fibrinogen, activated partial thromboplastin time (APTT), soluble fibrin monomer complex (SFMC), and platelets were measured. Results: subjective and objective symptoms of visual disorders in pregnant women associated with hemostatic abnormalities were identified. These signs are considered preeclampsia predictors. The history of reproductive loss, headaches, and visual disorders during pregnancy are typical for preeclampsia women. Most susceptible individuals are women with preeclampsia and myopia who present with complaints of floaters, scotomas, photopsia, and diplopia. These signs illustrate vascular ischemia. Other relevant parameters are reduced platelet count (p<0.01) and APTT (p<0.01), and increased fibrinogen (p<0.01) and SFMC (p<0.002). Conclusion: careful diagnosis of cerebral neurological signs and visual disorders allows for timely diagnostic search and valid peripheral blood and hemostasis testing to improve management of these women and shape risk groups of preeclampsia without lethal complications. KEYWORDS: eye, eye fundus, myopia, photopsia, scotoma, diplopia, reproductive loss, preeclampsia, hemostasis. FOR CITATION: Kudinova E.G., Mozharina K.I. Early prognosis of preeclampsia risk based on visual disorders and hemostatic abnormalities. Russian Journal of Woman and Child Health. 2022;5(2):100–105 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-100-105

PROGNOSIS AND PREVENTION OF UTERUS BLEEDINGS IN EARLY POSTPARTUM PERIOD FOR WOMEN WITH IDIOPATHIC ARTERIAL HYPOTENSION

The aim: To establish the effectiveness of thromboelastography (TEG) and tranexamic acid (TXA) for prognosis and prevention of early postpartum period bleedings (PPB) for postpartum women with idiopathic arterial hypotension (IAH). Materials and methods: Coagulogical research was conducted (coaugologram screening, dynamic function of platelets under the influence of adenosine diphosphate (ADP) (visual assessment), measurement of soluble fibrin-monomer complexes (FMC) and TEG of 36 in parturient women during the I chilbirth period with arterial hypotension. 14 parturient women with normal fibrinolysis were included into the first observation group; The second group includes 22 parturient women with TEG results which show signs of hyperfibrinolysis. Further, in cases when stronger fibrinolysis was detected during the late pushing phase of childbirth period, the TXA by amount of 1,0 g IV (bolus) was injected due to bleeding prevention. TEG was repeated during early postpartum period. Results: the inhibition of platelet aggregation activity with ADP was observed in every parturient woman with IAH in the first partum period. In 61,1% cases with TEG hyperfibrinolysis were shown, which was accompanied by significant increase in FMC levels in blood. The use of TXA as PPB prevention for parturient women with IAH and hyperfibrinolysis during TEG was fully oppressing the fibrinolytic activity and was not affecting the coagulation part of hemostasis. Conclusions: hemostasis testing during childbirth based on TEG gives the ability to prognose the hemorrhagic complications in parturient women with IAH and administer their prophylaxy using TXA.

The Rise of Factor X Level in Blood Plasma of Patients at Severe Burn Injuries.

This work is dedicated to the detection of imbalance between the pro- and anticoagulant branches of hemostasis at severe burn injuries by evaluating the content or activity of individual clotting factors. To select the targets for accurate diagnostics we measured the concentrations of soluble fibrin monomeric complexes and fibrinogen, levels of total prothrombin, factor X, protein C, and antithrombin III, and recorded the time of clotting in activated partial thromboplastin time and prothrombin time (PT) tests. Factor X level was increased in 26% of patients on the 1st day after the burn and it rose further in 62% patients on the 14th day of recovery. Increasing factor X level is assumed to be a risk factor of thrombotic complications. We propose to use it as a marker of predisposition to thrombosis at severe burn injury.

COMPARATIVE ANALYSIS OF THE EFFECT OF HORMONE-INDUCED STRESS ON HEMOSTASIS IN THE CYPRINUS CARPIO AND THE OREOCHROMIS NILOTICUS

Background: The mortality of freshwater fish due to stress during various production manipulations is a severe problem, which requires a thorough understanding of the basic mechanisms involved, including the hemostasis system. Therefore, on the application level, the study of blood clotting can perform fish coagulopathies diagnostics and develop practical preventive and therapeutic anticoagulation methods for fish farming. Aim: The goal of this research was a comparative assessment of the reaction of some hemostasis parameters of two commercial fish species, carp Cyprinus carpio and tilapia Oreochromis niloticus, to the stress of different duration induced by corticosteroids. Methods: The fishes were divided into three groups: chronically stressed (induction by betamethasone), acutely stressed (induction by dexamethasone), and control animals with blood taken from the caudal hemal canal before hormone treatment(by dexamethasone and betamethasone), then 7 and 21 days after. Results and Discussion: Changes in the following parameters were studied: thrombin time, prothrombin time, activated partial thromboplastin time, the concentration of fibrinogen, soluble fibrin monomer complexes, antithrombin. It was found that both hormone-induced stress and handling stress associated with blood sampling strongly increased blood clotting ability in carps (prothrombin time decrease by 78,5-86,1%, fibrinogen increase by 12,7-100%, thrombin time decrease by 83,4-85%, and antithrombin III decreases by 15,3-21,7%), while in tilapias, acceleration of blood clotting by intrinsic and extrinsic pathways were recorded by the end of the experiment only in fishes with imitation of chronic stress (prothrombin time decrease by 76,8%, activated partial thromboplastin time decrease by 20,0%, and 2,3 multiplying soluble fibrin monomer complexes). Conclusions: It was concluded that the adaptive mechanisms of the tilapia (Oreochromis niloticus) organism allowed the clotting function to recover in most cases by the end of the experiment in all groups of fish, in contrast to carps (Cyprinus carpio).

Peculiarities of blood coagulation disorders in patients with COVID-19

To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19. We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes. Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

Splenomegaly development and disseminated intravascular coagulation syndrome in acute canine babesiosis

Disseminated intravascular coagulation (DIC) syndrome is the main defining process in the pathogenetic axis of complications in canine babesiosis. The involvement of the spleen with further irreversible changes in the organ largely determines the severity of the animal’s condition after spontaneous babesiosis. The work presented here aimed to determine the role of the DIC syndrome as a triggering factor for lesions of the spleen. Clinical and laboratory studies (haematological, biochemical, hemodynamic) have been carried out. Pathological studies of the removed spleen were carried out by histological methods using universal and specific staining. After suffering acute spontaneous babesiosis, the development of hypersplenism and splenomegaly was found in dogs. The diagnosis was confirmed haematologically by the detected cytopenia, normochromic type anaemia. An additional parameter was a significantly increased erythrocyte sedimentation rate. The biochemical profile indicated the development of bilirubinaemia due to the conjugated fraction, hyperfermentation of transaminases, hypoalbuminemia, which reflected the development of hepatitis and liver failure. Markers of DIC syndrome in laboratory studies are represented by reliable hypofibrinogenemia, increased level of fibrinogen/fibrin degradation products, including D-dimer, and soluble fibrin monomer complexes. The multidirectional indices of coagulation tests (activated partial thromboplastin and prothrombin time) made it possible to classify the stage of “consumption coagulopathy” of the DIC syndrome. The haemodynamic parameters of the sick dogs were characterized by a significant deficit in the circulating blood volume. Together with the indicators of the “consumption coagulopathy” stage of the DIC syndrome, the hemodynamic indexes indicate a moderate degree of shock stage II – the stable reversibility, but the magnitude of the circulating blood volume deficit determines the tendency towards shock irreversibility. Histological studies have established a significant proliferation of the stromal elements of the organ, the formation of specific complexes of vessels with sinuses, clogging with blood clots, and the organ's parenchyma dystrophy. Such changes characterize complete splenomegaly, which is based on the organo-pathology of the DIC syndrome. The deposition of “old” fibrin in the connective tissue structures of the spleen indicates that DIC syndrome continues throughout the entire period of hyperplastic changes in the organ. The presence of hyalinosis in blood vessel walls of the spleen parenchyma determines irreversible changes in them. Thus, DIC syndrome is the basis for splenomegaly development in dogs after acute spontaneous babesiosis. It is confirmed by laboratory blood tests and histologically by the presence of fibrin thrombi in the structures of the organ, which determine the organopathology of the syndrome. The information obtained serves to expand the concepts of the pathogenesis of blood protozoal disease, define the high risk of complications that can become fatal for the health and life of animals.

Hemodynamics and functional state of the contralateral kidney in the early postoperative period after surgical treatment of kidney cancer

AIM: To study the hemodynamics and functional state of the renal tissue of the contralateral kidney in the early postoperative period after surgical treatment of kidney cancer.
 MATERIALS AND METHODS: The prospective study included 58 patients with renal cell carcinoma, 36 (62.1%) of whom underwent radical nephrectomy, and 22 (37.9%) underwent partial nephrectomy. Tumor sizes ranged from 1.0 to 12.0 cm. All patients before surgery and in the early postoperative period underwent ultrasound examination of the structure and size of the kidneys, Doppler ultrasonography of the renal vessels, biomicroscopy of the bulbar conjunctiva, measured peripheral blood pressure, determined the glomerular filtration rate (GFR) and performed a coagulogram. The control group included 16 healthy adults.
 RESULTS: In 83.3% of patients after radical nephrectomy and in 13.6% of patients after partial nephrectomy a tendency towards an increase in blood pressure compared with the initial values was noted by the 2-4th day after the operation. By the 5th day after surgery, the volume of the only kidney remaining after radical nephrectomy increased by an average of 4% (from 126.1 1.4 to 131.2 2.1 cm3, p 0.05), while after partial nephrectomy has not changed reliably. After surgery, a decrease in GFR was detected in 34 (58.6%; p 0.05) patients, including after radical nephrectomy (n = 28) up to 73.4 8.2 ml / min / 1.73 m2, after partial nephrectomy (n = 6) up to 98.2 3.4 ml / min / 1.73 m2. Doppler ultrasonography of the vessels of a single kidney in patients after radical nephrectomy showed a moderate increase in linear blood flow, an increase in the resistance index in the main trunk of the renal artery, and a decrease in the pulsation index in the segmental and arc arteries. In patients after partial nephrectomy in the contralateral kidney these changes were not observed. When performing biomicroscopy of the bulbar conjunctiva in 83.3% of patients after radical nephrectomy and in 13.6% of patients after partial nephrectomy, changes in the microvasculature were revealed: narrowing of arterioles, expansion of venules, slowing of venular and capillary blood flow. Before the operation and in the early postoperative period, the content of fibrinogen and soluble fibrin-monomer complex in the blood of patients with renal cell carcinoma was significantly higher than in the control group.
 CONCLUSIONS: In patients with renal cell carcinoma, changes in the contralateral kidney in the early postoperative period after radical nephrectomy are significantly more pronounced than after partial nephrectomy, and are accompanied by changes in systemic and local hemodynamics and kidney function. The results of the study confirm the feasibility of performing organ-preserving surgeries in patients with renal cell carcinoma.

Two-stage fixation in the treatment of diabetic arthropathy of the ankle

Aim — to improve the results of treatment of diabetic anklearthropathies by using the final method of fixation by semi-rigid systems after arthrodesis and the use of extrafocal ring fixators (RF). Materials and methods. The authors presented own experience of treatment of 12 patients with diabeticankle osteoarthropathy. After arthrodesis and fixation with RF, the alternating osteosynthesis was performed with Scotchcast/Softcast bandages. The use of extrafocal RF of the needle-rod type in the first stage with low trauma wasadvantageous, however the time of fixation before the appearance of the fusion between the tibia and talus was significant, which led to a decrease in the rigidity of the fixation of the bone-needle system and development of inflammation at the exit of the spokes. This required the transition to other means of fixation, which would provide the possibility of functional use of the limb. The authors used Scotchcast/Softcast functional bandages, applied circularly, with stiffeners on the lateral surfaces, which allowed to carry out the supporting function of the limb. Interventions (arthrodesis of the ankle joint) were performed under multimodal analgesia. Vascular disorders required hematopoietic therapy (use of a tourniquet and administration of tranexamic acid solution) and bemiparin administrationfor microthrombosisprevention. Treatment of diabetic neuropathy and metabolic disorders was carried out by prescribing vitamin B and C, drugs Ca and vitamin D3, antioxidants. Results. The dynamics of the most examined indicators of the coagulation — anticoagulation system did not differ significantly (activated partial thromboplastic time, prothrombin time, international normalized ratio, platelet quantity). There was a tendency to shift the indicators to the recommended safe zone and even a significant decrease in the level of soluble fibrin monomer complexes (R2= 0.9494). Conclusions. The use of Scotchcast/Softcast immobilizing bandages in patients with diabetic arthropathy was safe after arthrodesis and RF fixation.This strategy allowed to restore limb capacity in the early stages of treatment, which improved the social adaptation of patients.

THROMBOELASTOGRAPHY IN ASSESSING THE HEMOSTATIC SYSTEM IN INTENSIVE CARE PATIENTS

The results of thromboelastography and standard coagulogram were analyzed in 35 patients aged from 18 to 86 who were treated in the resuscitation and intensive care unit. The majority of patients (34%) were hospitalized in the department with multisystem and concomitant injuries. The remaining patients were taken to the medical institution with different diagnoses (urolithiasis, liver cirrhosis, pancreatic lesion of various types, poisoning, peptic ulcer, sepsis). The data of coagulogram and thromboelastography at different stages of treatment were compared. In patients with the development of traumatic shock, the coagulogram parameters were changed to varying degrees depending on the stage of shock. At the first stage of shock, only an increase in soluble fibrin-monomer complexes by almost 2 times and a slight increase in fibrinogen dynamics were noted in the analysis. In a patient with stage 3 traumatic shock, the coagulogram parameters were within the normal range, but according to thromboelastography (EXTEM and FIBTEM tests), hypocoagulation due to the platelet link was noted. Only the coagulogram was evaluated in dynamics, hypocoagulation was noted in the indicators of internal and external hemostasis pathways: lengthening of the activated partial thromboplastin time, a decrease in the prothrombin index and an increase in the international normalized ratio, an increase in fibrinogen A and soluble fibrin-monomer complexes. In the group of male patients with closed craniocerebral trauma, an increase in soluble fibrin-monomer complexes in the coagulogram was always combined with changes in the FIBTEM test during thromboelastography. In most patients, no changes in the classical coagulogram tests immediately after the injury are noted. At this, thromboelastography makes it possible to make up for this deficiency at an earlier time, which indicates a high sensitivity of the method.

Вплив альбумінурії на стан плазмового гемостазу у хворих на гіпертонічну хворобу

В останні десятиріччя численні наукові роботи присвячено дослідженню клінічної та прогностичної значимості альбумінурії, методів її виявлення, а також лікувальних заходів, що направлені на боротьбу з даним патологічним станом. Метою роботи було встановити особливості змін плазмового гемостазу у хворих на гіпертонічну хворобу залежно від наявності альбумінурії. Матеріали і методи. Нами було обстежено 113 осіб: 14 практично здорових (1-ша група, контроль), 41 хворий на гіпертонічну хворобу (ГХ) II стадії із супутньою альбумінурією (2-га група), 58 хворих на ГХ II стадії без супутньої альбумінурії (3-тя група). Проводили лабораторні дослідження: активований частковий тромбопластиновий час, протромбіновий індекс, тромбіновий час, фібриноген, розчинні фібрин-мономерні комплекси (РФМК), час ХІІа-залежного фібринолізу, антитромбін ІІІ, протеїн С. Результати. Був виявлений підвищений вміст РФМК, який у 3-й групі хворих на 135 %, а в 2-й групі хворих — на 247 % перевищував конт­рольні значення. При цьому у хворих з альбумінурією він був набагато вищим навіть за показник у групі хворих на ГХ без альбумінурії — на 48 %. Час XII-а залежного фібринолізу як у 2-й, так і в 3-й групі був набагато більшим за норму. Виражені зміни відбувались з боку системи природних антикоагулянтів, що були статистично значущими по відношенню до групи контролю лише у групі хворих з альбумінурією, а у групі хворих без альбумінурії вони суттєво не відрізнялись від групи контролю. Висновки. У хворих на гіпертонічну хворобу незалежно від вираженості альбумінурії спостерігалось значне пригнічення фібринолітичної активності крові та активації останніх ланок згортання крові — фібриноутворення. Наявність альбумінурії асоціювалась з більш суттєвою активацією фібриноутворення та поєднувалась із пригніченням власної антикоагулянтної активності крові, про що свідчило зменшення вмісту антитромбіну III та протеїну С.

Asymptomatic Venous Thromboembolism After Hepatobiliary-Pancreatic Surgery: Early Detection Using D-dimer and Soluble Fibrin Monomer Complex Levels.

AimThe aim was to investigate the usefulness of a preemptive management strategy that includes monitoring serum D‐dimer (DD) and soluble fibrin monomer complex (SFMC) levels for early detection and treatment of venous thromboembolism (VTE) after hepatobiliary–pancreatic (HBP) surgery.MethodsOverall, 678 patients who underwent HBP surgery between January 2010 and March 2020 were enrolled. Patients with increased postoperative serum DD or SFMC levels underwent contrast‐enhanced computed tomography, and those with VTE received anticoagulant agents. The VTE risk factors were investigated using multivariable analysis. Postoperative changes in DD and SFMC levels were verified, and their ability to identify VTE was evaluated using receiver operating characteristic (ROC) analysis.ResultsVTE developed in 83 patients (12.2%), and no symptomatic VTE or death due to VTE was observed. Multivariable analysis identified female sex (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.41–3.60; P < .001) and surgery duration of ≥401 min (OR 2.07; 95% CI 1.27–3.35; P < .001) as independent risk factors for VTE. Maximum serum DD and SFMC levels in patients who developed VTE were significantly higher than those in patients without VTE (DD, 15.1 vs 8.9 μg/mL, P < .001; SFMC, 18.0 vs 10.2 μg/mL, P < .001, respectively). Both DD (n = 678) and the combination of DD and SFMC levels (n = 230) showed a good ability to detect VTE (area under the ROC curve, 0.804 and 0.761, respectively).ConclusionOur preemptive strategy of monitoring serum DD and SFMC levels enables early detection and treatment intervention of VTE after HBP surgery.

A system for predicting the development of coronary heart disease in miners with anthracosilicosis

Introduction. Among underground miners, the pathology of the cardiovascular system is much more common than among workers on the surface, which indicates the negative role of the impact of harmful production factors. There is evidence of a high prevalence of traditional risk factors for the development of coronary heart disease among miners with dust pathology of the lungs. Preventive measures for coronary heart disease exist for the timely detection and elimination of risk factors. In this regard, it is relevant to optimize methods for predicting the risk of developing coronary heart disease in coal mine workers. The study aims to develop a system for predicting the probability of developing coronary heart disease in miners with anthracosilicosis based on determining the most significant risk factors. Materials and methods. The experts studied the frequency of coronary heart disease and its risk factors in 139 employees of the primary professions of coal mines. The scientists performed daily ECG monitoring, bicycle ergometry according to the Rose questionnaire. They also studied the indicators of lipid metabolism, hemostasis, the level of homocysteine, C-reactive protein, glycemia, the presence of excess body weight, constitutional and morphological types according to Rice-Eysenck and Tanner. The experts developed a predictive system using the Bayes method. We calculated a predictive coefficient for each factor. Scientists determined the probability of coronary heart disease by the value of the sum of prognostic coefficients. Results. Workers aged 45 years and older have the highest risk of developing coronary heart disease. The experience of working in harmful working conditions for 20 years or more, the presence of arterial hypertension, metabolic syndrome, respiratory failure, andromorphic constitutional-morphological type according to the Tanner index, as well as the presence of hyperhomocysteinemia, hyperfibrinogenemia, increased levels of soluble fibrin-monomer complexes and C-reactive protein - all these are the risks of developing coronary heart disease in miners with anthracosilicosis. Conclusions. The developed system of personalized prediction of the probability of developing coronary heart disease in miners with anthracosilicosis allows us to identify a group of high-risk workers for timely treatment and preventive measures for them.

Activity of coagulation processes with comorbid hypertension and coronary heart disease

Purpose – determine the characteristics of changes of procoagulant, anticoagulant and fibrinolytic links of the hemostatic system in patients with hypertension in combination with coronary heart disease.&#x0D; Materials and methods. 127 people were examined - 14 healthy (control), 61 patients with stage II hypertension with concomitant coronary heart disease (group 2), 52 hypertensive patients with stage III with concomitant coronary heart disease (group 3). There were evaluated indicators of hemostasis system: thrombin time, activated partial thromboplastin time, prothrombin index, soluble fibrin monomer complex, fibrinogen, protein C, antithrombin III of, and the time of XII-dependent fibrinolysis.&#x0D; Results. Patients on both study groups SFMC content significantly higher than the control group. SFMC content in patients with stage II hypertension with concomitant coronary heart disease exceed normative value of 3 times, and in the group of hypertensive patients with stage III with with concomitant coronary heart disease of 3.65 times. The content of fibrinogen in the third group of patients exceeded the indicators of the control group by 27.6%, the difference was significant (p&lt;0,001). Also valid was the difference between the two comparable groups (p&lt;0,001). The content of protein C in hypertensive patients stage III was lower than the control values at 28,7% (p&lt;0,001). The difference between comparable groups also were significantly (p&lt;0,001). At the same time, and XII-dependent fibrinolysis in patients with stage II hypertension in combination with coronary heart disease was 3.54 times longer than the standard values (p&lt;0,001), and the combination of hypertension III stage with CAD - 4.7 times longer than the norm (p&lt; 0.001).&#x0D; Conclusions. Patients with hypertension stage II and III with concomitant coronary heart disease characterized by increased blood clotting activity in the background suppression of the anticoagulant and fibrinolytic components of hemostasis. The largest contribution to the formation of thrombophilic changes in patients of both treatment groups belongs to inhibition of fibrinolysis, which is more pronounced when hypertension stage III combined with coronary heart disease.

A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia.

IntroductionA neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in tissue factor—a thromboplastin. This prothrombotic aspect likely explains how a respiratory virus whose malign effects should be confined to the oropharynx, bronchi and lungs, can cause a panoply of extra‐pulmonary organ disorders. Elevated ferritin levels in ICU Covid 19 patients, and elevated acute phase proteins suggest immune overreaction. Elevated d‐dimers implicate clotting as well. This evidence links hyperactive innate immunity (macrophage lung infiltrates) with the elevated levels of oligomeric fibrin present in the bloodstream of these patients.MethodsAn in‐house assay measuring oligomeric (soluble) fibrin (also referred to as soluble fibrin monomer complexes or SFMC) in whole blood, previously developed for monitoring incipient disseminated intravascular coagulation (DIC) during liver transplantation, was made available to COVID ICU attendings. Since SFMC constitutes the input to intravascular fibrin clots and d‐dimer reflects fibrin clot dissolution, it was thought that the two tests, run in tandem along with assays of immune activation, might clarify the frequency and possibly the cause of DIC in patients with severe COVID‐19 pneumonia.ResultsClassical DIC with intravascular clotting and thrombocytopenia was documented only rarely. However, early in the pandemic shortly after the assay was made available, it identified three patients undergoing acute defibrination. In each patient virtually all of the body's fibrinogen was transformed into SFMC over 3–4 days and deposited somewhere in the vasculature without any gross clots being detected.ConclusionsThree COVID‐19 patients with evidence of a hyperactive immune response (elevated ferritin and acute phase proteins) defibrinated while blood levels of SFMC were being monitored. SFMC levels that were five times higher than normal appeared in the circulation during the defibrination process. SFMC at these levels may precipitate as showers of microclots, damaging heart, kidney, brain, and so forth.

Характеристика функціонального стану гемостазу у жінок після пангістеректомії І типу залежно від індексу маси тіла

Neoplastic processes are a pathogenic trigger for the development of thrombotic complications, including deep vein thrombosis and pulmonary artery thromboembolism. Post-operative thrombosis is one of the leading mortality causes of oncological patients due to its asymptomatic course, and therefore due to the late diagnosis and treatment. Purpose — to estimate the coagulation system condition in women after the type I hysterectomy depending on their body mass index. Materials and methods. The study of hemostasis parameters of 50 patients with the uterus and uterine appendages oncological diseases depending on the body mass index was carried out. The results were processed by the method of variation statistics, which became the basis for their generalization. Calculations of the parametric Student's t-test and methods of nonparametric statistics (Mann–Whitney test) were used. Differences between comparable parameters were found statistically significant at p&lt;0.05. Results. The analysis of hemostasis parameters in oncological patients has revealed a twice higher concentration of fibrinogen and soluble fibrin monomer complexes in comparison to the control group. All three groups were characterized by hyperthrombocytopenia. The surgery provoked further activation of I, II, and III phases of coagulation on the background of negative thrombodynamics caused by intraoperative blood loss. In women with I and II obesity grade no statistically significant differences in coagulogram were observed, whereas in patients with III obesity grade the thrombotic potential was significantly more aggressive. Conclusions. Oncological diseases of the female reproductive system are associated with the impairment of coagulation status: lower activated partial thromboplastin, hyperfibrinogenemia, and increased prothrombin index. The surgery was a significant trigger of the increase of hemostatic potential with the progressive increase of the markers of I, II, and III coagulation phases. III obesity grade is an independent risk factor for thrombotic complications. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: oncogenesis, deep vein thrombosis, clotting, obesity, complications.

Preoperative Lower Extremity Motor Weakness Affects Deep Vein Thrombosis During the Perioperative Period of Lumbar Surgery.

Prospective cohort study. The aim of this study was to assess preoperative factors in the development/exacerbation of deep vein thrombosis (DVT) in lumbar surgery and selectively perform lower-extremity venous ultrasonography (US) in patients at risk of perioperative deep vein thrombosis (DVT). DVT is often present before lumbar surgery and also can develop or is exacerbated postoperatively. An elevated d-dimer level is predictive of DVT but not in all patients or during every operative period. The level of the thrombogenic marker soluble fibrin monomer complex (SFMC) peaks early postoperatively. The study enrolled 698 patients (396 males; 12- 91 years [346 patients aged ≥70 years] at surgery) undergoing surgery for lumbar degenerative diseases. Patients with d-dimer levels ≥0.5 μg/mL or with a lower-extremity manual muscle test (MMT) < grade 3 underwent preoperative US. All preoperative DVT-positive patients and patients with SFMC levels ≥20 μg/mL on postoperative day 1 (POD1) underwent US. Patients with pre- and postoperative femoral-vein DVT underwent screening for pulmonary embolism (PE). There were 251 patients with preoperative d-dimer levels ≥ 0.5 μg/mL, including 226 with MMT ≥ grade 3, 38 (16.8%) of whom were DVT-positive on US. In 48 patients with MMT <grade 3, DVT was detected in 16 of 25 patients with d-dimer levels ≥ 0.5 μg/mL (64.0%) and 10 of 23 with d-dimer levels <0.5 μg/mL (43.5%). Postoperatively, 26 of 64 preoperative DVT-positive patients (40.6%) had postoperative exacerbation of DVT; PE occurred in three. Among 100 of 634 preoperative DVT-negative patients, US revealed new DVT in 14 (2.2%) and PE in one. Preoperative DVT and new postoperative DVT were significantly more common in patients aged ≥70 years; postoperative DVT exacerbation was significantly more common in patients aged <70 years. A significantly higher proportion of patients with motor weakness had preoperative DVTs and postoperative exacerbated or new DVTs. Preoperative DVT screening by US is advisable for patients with elevated d-dimer levels, lower extremities with MMT < grade 3, or DVT positivity. Postoperative US is advisable for patients with elevated SFMC levels on POD1.Level of Evidence: 3.

The Usefulness of the Combination of D-Dimer and Soluble Fibrin Monomer Complex for Diagnosis of Venous Thromboembolism in Psychiatric Practice: A Prospective Study.

PurposeD-dimer has the advantage of excluding venous thromboembolism (VTE) due to its high sensitivity but is disadvantageous for diagnosing VTE due to its low specificity. A method to increase the usefulness of D-dimer in the diagnosis of VTE is warranted. This study aimed to investigate the usefulness of the combination of D-dimer and soluble fibrin monomer complex (SFMC), which has been suggested as a new candidate marker for VTE, in VTE diagnosis.Patients and MethodsThis prospective study in 109 subjects was performed at a psychiatric department between August 1, 2017 and December 31, 2019. Subjects’ levels of D-dimer and SFMC were measured simultaneously. Plasma levels of D-dimer and SFMC were measured using NANOPIA® D-dimer and NANOPIA® SF. Subjects with positive D-dimer (≥1.0 µg/mL) results underwent contrast computed tomography for confirmation of VTE within 12 hours of D-dimer measurement. A receiver operating characteristic curve analysis was performed to examine the usefulness of SFMC for the diagnosis of VTE.ResultsOnly 109 of the 783 subjects without symptoms suggestive of VTE participated in the study. Out of 41 subjects with positive D-dimer results, 17 subjects were diagnosed with VTE. A receiver operating characteristic curve analysis was performed to determine cutoff values. The area under the curves was 0.848 for SFMC (p<0.001, 95% CI 0.722 to 0.974), and the optimal cutoff value was 10.0 µg/mL (sensitivity 58.8%, specificity 100%, positive predictive value 100%, negative predictive value 77.4%).ConclusionSFMC was useful for diagnosing VTE in the psychiatric patients with positive D-dimer results.

Risk factors for coronary heart disease in miners with anthracosilicosis

Introduction. There are data on the effects of dust on the respiratory system and the cardiovascular system. The main measures for preventing diseases of the circulatory system aimed to identify and eliminate risk factors. However, the prevalence of risk factors for coronary heart disease among coal mine workers with anthracosilicosis has not been sufficiently studied, determining the study's relevance. The study aimed to learn the frequency of risk factors for coronary heart disease in coal industry workers with anthracosilicosis. Materials and methods. We examined 269 miners working in conditions of dustiness exceeding the maximum permissible concentration by ten or more times: 139 miners with a previously established diagnosis of anthracosilicosis and 130 miners of the control group without dust pathology of the lungs. All of them underwent a comprehensive clinical, instrumental, and laboratory examination of the respiratory and cardiovascular systems to detect anthracosilicosis and coronary heart disease, as well as to assess its risk factors. Results. In miners with anthracosilicosis, coronary heart disease was 3.5 times more common (30.94%) than in the control group (8.46%). We have identified a high incidence of coronary heart disease in the age group of 45 and more years and with the experience of working in dust conditions of 20 and more years. In miners with anthracosilicosis combined with coronary heart disease, arterial hypertension was 1.6 times more common (58.14%) than without concomitant coronary heart disease - 35.42%. Miners with a combination of anthracosilicosis and coronary heart disease were three times more likely (20.93%) than those without coronary heart disease (6.25%) to have a metabolic syndrome. According to the Tanner index, significant risk factors for coronary heart disease were the presence of an andromorphic constitutional-morphological type and the formation of a complication of anthracosilicosis - respiratory failure. The evaluation of biochemical blood tests showed that the most significant markers of coronary heart disease risk were hyperhomocysteinemia, increased levels of C-reactive protein, fibrinogen, and soluble fibrin-monomer complexes. Conclusions. We found that the most significant risk of developing coronary heart disease in miners is 45 years and older. There are also other risk factors: work experience in harmful working conditions of 20 years or more; the presence of arterial hypertension; metabolic syndrome; andromorphic constitutional-morphological type according to the Tanner index. Risk factors are respiratory failure, hyperhomocysteinemia, hyperfibrinogenemia, increased soluble fibrin-monomer complexes, and C - reactive protein. It is necessary to consider all risks in developing programs of medical and preventive measures for employees of the coal industry.

Plasma Hemostasis in Patients with Essential Hypertension and Non-alcoholic Fatty Liver Disease Under Conditions of Hypercholesterolemia and Concomitant Statin Therapy

In the modern scientific world, it has been proven that non-alcoholic fatty liver disease (NAFLD) is a marker of the risk of cardiovascular (CV) events, and therefore, attention and control of risk factors for CV diseases is important. Considering the prevalence of atherogenic dyslipidemias and their proven effect on the development of thrombotic CV complications in patients with NAFLD, it is important to understand the role of hemostatic blood activity. The objective: To increase the efficiency of early diagnosis of thrombophilic changes in the blood in patients with essential hypertension (HT) combined with non-alcoholic fatty liver disease by determining the state of plasma hemostasis in conditions of hypercholesterolemia and concomitant statin therapy. Materials and methods. 152 patients were examined. Patient groups: I – 46 patients with stage II hypertension, II – 54 patients with NAFLD without hypertension, group III – 52 patients with stage II hypertension with concomitant NAFLD. Results. The growth of prothrombogenic activity of the blood among all groups of patients, however, with HT II stage, combined with NAFLD, the most significant effect was carried out precisely on the final stages of coagulation. An increase in the level of fibrinogen was observed in patients with grade II hypertension. by 29,3 % (p&lt;0,01) and with a combination of HT and NAFLD by 39,7 % (p&lt;0,001). The levels of soluble fibrin-monomeric complexes in all groups were significantly higher than the control values: in patients with hypertension. – 4,1 times (p&lt;0,001), with NAFLD – 2,8 times (p&lt;0,001), in the NAFLD group with hypertension – 4,5 times (p&lt;0,001). Antithrombin III (AT III) was reduced by 12,3 % (p&lt;0,01) relative to the control only in patients with hypertension. On the other hand, the fibrinolytic potential was reduced among all examined groups. Determination of the effect of lipid-lowering therapy revealed an acceleration of prothrombin time (PTT) by 19.2 % (p&lt;0,01) in patients with NAFLD without statin treatment. In the general cohort, statin use increased the activity of AT III by 10,7 % (p&lt;0,01), but in the NAFLD group, this difference was more significant – by 14,3 % (p&lt;0,001). In patients with comorbid course of HT and NAFLD with cholesterolemia level &lt;5 mmol/L, we observed an increase in PTT by 32,5 % (p&lt;0,05), INR by 25,4 % (p&lt;0,05) and thrombin time by 23,2 % (p&lt;0,05) during statin therapy. On the other hand, in the subgroup with hypercholesterolemia, statins increased the activity of the anticoagulant link of hemostasis – the level of ATIII increased by 3,1 % (p&lt;0,05). Conclusions. Depletion of the fibrinolytic potential against the background of activation of the coagulant hemostasis link is observed in patients with hypertension combined with NAFLD. In the case of concomitant hypercholesterolemia, the procoagulant activity of the blood increases, however, against the background of treatment with statins, there is a decrease in the coagulation potential of the blood and an increase in the activity of the anticoagulant link of hemostasis.

Blood Coagulation Changes With or Without Direct Oral Anticoagulant Therapy Following Transcatheter Aortic Valve Implantation

Thromboembolic events remain clinically unresolved after transcatheter aortic valve implantation (TAVI). The use of direct oral anticoagulant (DOAC) to reduce thrombosis associated with TAVI remains controversial. This study aimed at investigating the periprocedural change in blood coagulation and thrombolysis parameters in 199 patients undergoing transfemoral TAVI. Prothrombin activation fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), soluble fibrin monomer complex (SFMC), and fibrin/fibrinogen degradation product (FDP) levels were measured before and 1 hour after TAVI and 1, 2, and 7 days postoperatively. Of the 199 patients, 49 were treated with DOAC (apixaban in 32, edoxaban in 10, and rivaroxaban in 7). The F1 + 2 and TAT levels immediately increased 1 hour after TAVI and then gradually decreased in both groups. The SFMC level also significantly increased with a peak on day 1. The FDP level gradually increased, peaking on day 2. The values of F1 + 2, TAT, SFMC, and FDP in patients who used DOAC were significantly lower than those who did not use DOAC at 1 hour after TAVI in F1 + 2 (600 [452 to 765] vs 1055 [812 to 1340] pmol/L; p < 0.001), TAT (21.4 [16.2 to 37.0] vs 38.7 [26.4 to 58.7] μg/mL; p < 0.001) and on day 1 in SFMC (18.2 [9.4 to 57.9] vs 113.4 [70.9 to 157.3] μg/mL; p < 0.001) and day 2 in FDP (6.0 [4.7 to 10.0] vs 12.6 [8.2 to 17.4] μg/mL; p < 0.001). Ischemic stroke within 30 days after TAVI occurred in 3 patients (1.5%), who were not treated with DOAC. Coagulation cascade activation was observed after TAVI. DOAC could reduce transient hypercoagulation following TAVI.