scholarly journals Accelerated Spatial Fibrin Growth and Impaired Contraction of Blood Clots in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (24) ◽  
pp. 9434
Author(s):  
Alina D. Peshkova ◽  
Tatiana A. Evdokimova ◽  
Timur B. Sibgatullin ◽  
Fazoil I. Ataullakhanov ◽  
Rustem I. Litvinov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Binding Capacity ◽  
Blood Clot ◽  
Clinical Manifestations ◽  
Fibrin Clot ◽  
Control Group ◽  
Plasma Clot ◽  
Blood Clots ◽  
Clot Contraction ◽  
Hemostatic Disorders

Rheumatoid arthritis (RA) is an autoimmune disease associated with thrombotic complications. To elucidate pathogenic mechanisms, hemostatic disorders in RA were correlated with other laboratory and clinical manifestations. Hemostasis was assessed using relatively new complementary tests, the spatial growth of a plasma clot (Thrombodynamics assay), and contraction of whole blood clots. Platelet functionality was assessed with flow cytometry that quantified the expression of P-selectin and the fibrinogen-binding capacity of platelets before and after activation with a thrombin receptor-activating peptide. Parameters of fibrin clot growth and the kinetics of contraction of blood clots were significantly altered in patients with RA compared to the control group. In Thrombodynamics measurements, an increase in the clot growth rate, size, and optical density of plasma clots altogether indicated chronic hypercoagulability. The rate and extent of blood clot contraction in patients with RA was significantly reduced and associated with platelet dysfunction revealed by an impaired response to activation. Changes in the parameters of clot growth and contraction correlated with the laboratory signs of systemic inflammation, including hyperfibrinogenemia. These results confirm the pathogenic role of hemostatic disorders in RA and support the validity of fibrin clot growth and the blood clot contraction assay as indicators of a (pro)thrombotic state.

CHANGES IN THE PARAMETERS OF THROMBODYNAMICS AND BLOOD CLOT CONTRACTION IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 58 (3) ◽  
pp. 294-303
Author(s):  
A. D. Peshkova ◽  
T. A. Evdokimova ◽  
T. B. Sibgatullin ◽  
F. I. Ataullakhanov ◽  
R. I. Litvinov
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Clot ◽  
Clinical Manifestations ◽  
Control Group ◽  
Healthy Individuals ◽  
Plasma Clot ◽  
Autoimmune Pathology ◽  
Clot Contraction ◽  
Hemostatic Disorders

Autoimmune diseases, including rheumatoid arthritis (RA), are risk factors for thrombotic events. Understanding the pathogenetic role of hemostatic changes in RA can assist in developing measures for prevention, prognosis, early diagnosis, and treatment of immune thromboses. Objective: to investigate the state of platelet and plasma hemostasis in patients with RA, as compared to other laboratory parameters and clinical manifestations of the disease. Subjects and methods. Hemostasis was investigated using two relatively new laboratory tests: thrombodynamics and kinetics of blood clot contraction (BCC). Examinations were made in 60 patients with RA and in 50 apparently healthy individuals of the control group. Results and discussion. In patients with RA, the parameters of thrombodynamics and BCC were found to be significantly different from the normal values. According to thrombodynamics, there was an increase in plasma clot growth rate, size, and density, which indicates chronic hypercoagulation. The rate and completeness of BCC were substantially reduced due to platelet dysfunction in patients with RA compared to healthy individuals. The changes in the parameters of thrombodynamics and BCC correlated with the laboratory signs of systemic inflammation and depended on the radiographic stage of the disease. Conclusion. The results of this investigation confirm that hemostatic disorders are present in RA and indicate the informative value of thrombodynamics and BCC tests as indicators of a pre-thrombotic state, including autoimmune pathology.

scholarly journals Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 354
Author(s):  
Rustem I. Litvinov ◽  
Alina D. Peshkova ◽  
Giang Le Minh ◽  
Nail N. Khaertdinov ◽  
Natalia G. Evtugina ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Activation ◽  
Rat Model ◽  
Binding Capacity ◽  
Blood Clot ◽  
Fibrinogen Binding ◽  
Blood Clots ◽  
Clot Contraction ◽  
Dose Dependent

Hyperhomocysteinemia (HHcy) is associated with thrombosis, but the mechanistic links between them are not understood. We studied effects of homocysteine (Hcy) on clot contraction in vitro and in a rat model of HHcy. Incubation of blood with exogenous Hcy for 1 min enhanced clot contraction, while 15-min incubation led to a dose-dependent suppression of contraction. These effects were likely due to direct Hcy-induced platelet activation followed by exhaustion, as revealed by an increase in fibrinogen-binding capacity and P-selectin expression determined by flow cytometry. In the blood of rats with HHcy, clot contraction was enhanced at moderately elevated Hcy levels (10–50 μM), while at higher Hcy levels (>50 μM), the onset of clot contraction was delayed. HHcy was associated with thrombocytosis combined with a reduced erythrocyte count and hypofibrinogenemia. These data suggest that in HHcy, platelets get activated directly and indirectly, leading to enhanced clot contraction that is facilitated by the reduced content and resilience of fibrin and erythrocytes in the clot. The excessive platelet activation can lead to exhaustion and impaired contractility, which makes clots larger and more obstructive. In conclusion, HHcy modulates blood clot contraction, which may comprise an underappreciated pro- or antithrombotic mechanism.

scholarly journals TITANIUM NANOPARTICLES CONJUGATED WITH STREPTOKINASE AS A MODIFIED THROMBOLYTIC AGENT

2020 ◽  
pp. 18-25
Author(s):  
HAYDER H. ABED ◽  
ESTABRAQ AR. ALWASITI ◽  
AMIR T. TAWFEEQ
Keyword(s):  
Thrombolytic Agent ◽  
Blood Clot ◽  
Control Group ◽  
Thrombolytic Activity ◽  
Protein Assay ◽  
Blood Clots ◽  
Ft Ir ◽  
Titanium Nanoparticles ◽  
D Dimer

Objective: Blood clots are the main cause of death worldwide by stroke and myocardial infarction. Streptokinase a thrombolytic agent that is used in the treatment of circulatory disorders. Methods: Titanium Nanoparticles was supplied from Changsha Santech Co. Its characterized were studied using (FT-IR, XRD, AFM, FE-SEM). Streptokinase at concentration 0.1 mg/ml was conjugated with Titanium nanoparticles using PH equal to 5.2 with continuous stirring. Formation of Streptokinase loading Titanium nanoparticles confirmed using FT-IR, Ninhydrine’s test and Bradford protein assay. Physicochemical Properties were studied in vitro. Thrombolytic activity in vitro was determined using d–dimer indicator and weight of blood clot after treatment as indicators of thrombolytic activity. Results: Titanium nanoparticles show particle size at range 31 nm. The thrombolytic activity of streptokinase loading Titanium nanoparticles shows significant value in d-dimer and weight of blood clot compared with the control group and non-significant compared with an equivalent amount of streptokinase alone. Conclusion: Titanium nanoparticles conjugated with streptokinase show high thrombolytic activity against blood clots in vitro.

scholarly journals Impaired contraction of blood clots precedes and predicts postoperative venous thromboembolism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Natalia G. Evtugina ◽  
Alina D. Peshkova ◽  
Arseniy A. Pichugin ◽  
John W. Weisel ◽  
Rustem I. Litvinov
Keyword(s):  
Brain Tumors ◽  
Blood Clot ◽  
Surgical Interventions ◽  
Hematologic Tests ◽  
Vein Thrombosis ◽  
Blood Clots ◽  
Postoperative Thrombosis ◽  
Clot Contraction ◽  
Deep Vein ◽  
Contraction Assay

Abstract Deep vein thrombosis (DVT) is a common but unpredictable complication of surgical interventions. To reveal an association between the blood clot contraction (retraction) and the incidence of postoperative venous thrombosis, 78 patients with brain tumors that were operated on were studied, of which 23 (29%) were diagnosed with postoperative DVT. A clot contraction assay, along with other hemostatic and hematologic tests, was performed 1–3 days before the surgery and on the 1st day and 5–7th days after the surgery. On the 1st postoperative day, clot contraction was significantly suppressed in patients who subsequently developed DVT, compared to the patients without DVT. Importantly, this difference was observed at least 5 days before DVT had developed. The weakening of contraction on the 1st postoperative day was more pronounced in the DVT patients with malignant versus benign brain tumors, atherosclerosis, hypertension, as well as in patients receiving steroids before and during the operation. These results indicate that impaired clot contraction in the postoperative period is associated with imminent DVT, suggesting that it is a prothrombotic risk factor and promotional mechanism. The clot contraction assay has a predictive value in assessing the threat of postoperative thrombosis in patients with benign and malignant brain tumors.

Premorbid Hemostasis in Women with a History of Pregnancy Loss

2019 ◽  
Vol 119 (12) ◽  
pp. 1994-2004 ◽  
Author(s):  
Alina D. Peshkova ◽  
Svetlana I. Safiullina ◽  
Natalia G. Evtugina ◽  
Yelena S. Baras ◽  
Fazoil I. Ataullakhanov ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Blood Clot ◽  
Significant Inhibition ◽  
Obstetric Complications ◽  
In Vitro Assays ◽  
History Of ◽  
Clot Contraction ◽  
Hemostatic Disorders ◽  
In Pregnancy

Abstract Background Congenital and acquired hemostatic disorders are among the pathogenic factors of pregnancy loss. Studying mechanistic relations between impaired hemostasis and fetal losses is important for the prognosis and prophylaxis of obstetric complications. Objective This article aims to establish latent hemostatic disorders in nonpregnant women as an important premorbid risk factor of pregnancy loss. Methods and Results Hemostasis was characterized using two relatively new in vitro assays, namely thrombodynamics (spatial clot growth) and kinetics of blood clot contraction, which together reflect the hemostatic or thrombotic potential. In addition, platelet functionality was assessed using flow cytometry. Our study included 50 women with a history of pregnancy loss and 30 parous women without previous obstetric complications. In patients with pregnancy loss, hypercoagulability was observed along with significant impairment of blood clot contraction associated with chronic platelet activation and dysfunction. Both hypercoagulability and defective clot contraction were significantly more pronounced in patients with a history of three or more miscarriages compared with patients with a history of one or two miscarriages. In addition, a significant inhibition of clot contraction was found in patients with miscarriage occurring after 10 weeks of gestation compared with those who lost a fetus earlier in pregnancy. Conclusion These results indicate that chronic hypercoagulability and impaired clot contraction constitute a premorbid status in patients with pregnancy loss. The data confirm a significant pathogenic role of hemostatic disorders in pregnancy loss and suggest the predictive value of thrombodynamics and blood clot contraction assays in evaluating the risk of pregnancy loss.

scholarly journals Pathobiochemical Mechanisms Relating Iron Homeostasis to Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis

Folia Medica ◽  
2016 ◽  
Vol 58 (4) ◽  
pp. 257-263 ◽  
Author(s):  
Katya I. Stefanova ◽  
Ginka T. Delcheva ◽  
Ana I. Maneva ◽  
Anastas Z. Batalov ◽  
Mariela G. Geneva-Popova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
Binding Capacity ◽  
Autoimmune Disorders ◽  
Inflammatory Activity ◽  
Control Group ◽  
Reactive Protein ◽  
Das 28 ◽  
Two Parameters

Abstract Aim: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). Materials and methods: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies, and DAS 28. Results: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. Conclusion: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative in evaluating the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.

scholarly journals Comparison of clinical manifestations of rheumatoid arthritis in patients with moderate or high disease activity depending on the presence or absence of symptoms of neuropathic pain

2021 ◽  
Vol 15 (6) ◽  
pp. 13-18
Author(s):  
E. Yu. Polishchuk ◽  
E. S. Filatova ◽  
A. E. Karateev ◽  
V. N. Amirdzhanova ◽  
V. A. Nesterenko
Keyword(s):  
Rheumatoid Arthritis ◽  
Neuropathic Pain ◽  
Disease Activity ◽  
Pain Intensity ◽  
Clinical Manifestations ◽  
High Disease Activity ◽  
Control Group ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

Objective: to study the effect of neuropathic pain symptoms (SNP) on the clinical manifestations of rheumatoid arthritis (RA) in patients with moderate or high disease activity.Patients and methods. The 1st (main) group included 58 RA patients (84.5% of women, age 53.0±11.9 years), in whom SNP were identified using the DN4 (≥4) and PainDETECT (≥13) questionnaires. The 2nd (control) group included 43 patients with RA (79.1% women, age 48.8±14.4 years) who did not have SNP (DN4 ≤4 and PainDETECT ≤13). All patients received disease-modifying antirheumatic drugs (mainly methotrexate and leflunomide), 20% – biologic disease-modifying antirheumatic drugs. We compared groups 1 and 2 for RA activity (DAS28, CDAI, SDAI), pain intensity on a visual analogue scale (VAS, 0–100 mm), functional impairment (HAQ), patient global assessment (PGA, VAS), number of painful and swollen joints, quality of life (EQ-5D), signs of anxiety and depression (HADS), CRP level.Results and discussion. The RA activity in patients of the 1st and 2nd groups did not differ statistically significantly. Patients of the 1st group showed significantly higher indicators of the severity of pain, PGA and anxiety than patients of the control group: 71.0±12.5 and 54.7±17.5 mm, respectively (p<0.001); 61.0±13.1 and 53.7±15.3 mm (p=0.045); 62.1 and 28.6% (HADS ≥7; p<0.001), respectively.Conclusion. SNP are associated with higher rates of pain intensity, PGA, and anxiety in RA patients with moderate to high disease activity.

scholarly journals The Results of Fetal Chondrocytes Transplantation in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 3 ◽  
Author(s):  
Natalya Krivoruchko ◽  
Saltanat Tuganbekova ◽  
Gulnar Rakhimbekova ◽  
Karlygash Kuzembaeva ◽  
Lina Zaripova
Keyword(s):  
Rheumatoid Arthritis ◽  
Morphological Changes ◽  
Control Cell ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Human Embryos ◽  
Control Group ◽  
X Ray ◽  
Donor Cells

Introduction. Nowadays anti-inflammatory and immunosuppressive therapy has significantly improved the quality of life and prognosis of rheumatoid arthritis (RA). Nevertheless, there are still many patients with progressive rheumatoid inflammation, resulting in the destruction of joints. Cell therapy seems like a promising direction in rheumatology. The aim of our research was to evaluate the efficacy of fetal chondrocyte transplantation in patients with RA.Methods. We examined 60 patients with rheumatoid arthritis (I - III stages) between 20 and 63 years of age. They were divided into 2 groups: the first group underwent the fetal chondrocytes transplantation (n = 40), and the second was a control group who got conservative therapy (n = 20). Donor cells were taken from the chondrogenic layer of the humerus or femur heads and hip condyles of human embryos in gestation for 17-20 weeks. A suspension of fetal chondrocytes injected into affected areas of the articular surfaces under X-ray control. Cell viability was determined before the injection. Efficacy of the therapy was assessed by clinical, instrumental, and laboratory tests. This clinical trial was allowed by The Ministry of Public Health and Ethics Committee. All of our patients gave informed consent for the fetal chondrocytes transplantation.Results. Evaluation of the clinical manifestations of RA in the first group of patients showed 3.7 times decrease in pain and 1.6 times relief of synovitis. Complete reduction of contracture was observed in 82% of patients in the first group. Morphometric changes in X-ray demonstrated inhibition of the destruction in articular cartilage and surfaces of bones after transplantation of fetal chondrocytes. The dynamics of morphological changes in synovium showed 2.5 times reduction of the inflammatory reaction. Transplantation of fetal chondrocytes led to a significant reduction in ESR, CRP, fibrinogen , γ-globulin after a period of 12 months (p < 0.03). Furthermore, patients in the second group had 2.7 times higher risk of ankylosis compared to the first group. We did not observe any complications of fetal chondrocytes transplantation.Conclusions. Application of fetal chondrocytes therapy had the desired clinical effect, which was confirmed by reduction of the RA activity and decrease of cartilage and bone destruction. 

scholarly journals Clinical Manifestations of Periodontal Tissue Diseases in Patients with Rheumatoid Arthritis Who Live in Anthropogenically Loaded Areas

2020 ◽  
Vol 27 (3) ◽  
pp. E2020310
Author(s):  
Khristina Kovalyshyn ◽  
Mykola Rozhko
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Manifestations ◽  
Environmentally Friendly ◽  
Severe Form ◽  
Control Group ◽  
Periodontal Tissues ◽  
Group I ◽  
Periodontal Index ◽  
Somatic Diseases ◽  
Degree Of Severity

The objective of the study is to clinically assess the condition of periodontal tissues in patients with rheumatoid arthritis, living in anthropogenically loaded and environmentally friendly areas and in people with generalized periodontitis without concomitant somatic diseases. Materials and methods. There were examined 137 patients, including 82 patients with generalized periodontitis of the I degree (subgroups A) and the II degree (subgroups B) with rheumatoid arthritis, living in anthropogenically loaded areas (group I), environmentally friendly areas (group II) and without concomitant somatic diseases living in environmentally friendly areas (group III). Control group – included 18 healthy people. Periodontal tissues were evaluated according to the indices: Greene-Vermillion, PMA, periodontal index offered by Russel and the depth of periodontal pockets.  Results. Women (80%) dominated in each group, patients with generalized periodontitis of the II degree of severity dominated, too.  The highest depth of periodontal pockets was 5.02±0.11 mm in the IB subgroup and differed significantly from this figure in the IIB subgroup 1.07-fold (pIB-IIB<0.05) and from that in the IIIB subgroup 1.2-fold (pIB-IIIB<0.001). The value of the Greene-Vermilion index in patients with GP of the I degree of development in all subgroups A corresponded to “unsatisfactory”. In patients with GP of the II degree of development, the state of hygiene corresponded to “bad” in subgroups IB, IIB and was 3.04±0.11 points (pIB-IIB˂0.01, pIB-IIIB˂0.001, pIB-K˂0.001); 2,63 ± 0.07 points (pIIB-IB˂0.01, pIIB-IIIB˂0.001, pIIB-K˂0.001), in ІІІB – “unsatisfactory”. According to the indicators of the PMA index in patients with GP of the I degree of severity, we’ve found the average severity degree of gingivitis (within the range of 43.25±2.02 – 48.06±1.46%) and severe degree of gingivitis in patients with the GP of the II degree >50 %. The highest indicator of periodontal index was found in the IB subgroup – 6.16±0.10 points (pIB-IIB˂0.01, pIB-IIIB˂0.001, pIB-K˂0.001), which indicated a severe form of periodontitis. Conclusion. Most often, GP in patients with RA was diagnosed in women, most of whom were patients with GP of the II degree (most in group I – 69.04%). The highest depth of periodontal pockets was 5.02±0.11 mm in the IB subgroup. The performed clinical and index assessment of periodontal tissues in patients of three groups indicates a more severe course of GP of the I and II degree in patients with rheumatoid arthritis living in anthropogenically loaded areas (IA, IB subgroups).

Effects of Platelets and Erythrocytes on the Dynamic Size and Mechanical Properties of Blood Clots during Contraction

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4225-4225
Author(s):  
Valerie Tutwiler ◽  
Rustem I. Litvinov ◽  
Tatiana Lebedeva ◽  
Fazoil I. Ataullakhanov ◽  
Douglas B. Cines ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Viscoelastic Properties ◽  
Blood Clot ◽  
Final Size ◽  
Fibrin Network ◽  
Blood Clots ◽  
Platelet Concentration ◽  
Clot Contraction ◽  
Contractile Forces ◽  
Kinetics Of

Abstract Clot contraction is a final step of blood clotting and plays a key role in hemostasis and restoring blood flow past obstructive thrombi. The volume shrinkage of clots is driven by the contractile forces generated by activated platelets and propagated by the platelet-attached viscoelastic fibrin fibers throughout the entire clot. We have recently shown that blood clot contraction results in the formation of compressed. tightly packed, polyhedral erythrocytes (polyhedrocytes) and in the redistribution of platelets and fibrin to the surface of the contracted clot as a result of the complex interplay between platelets, fibrin, and erythrocytes. This study further investigates the role of these major blood cells in the dynamic mechanical (or viscoelastic) properties of the clot and the kinetics of clot contraction. Platelet and erythrocyte levels were varied through the use of partially reconstituted blood. Samples of platelet-containing plasma with or without added erythrocytes were recalcified and activated with thrombin. The viscoelastic properties and the force of contraction of the resultant clot were determined using high precision rheology. The kinetics of contraction was analyzed using a Thromboimager (HemaCore, Moscow, Russia), which allows continuous tracking and quantitative characterization of dynamic clot size by sensing changes in the light scattering of the clot over time. As predicted, the rate and degree of clot contraction depended linearly on the platelet count over a broad range (R2=0.9881). Increased platelet concentration of greater than 500 k/μl resulted in a more than 30% increase (p<0.001) in the percentage of clot contraction at 30 minutes when compared to the lowest platelet concentration (<75 k/μl). There was a significant increase in the rate and a ~15% increase (p<0.001) in the percentage of clot contraction seen in samples with 250-300k/μl, however, and no difference in samples with 125-150k/μl when compared to the lowest platelet concentration. It was observed that increasing the hematocrit level also affected the degree of contraction with a 30% decrease (p<0.001) in the percentage of contraction seen as the erythrocyte level was increased to hematocrit >40% when compared to <10% hematocrit. There was a 10-15% decrease in the percentage of contraction seen at intermediate hematocrit levels (p<0.05). In addition to decreasing the degree of contraction, changing the cellular composition also affected the rate of contraction. Increasing the concentration of either erythrocytes or platelets resulted in a relative increase in the viscous (or plastic) properties when compared to elastic (or stiffness) properties of the clot (p<0.01), showing a complex dependence of the viscoelastic behavior of the contracting clot as a result of the addition of cells. The presence of erythrocytes resulted in a 63% increase (p<0.05) in the contractile forces that were generated by the platelet-fibrin network when compared to platelets alone. We interpret these results as a profound effect of erythrocytes on the course of clot contraction and on the final size and mechanical properties of contracted blood clots. These results reveal that the concentration of cellular components critically affects the ability of the platelet-fibrin network on the outside of the clot to generate forces needed to reduce the clot size and to compact the erythrocytes, resulting in the formation of a stiff, dense hemostatic plug with low permeability. Disclosures Ataullakhanov: HemaCore LLC: Employment, Membership on an entity's Board of Directors or advisory committees.

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