Activation Of Hemostasis Research Articles

Establishing Expectancy Values for Fibrin Monomer in Uncomplicated Pregnancy.

Background During pregnancy, a physiological increase of molecular activation markers (MAM) of hemostasis such as prothrombin fragments 1 + 2, thrombin-antithrombin complex, and D-dimers (DD) occurs. Therefore, monitoring MAM levels during pregnancy to evaluate the risk of venous thromboembolism (VTE) may be unreliable; nevertheless, DD analysis in pregnancy is widely performed. In contrast to DD, fibrin monomer (FM) levels have been reported to remain stable during pregnancy. Objectives The main aim of this study was to define the expected range for FM levels in pregnant outpatients. In addition, we examined the impact of the individual VTE risk, as calculated by the pregnancy risk score of the Royal College of Obstetricians and Gynaecologists (RCOG), as well as that of antithrombotic treatment on FM levels. Methods A total of 342 pregnant women seen at our hemostasis unit were included throughout 350 pregnancies in 899 samples. Results Low-risk thrombophilia, but not the RCOG score itself, was found to influence all MAM levels, whereas antithrombotic treatment had only an impact on DD. For FM, a reference range could be calculated irrespective of the pregnancy term, in contrast to other MAMs, which fluctuated throughout pregnancy. Conclusions Our findings suggest a stronger impact of inherited thrombophilia on hemostasis activity during pregnancy as compared with acquired or other predisposing thrombophilic risk factors. FM levels showed a marginal increase during pregnancy in contrast to other MAM and remain a potential candidate to improve the laboratory assessment of VTE risk during pregnancy. Further prospective studies in pregnant patients with suspicion of VTE are needed.

Human platelet concentrates treated with microbicidal 405 nm light retain hemostasis activity

Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light. Apheresis PC samples collected from each screened human donor (n = 22) were used for testing of PCs and platelet poor plasma (PPP). Both PCs and PPPs were treated for 5 h with 405 nm light to achieve a previously established microbicidal light dose of 270 J/cm2. Activated partial thromboplastin time and prothrombin time-based potency assays using a coagulation analyzer and hemostatic capacity via Thromboelastography were analyzed. Thromboelastography analysis of the light-treated PCs and plasma present in the PCs showed little difference between the treated and untreated samples. Further, plasma present in the PCs during the light treatment demonstrated a better stability in potency assays for several coagulation factors compared to the plasma alone prepared from PCs first and subjected to the light treatment separately. Overall, PCs stored in plasma treated with 405 nm violet-blue light retain activity for hemostasis.

Dependence of blood coagulation activity on temperature in cows <i>in vitro</i>

The paper presents the results of a study on how temperature affects the coagulation and anticoagulation processes in the hemostasis system of cows. The purpose of this work was to study the coagulation parameters of the blood of Ayrshire cows with hypo-, normo- and hyperthermia "in vitro", as well as to evaluate the possibility of using a coagulometer to characterize the activity of hemostasis and use hemostatic reactions in cattle as models for human medicine. The study was carried out in the Vologda region. The following parameters of the coagulation profile were analyzed: thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and antithrombin III (AT-III) activity. Results showed that at 43 °C hypercoagulation of the blood occurred, which in clotting methods manifests itself as an acceleration of TT by 61 % (27 sec), PT by 29 % (10 sec), a prolongation of APTT by 38 % (25 sec) and a decrease in Antithrombin III activity by 51 % (5 sec) compared with normothermia. At 18 °C, hypocoagulation was detected, accompanied by an elongation of all indicators characterizing the rate of clot formation: TT by 10 % (5 sec), PT by 61 % (55 sec), APTT by 83 % (289 sec). Fibrinogen activity decreased by 82 % (106 sec), and AT-III activity increased by 85 % (56 sec) compared to normothermy. The correlation between hemostasis parameters and the temperature factor can be characterized as negative moderate (APTT), noticeable (TV, fibrinogen) and close (PT, AT-III). Using a medical coagulometer caused reaction rates to differ significantly from those occurring at the body temperature of these animals when studying the coagulation mechanisms of cows. This does not allow to recommend this device for an adequate assessment of hemostatic reactions in cattle.

Venous Thrombosis in Airborne Viral Infections: Is Coronavirus Disease 2019 now Any Different from Influenza?

One of the hallmarks of coronavirus disease 2019 (COVID-19), particularly in complicated cases (i.e., requiring hospitalization or intensive care support), is persistent hemostasis activation, which may be associated with a vast array of thrombotic episodes involving both the arterial and venous systems. The renewed emphasis on the relationship between viral infections and venous thrombosis paves the way for determining whether a more common and often underestimated infection disease, such as influenza, may also be associated with a significant burden of venous thrombotic episodes, and how this eventual thrombotic risk compares to that seen in COVID-19, both in the past and with newer variants. Our review of studies comparing the burden of venous thromboembolism (VTE) in patients with COVID-19 or influenza revealed that the thrombotic risk appears to be significantly higher in patients with COVID-19 but remains certainly not meaningless in those with influenza, particularly in subjects infected by highly virulent strains (i.e., H1N1), in those who develop pneumonia and require intensive care support. In these specific clinical settings, the adoption of tailored thromboprophylaxis may be indicated though more studies are compellingly needed on this matter. As COVID-19 variants emerge, there is a possibility that the VTE burden of COVID-19 will decrease, and progress to that of other respiratory viruses.

Features of the systemic influence of cervical cancer on peripheral blood and hemostasis according to the tumor histological subtype

Aim. To identify the features of the systemic effect on hematopoiesis and the blood coagulation system of different histological subtypes of cervical cancer (CC).Materials and methods. A single-center retrospective cohort study of 428 patients (61 patients with high grade squamous intraepithelial lesion (carcinoma in situ) and 367 patients with CC) examined from 1997 to 2022 in the Polyclinic of P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia. The age of patients was from 18 to 90 years (median age – 42 [34; 51] years). Patients were divided into 4 groups: group 1 – patients with high grade squamous intraepithelial lesion and 3 groups depending on tumor’s histological subtype (squamous cell, glandular squamous cell, adenocarcinoma). Demographic and clinical data were analyzed including laboratory tests (general blood count, biochemical blood test and iron metabolism and coagulograms (total 32 variables)) compared to clinical and surgical stages of CC.Results. High grade squamous intraepithelial lesion does not have a systemic effect on the parameters of general, biochemical blood tests and hemostasis (p >0.05). On the other hand, statistically significant changes were found in the parameters of routine laboratory blood tests, which correlate with the results of microinvasive analysis of CC, thus revealing the systemic effect of a malignant tumor: at p ≤0.001 for thrombin time, total protein, alkaline phosphatase levels; at p ≤0.05 for alanine aminotransferase, aspartate aminotransferase, C-reactive protein, serum iron and urea levels. Among patients with CC, statistically significant (p<0.001) correlations were obtained between hematological, hemostasiological and biochemical blood parameters. Of statistical significance, the presence of the glandular component in the tumor increases the systemic effect of CC on blood parameters, hemostasis, markers of inflammation and iron metabolism: leukocytosis and maximum erythrocyte sedimentation rate values compared to CC, high fibrinogen and the level of soluble fibrin-monomer complexes which increased activation of coagulation hemostasis along the common coagulation pathway (thrombin time) (p<0.001). It leads to an increase in the risk of venous thromboembolic complications in this category of patients.Conclusion. The identified changes in blood parameters made it possible to reveal the unique biological characteristics of each histological subtype of CC, including biochemical ones, which will help in developing an improved diagnosis of CC depending on the histological subtype and stage of the disease, along with developing preventive measures and treatment methods adapted to each specific case.

Dependence of coagulation activity of chicken blood IN VITRO on temperature

The paper presents the results of examine the relationship between blood plasma incubation temperature and the hemostasis parameters in chickens. The purpose of this research was to study of the blood coagulation parameters in chickens during hypo-, normo- and hyperthermia in vitro. In addition, to assess the possibility of using a coagulometer to identify hemostasis activity and the use of hemostatic reactions in chickens as models for human medicine. The Vologda region was where the study was conducted. The coagulogram was examined for the following parameters: thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen activity, and antithrombin III activity (AT-III). It was found that at 46° C activation of blood clotting occurs, manifested as an acceleration of the TT by 29% (13 seconds), PT by 72% (111 seconds), and decrease in the antithrombin III activity by 6% (1.5 seconds) compared to normothermia. The parameters of secondary hemostasis also responded to hypothermia (18 °C) with hypercoagulation. It was an acceleration of PT of 81% (125 sec), an increase in fibrinogen activity by 77% (84 sec) and a decrease in AT-III activity by 55% (14 sec), with the exception of thrombin time, which was extended by 70% (104 seconds). There were no significant changes in the APTT at different temperatures. The correlation-regression and one-factor analysis of variance revealed a significant correlation between the temperature and the TT and the fibrinogen activity, where the coefficients of determination for which were 71% and 39%, respectively. Plasma hemostasis activity measured on a coagulometer (at 37 °C) showed no significant differences from those measured at 43 °C, except for prothrombin time, which was 71.51 seconds (47%) less than that measured at 43 °C.

Risk of Thrombosis and Mechanisms of Activation of Hemostasis in Divers after Diving

Risk of Thrombosis and Mechanisms of Activation of Hemostasis in Divers after Diving

Autoimmune Heparin-Induced Thrombocytopenia.

Autoimmune thrombocytopenia (aHIT) is a severe subtype of heparin-induced thrombocytopenia (HIT) with atypical clinical features caused by highly pathological IgG antibodies ("aHIT antibodies") that activate platelets even in the absence of heparin. The clinical features of aHIT include: the onset or worsening of thrombocytopenia despite stopping heparin ("delayed-onset HIT"), thrombocytopenia persistence despite stopping heparin ("persisting" or "refractory HIT"), or triggered by small amounts of heparin (heparin "flush" HIT), most cases of fondaparinux-induced HIT, and patients with unusually severe HIT (e.g., multi-site or microvascular thrombosis, overt disseminated intravascular coagulation [DIC]). Special treatment approaches are required. For example, unlike classic HIT, heparin cessation does not result in de-escalation of antibody-induced hemostasis activation, and thus high-dose intravenous immunoglobulin (IVIG) may be indicated to interrupt aHIT-induced platelet activation; therapeutic plasma exchange may be required if high-dose IVIG is ineffective. Also, aHIT patients are at risk for treatment failure with (activated partial thromboplastin time [APTT]-adjusted) direct thrombin inhibitor (DTI) therapy (argatroban, bivalirudin), either because of APTT confounding (where aHIT-associated DIC and resulting APTT prolongation lead to systematic underdosing/interruption of DTI therapy) or because DTI inhibits thrombin-induced protein C activation. Most HIT laboratories do not test for aHIT antibodies, contributing to aHIT under-recognition.

Risk of Thrombosis and Mechanisms of Activation of Hemostasis in Divers after Diving

The risks of decompression sickness and its complications in professional divers and amateur divers with various methods of diving in real and simulated conditions are considered. The pathogenesis of disorders of the plasma and vascular hemostasis system under the influence of environmental factors on the body during various types of dives is discussed. Generalization of the research results showed that the mechanisms of activation of thrombosis under this influence are complex and are caused by microbubble-mediated platelet activation as well as by development of endothelial dysfunction, oxidative and psychophysiological stress. The study of hemostasis parameters in professional and amateur divers can be one of the main methods of assessing the risk of its development. The considered means of preventing thrombosis during diving and decompression, according to the results of the works included in the review, are quite effective.

Circulating D-dimer level may predict tumor burden in chronic hepatitis C related hepatocellular carcinoma

Introduction: Coagulation and fibrinolysis activation has been implicated in angiogenesis, tumor cell invasion, tumor progression and metastatic spread. D-dimer is a biomarker that globally indicates the activation of hemostasis and fibrinolysis. Aim: To study the correlation of circulating D-dimer level with the tumor grade in HCV related HCC. Methods: HCC was diagnosed by non- invasive method in cirrhotic patients according to EASL criteria using contrast enhanced abdominal CT and or MRI. After metastatic work up, HCC grade was described as grade one if it was within Milan criteria (one nodule <5cm or up to 3 nodules; the largest is <3cm without vascular invasion or extra- hepatic involvement); grade two if it was beyond Milan criteria but non –metastatic & grade three if it was metastatic (vascular invasion, lymph node metastasis, distant metastasis). BCLC staging depending on HCC burden, Child -Turcotte-Pugh (CTP) class and ECOG performance status (PST), was done for all studied cases. Chromic HCV was diagnosed by 4th generation ELIZA for HCV antibody and confirmed by quantitative PCR for HCV RNA. Circulating D dimer level, serum AFP level, liver biochemical tests, serum creatinine & complete blood count were measured for all studied cases. Patients with history of previous treatment for HCC; recent benign thrombo-embolic disorder or renal impairment were excluded. Results: Fifty chronic HCV related HCC cases; 43 males and 7 females with age 62.2±7.4 years were enrolled. Circulating D-dimer level was significantly higher in HCC grade 2 and 3 than HCC grade 1 [(400-800) versus (0-400 ng/ml), p=0.001] & in BCLC stage D than BCLC stage C HCC [(400-800) versus (0-700 ng/ml), p=0.021].There was significant positive correlation between circulating D-dimer level and HCC size and HCC grade (r =0.35, p = 0.012, r =0.33, p = 0.016 respectively). There was also significant positive correlation between circulating D-dimer level and both serum AFP level (r =0.45, p=0.001) and ECOG performance status (r =0.4, p = 0.002). Serum level of circulating D-dimer at cut off level ≥300 ng/ml can predict HCC grade beyond Milan criteria (G2& 3) with PPV of 77.1%, NPV of 73.3%, AUC= 0.8 and p <0.0005.Also, serum AFP level at cut off ≥394.5 can predict HCC grades beyond Milan criteria with PPV of 89.3%, NPV of 72.7%, AUC= 0.81 and P<0.0005. Conclusion: In HCV related HCC, circulating D-dimer level was positively correlated with HCC grade and largest tumor size with higher level in HCC grades 2&3 as well as BCLC stage D. Cut off level of circulating D-dimer level of ≥300 ng/ml can predict HCC grades beyond Milan criteria.

RATIONALE FOR PRESCRIBING ANTICOAGULANT THERAPY IN THE COMPLEX TREATMENT OF PURULENT-NECROTIC COMPLICATIONS OF DIABETIC FOOT SYNDROME

Abstract. This article is based on the study of hemostasis indicators in 25 patients with diabetic foot syndrome. Diabetic foot syndrome (DFS) develops against the background of diabetic neuropathy, micro- and macroaniopathy, osteoarthropathy, which lead to frequent traumatization of the soft tissues of the foot, infection with the subsequent development of purulent-necrotic processes on the foot, and in the course of progression leads to high limb amputations. According to the international federation, which deals with the problem of diabetes mellitus (DM), the 21st century is considered a pandemic of DM. It should be noted that the number of patients with diabetes is increasing every year. Patients with diabetes are characterized by an atherothrombotic state caused by multiple disorders in the hemostasis system. Hemostatic disorders in patients with diabetes are complex and include activation of natural mechanisms of the coagulation system, inhibition of fibrinolytic activity, and various platelet dysfunctions.
 The purpose of the study is to substantiate the appointment of anticoagulation therapy in patients with SDS.
 Materials and methods. On the basis of KNP KMKL No. 6 in Kyiv in 2023, for a period of 6 months, 69 patients with SDS were treated. The state of indicators of the coagulation link of the hemostasis system in 49 people was studied. At the same time, 26 patients had purulent-necrotic complications of the neuroischemic form of SDS, 23 people were healthy (comparison group). The patients were divided according to the article and age, according to the duration of diabetes mellitus, and according to the stages according to Wagner. The following indicators were determined for patients: prothrombin index (PTI), plasma recalcification time, fibrinogen, B-naphthol test, ethanol test, Willebrand factor, endothelin-1, coagulation factor (VIII), fibronectin.
 The results of the study and their discussion: Based on the study, 61.5 % of patients with SDS are of working age. Of them, 57.7 % are men, 42.3 % are women. The largest number of patients with SDS is observed in the group of patients who have had diabetes for more than 10 years - 57.7 %, and the largest number of patients with stage III-IV according to Wagner - 88.5 %. In patients with diabetes with neuroischemic form of SDS, the PTI level is increased by 28.8 % and the prothrombin time is shortened by 21 %, which indicates an increase in the activity of external blood clotting mechanisms. An increase in fibrinogen by 29.7 % indicates an increase in the activity of coagulation hemostasis. Willebrand factor increased by 34.5 %, coagulation factor (VIII) increased by 20.3 %, fibronectin increased by 83.01 %, which indicates an increase in aggregation and procoagulant processes, which in turn increases thrombus formation.
 Conclusion. Thus, with diabetic foot syndrome, hypercoagulation is observed, which leads to an increase in the level of thrombus formation, which justifies the appointment of anticoagulant therapy in the complex treatment of diabetic foot syndrome.

Hemostasiological Aspects of PCI: Periprocedural Changes in the Activity of the Platelet Link of Hemocoagulation on the Background of Prior Double Antiplatelet Therapy in Patients with Chronic Coronary Syndrome

The aim. To analyze changes in the activity of the platelet link of hemocoagulation in patients with chronic coronary syndrome before and after percutaneous coronary intervention (PCI) against the background of prior antiplatelet therapy.
 Materials and methods. We examined 67 patients (mean age 65.2±8.6 years) who were undergoing inpatient treatment at the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. Patients with different regimens of antiplatelet therapy were compared before and after PCI. At the time of hospitalization, patients were receiving both monotherapy and dual antiplatelet therapy (those with a history of myocardial infarction up to 12 months) in standard doses. The control group consisted of 25 people of similar age (62.7±6.5 years). The activity of platelet hemostasis was evaluated by the turbidimetric method and the light transmission fluctuation method. Statistical processing was carried out using the MedStat v.5.2 and Statistica 8.0 software.
 Results. Before PCI, dual antiplatelet therapy using aspirin and ticagrelor suppressed the activity of platelet hemostasis, compared to dual antiplatelet therapy with acetylsalicylic acid and clopidogrel. Patients receiving monotherapy did not achieve the desired effect. After PCI, the group of patients who took the combination of aspirin and ticagrelor responded better to the therapy than those who received aspirin and clopidogrel.
 Conclusions. The use of dual antiplatelet therapy with acetylsalicylic acid and ticagrelor reduced both spontaneous and induced aggregation.

PECAM-1/Thrombus Ratio Correlates with Blood Loss during Off-Pump Coronary Artery Bypass Grafting (OPCAB) Surgery: A Preliminary Study.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is considered an antiplatelet molecule. Previously, we introduced a new parameter called the PECAM-1/thrombus ratio, which indicates the proportion of PECAM-1 in the thrombus and provides a precise description of human platelet activity (in vitro). The aim of this study was to determine whether the PECAM-1/thrombus ratio could serve as a predictive factor for bleeding events during off-pump coronary artery bypass grafting (OPCAB). To achieve this, we collected blood samples from 20 patients scheduled to undergo OPCAB surgery. We assessed the PECAM-1/thrombus ratio by evaluating thrombus formation on collagen fibers under flow conditions. Subsequently, we compared the ability of the PECAM-1/thrombus ratio in predicting bleeding risk with other methods that evaluate hemostasis activity. These methods included assessing platelet P-selectin secretion, platelet exposure of phosphatidylserine, plasma coagulation and fibrinolysis system activity, and thrombus formation using the T-TAS assay. Our findings revealed a positive correlation between the PECAM-1/thrombus ratio and the amount of blood component units transfused (BCUT) during the OPCAB surgery. Furthermore, BCUT did not show any significant correlation with other measured hemostasis parameters. This preliminary study suggests that the PECAM-1/thrombus ratio might be a good predictor of bleeding risk during the OPCAB procedure.

Study of the relationship between hemostasis and vascular endothelium in hypoxic lesions of the nervous system in newborns

The study of the statement of the hemostatic system and vascular endothelium was made in newborns with hypoxic lesions of the nervous system. Some indicators of hemostasis (PTT, APTT, TT and fibrinogen) were determined in cord blood, as well as endothelial dysfunction marker Endothelin-1. In newborns who underwent a chronic hypoxia, a statistically significant increase of the fibrinogen level and endothelin-1 were revealed in the umbilical cord blood. During hypoxic lesions of the nervous system in newborns the vascular endothelium primarily reacts, causing activation of hemostasis and cerebral blood flow disorders.

Advanced in vitro hemocompatibility assessment of biomaterials using a new flow incubation system

Physiologically relevant in vitro hemocompatibility assessment of biomaterials remains challenging. We present a new setup that enables standardized whole blood incubation of biomedical materials under flow. A blood volume of 2 mL is recirculated over test surfaces in a custom-made parallel plate incubation system to determine the activation of hemostasis and inflammation. Controlled physiological shear rates between 125 s−1 and 1250 s−1 and minimized contact to air are combined with a natural-like pumping process. A unique feature of this setup allows tracing adhesion of blood cells to test surfaces microscopically in situ. Validation testing was performed in comparison to previously applied whole blood incubation methodologies. Experiments with the newly developed setup showed that even small obstacles to blood flow activate blood (independent of materials-induced blood activation levels); that adhesion of blood cells to biomaterials equilibrates within 5 to 10 min; that high shear rates (1250 compared to 375 s−1) induce platelet activation; and that hemolysis, platelet factor 4 (PF4) release and platelet loss - but not thrombin formation – depend on shear rate (within the range investigated, 125 to 1250 s−1).

Podoplanin and CLEC-2 levels in patients with COVID-19

BackgroundPodoplanin (PDPN gene) and CLEC-2 are involved in inflammatory hemostasis and have also been related with the pathogenesis of thrombosis. Emerging evidence also suggests that podoplanin can exert protective effects in sepsis and acute lung injury. In the lungs, podoplanin is coexpressed with angiotensin-converting enzyme 2, which is the main entry receptor for SARS-CoV-2. ObjectivesTo explore the role of podoplanin and CLEC-2 in COVID-19. MethodsCirculating levels of podoplanin and CLEC-2 were measured in 30 consecutive patients with COVID-19 admitted due to hypoxia and in 30 age- and sex-matched healthy individuals. Podoplanin expression in lungs from patients who died of COVID-19 was obtained from 2 independent public databases of single-cell RNA sequencing, from which data from control lungs were also available. ResultsCirculating podoplanin levels were lower in patients with COVID-19, whereas no difference was observed in CLEC-2 levels. Podoplanin levels were significantly inversely correlated with markers of coagulation, fibrinolysis, and innate immunity. Single-cell RNA sequencing data confirmed that PDPN is coexpressed with angiotensin-converting enzyme 2 in pneumocytes and showed that PDPN expression is lower in this cell compartment in the lungs of patients with COVID-19. ConclusionCirculating levels of podoplanin are lower in patients with COVID-19, and the magnitude of this reduction is correlated with hemostasis activation. We also demonstrate the downregulation of PDPN at the transcription level in pneumocytes. Together, our exploratory study questions whether an acquired podoplanin deficiency could be involved in the pathogenesis of acute lung injury in COVID-19 and warrants additional studies to confirm and refine these findings.

Bradykinin release following trauma and hemorrhagic shock causes pulmonary alveolar leak in a rodent model.

Hemorrhage accounts for 40% of the preventable death following severe injury. Activation of systemic coagulation produces bradykinin (BK), which may cause leak from the plasma to the extravascular space and to the tissues, which is part of the complex pathophysiology of trauma-induced end-organ injury. We hypothesize that BK, released during activation of coagulation in severe injury, induces pulmonary alveolar leak. Isolated neutrophils (PMNs) were pretreated with a specific BK receptor B2 antagonist HOE-140/icatibant and BK priming of the PMN oxidase was completed. Rats underwent tissue injury/hemorrhagic shock (TI/HS), TI/icatibant/HS, and controls (no injury). Evans blue dye was instilled, and the percentage leak from the plasma to the lung was calculated from the bronchoalveolar lavage fluid (BALF). CINC-1 and total protein were measured in the BALF, and myeloperoxidase was quantified in lung tissue. The BK receptor B2 antagonist HOE140/icatibant inhibited (85.0 ± 5.3%) BK priming of the PMN oxidase ( p < 0.05). The TI/HS model caused activation of coagulation by increasing plasma thrombin-antithrombin complexes ( p < 0.05). Versus controls, the TI/HS rats had significant pulmonary alveolar leak: 1.46 ± 0.21% versus 0.36 ± 0.10% ( p = 0.001) and increased total protein and CINC-1 in the BALF ( p < 0.05). Icatibant given after the TI significantly inhibited lung leak and the increase in CINC-1 in the BALF from TI/icatibant/HS rats versus TI/HS ( p < 0.002 and p < 0.05) but not the total protein. There was no PMN sequestration in the lungs. Conclusions: This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release. This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release. Original Article, Basic Science.

Thrombotic or Thromboembolic Events in COVID-19: A Literature Review

Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a novel virus infection, was first detected in China in 2019 and has quickly spread as a pandemic leading to a high mortality rate and unprecedented challenges for healthcare systems. Although the SARS-CoV-2 clinical spectrum is different, acute failure of respiratory function and coagulopathy as a common manifestation can be observed in cases with severe coronavirus disease 2019 (COVID-19). Methods: This literature review was conducted based on standard guidelines to evaluate related-to-title information about thrombotic or thromboembolic events in COVID-19. Keywords were combined and included as “thrombotic event”, “thromboembolic events”, “diagnosis”, “management”, “SARS-CoV-2”, “COVID-19”, and “literature review”. Results: Lung tissue is a serious target of the COVID-19 virus leading to acute respiratory distress syndrome related to a thromboinflammatory condition. The storm of cytokines, pulmonary tropism, and thromboinflammation are bases of tissue damage leading to acute failure of the respiratory system and extended infection, which can lead to different organ failure and death. The thrombogenicity of this condition has been shown by the high prevalence rate of thromboembolic events observed in SARS-CoV-2 cases treated with anticoagulation. Enhanced D-dimers, as a biomarker reflecting the activation of fibrinolysis and hemostasis, and thrombocytopenia have a relationship with a higher mortality rate in COVID-19 cases. Conclusions: Based on the finding, the inflammation phase of COVID-19 can induce thromboinflammation and lead to thromboembolic events.

Hemostasis parameters as prognostic biomarkers in gynecological cancer patients

Hypercoagulation is a typical condition for cancer patients. In addition, various arms of the hemostasis system become involved in tumor growth, invasion, metastasis, neoangiogenesis as well as immunoevasion. The magnitude of activated hemostasis is driven by tumor phenotype. Parameters characterizing coagulation, intensity of fibrinolysis processes, platelet aggregation and activation as well as endothelial activation mirror magnitude of hemostasis activation in oncological process, but may also be considered as candidate markers of tumor progression and predictors of oncological diseases outcome. This review summarizes the study data assessing a value of predictive hemostasis biomarkers for overall survival and response to therapy in oncogynecology and mammology. The most promising biomarkers have been identified and used in the future for risk stratification as well as personalized patient management.

CORRELATION OF PLASMA D-DIMER LEVEL IN FEMALE BREAST CARCINOMA PATIENTS WITH CLINICAL STAGES AND HISTOPATHOLOGICAL PARAMETERS

Background: Breast cancer is one of the leading disease among females in the world. There is a correlation between cancer and hypercoagulation. In a cancer state, there is an increase in the level of cross-linked brin degradation product (d-dimer) which indicates systemic activation of brinolysis and hemostasis. So, there is a relation between an increase in d-dimer value and breast carcinoma.Objective:This study was done in an attempt to evaluate the role of D-dimer in patients with carcinoma breast, in predicting lymph node metastasis in carcinoma patients and to look for the relationship of these markers with histopathologic parameters Method: A prospective observational descriptive study was done in Dr. S N medical college attached hospitals (department of surgery) from Jan 2022 to Jan 2023. Forty-three breast carcinoma patients were included in the study after core needle biopsy conrmation. Plasma d-dimer levels compared with (tumor size, stage, grade, lymphovascular invasion, and lymph node involvement). Data collected and analysed. Results: Forty three patients were studied with age from 21 to 76yrs(mean age-51).left side tumor was more common 52%. D-dimer level was increasing with enlarged tumor size, high stage, high grade, lymphovascular invasion, and lymph node involvement. All are statstacally signicant.(p value: &lt;0.001) Conclusions: Plasma D-dimer level is important preoperative marker with which we can predict the advance stage breast cancer. It is also an important marker of clinical stage progression, lymphovascular invasion, and metastasis . Pre-operative plasma D-dimer level is a safe, cost-effective, and convenient method for the prediction of advanced-stage breast cancer