Blood loss and coagulation profile in pregnant and non-pregnant queens undergoing elective ovariohysterectomy

Objectives The aims of this study were to determine if there is increased risk of intraoperative bleeding in pregnant cats undergoing elective ovariohysterectomy (OHE), and to compare coagulation in queens in various stages of estrus and pregnancy subjected to elective OHE using a whole-blood viscoelastic assay. Methods Intraoperative blood loss was compared between non-pregnant and pregnant cats undergoing elective OHE. Viscoelastic evaluations of whole blood drawn pre- and postoperatively were performed using a point-of-care device measuring clot time (CT), clot formation time (CFT), alpha angle, maximum clot formation (MCF), amplitude at 10 and 20 mins (A10 and A20, respectively), and lysis index at 30 and 45 mins after MCF (LI30 and LI45, respectively). Results One hundred and ninety-three cats underwent OHE by a ventral midline approach. Median blood loss was greater for pregnant cats (2.0 ml, range <0.5–13 ml) than non-pregnant cats (<0.5 ml, range <0.5–15 ml; P <0.0001). Preoperatively, pregnant cats had a shorter median CFT (165 s vs 190.5 s), increased median A10 (31 from 25.5 VCM units) and A20 (38 from 35 VCM units), and a lower median LI45 (99% from 100%) than non-pregnant cats. Postoperatively, A10 and A20 increased, and LI30 and LI45 decreased in both non-pregnant and pregnant queens. In pregnant queens, mean CT also increased postoperatively. Conclusions and relevance Pregnant cats were relatively hypercoagulable and had an increased rate of clot lysis than non-pregnant cats. Intraoperative blood loss was increased in pregnant vs non-pregnant cats, but no clinically relevant bleeding conditions occurred.

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FC 015LACK OF PLASMINOGEN RELATES TO A HYPERCOAGULABLE STATE IN MICE WITH EXPERIMENTAL NEPHROTIC SYNDROME

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab138.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Mengyun Xiao ◽

Stefanie Hammer ◽

Wissam A Khalel ◽

Lisann Pelzl ◽

Bernhard N Bohnert ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Alpha Angle ◽

Formation Time ◽

Clot Formation ◽

Hypercoagulable State ◽

Clot Lysis ◽

Activity Measurement ◽

Clotting Time ◽

Plasminogen Deficiency ◽

Clot Formation Time

Abstract Background and Aims Urinary excretion of the fibrinolytic enzyme plasminogen has been identified as a characteristic feature of nephrotic syndrome (NS) in both human and experimental mouse models. Lack of plasminogen may lead to a hypercoagulable state and thrombosis, and mice with plasminogen deficiency have been shown to suffer from developing spontaneous thrombosis. However, the role of plasminogen in hypercoagulable state and thrombosis in an experimental nephrotic syndrome has not been investigated before. Method We investigated the relationship between plasminogen and a hypercoagulable state in an inducible nephrotic mouse model with conditional podocyte-specific podocin deletion (Nphs2Δipod * Plg+/+, n=12). The Nphs2Δipod mice with constitutive plasminogen knockout were used as negative plasminogen control (Nphs2Δipod * Plg-/-, n=15). All mice received a daily oral doxycycline administration for 2 weeks for NS induction. The last day of doxycycline treatment was set as day 0. Spot urine was collected daily for proteinuria and urinary plasmin activity measurement. Citrate blood was collected from each mouse before induction of NS, 7 days and 21 days after induction, respectively (Nphs2Δipod * Plg+/+ mice, n=4/timepoint; Nphs2Δipod * Plg-/- mice, n=5/timepoint). A global assessment of coagulation (extrinsic coagulation test, EX test) was examined by ClotPro® system. Besides, fibrinolysis was tested by adding tissue plasminogen activator (TPA test). Results According to the EX test, uninduced mice with plasminogen deficiency showed a significantly reduced clotting time (CT, Plg-/- vs. Plg+/+, 42 ± 1s vs. 54 ± 4s, p=0.0213), and decreased clot formation time (CFT, Plg-/- vs. Plg+/+, 82 ± 5s vs. 206 ± 28s p<0.0001) with a larger alpha-angle (Plg-/- vs. Plg+/+, 75 ± 1° vs. 66 ± 2°, p=0.0041). The maximum clot firmness (MCF) was significantly increased in uninduced plasminogen knockout mice (Plg-/- vs. Plg+/+, 45 ± 0.5mm vs. 32 ± 2.5mm p<0.0001). According to the TPA test, uninduced Nphs2Δipod *Plg-/-mice had a faster velocity of clot formation (α-angle, 75.6 ± 0.2° vs. 66.5 ± 1.6°, p=0.0254) and did not show any clot lysis in contrast to uninduced nphs2Δipod * plg+/+mice. After induction of NS, both Nphs2Δipod * Plg-/-mice and Nphs2Δipod * Plg+/+ mice developed massive proteinuria to a comparable extent (Plg-/- vs. Plg+/+on day 21, 218 ± 46mg/mg crea vs. 203 ± 28mg/mg crea), and plasminuria was detectable in nephrotic nphs2Δipod * plg+/+ mice. With the ongoing loss of plasminogen in the urine, CT and CFT was significantly reduced in nephrotic Nphs2Δipod * Plg+/+ mice. MCF was significantly increased with a faster velocity of clot formation measured by both the EX and TPA test. Moreover, clot lysis was significantly reduced. In nephrotic nphs2Δipod *plg-/-mice at day 21, there was also a tendency towards a decrease in CT, CFT and an increased velocity of clot formation. According to both EX and TPA test, there were no significant differences between the genotypes in nephrotic mice any more. Conclusion The results highlight that loss of plasminogen in the nephrotic state contributes to a hypercoagulable state with shortened clotting time, clot formation time, increased clot firmness, and most strikingly, loss of clot lysis. Changes in nephrotic wild-type mice were similar to mice with constitutive plasminogen deficiency, indicating that loss of plasminogen plays a role in the hypercoagulable state of nephrotic syndrome.

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Intraoperative Blood Loss during Induced Abortion: A Comparison of Anesthetics

Anesthesiology Research and Practice ◽

10.1155/2018/4051896 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Camille A. Clare ◽

Gabrielle E. Hatton ◽

Neela Shrestha ◽

Michael Girshin ◽

Andre Broumas ◽

...

Keyword(s):

Blood Loss ◽

Retrospective Chart Review ◽

First Trimester ◽

Induced Abortion ◽

Anesthetic Technique ◽

Anesthetic Techniques ◽

Intraoperative Blood Loss ◽

Anesthetic Agents ◽

Dilatation And Curettage ◽

Increased Risk

Objective. To determine whether there is a difference in intraoperative bleeding with inhalational versus noninhalational anesthetic agents for patients undergoing suction dilatation and curettage for first-trimester induced abortion.Methods. This is an IRB-approved retrospective chart review of the electronic medical records of patients undergoing induced abortion at gestational ages between 5 0/7 and 14 0/7 weeks of pregnancy at the New York City Health + Hospitals/Metropolitan. The records of 138 patients who underwent suction dilatation and curettage for induced abortion between June 2012 and June 2014 were reviewed for an association between anesthetic technique and intraoperative hemorrhage. Twenty patients received inhalational anesthetic agents, while 118 received intravenous anesthetics. Blood loss was estimated by the operating gynecologists.Results. The mean intraoperative blood loss for inhalational anesthetics (113.6 ml) was significantly higher than with noninhalational agents (40.2 ml) (p=0.007). Age, body mass index, and gestational age were not statistically different between the groups; the number of methylergonovine doses at induced abortion trended higher with inhalation anesthetics.Conclusions. The difference in blood loss between the two types of anesthetic techniques was statistically significant. These findings may be important for patients with significant anemia or at an increased risk of bleeding, such as those with unrecognized coagulopathies.

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Effect of Progesterone and Synthetic Progestins on Whole Blood Clot Formation and Erythrocyte Structure

Microscopy and Microanalysis ◽

10.1017/s1431927617000484 ◽

2017 ◽

Vol 23 (3) ◽

pp. 607-617 ◽

Cited By ~ 7

Author(s):

Albe C. Swanepoel ◽

Odette Emmerson ◽

Etheresia Pretorius

Keyword(s):

Whole Blood ◽

Blood Clot ◽

Thrombotic Event ◽

Clot Formation ◽

Erythrocyte Aggregation ◽

Erythrocyte Morphology ◽

Increased Risk ◽

Blood Clots ◽

Membrane Ultrastructure

AbstractCombined oral contraceptive (COC) use is a risk factor for venous thrombosis (VT) and related to the specific type of progestin used. VT is accompanied by inflammation and pathophysiological clot formation, that includes aberrant erythrocytes and fibrin(ogen) interactions. In this paper, we aim to determine the influence of progesterone and different synthetic progestins found in COCs on the viscoelasticity of whole blood clots, as well as erythrocyte morphology and membrane ultrastructure, in an in vitro laboratory study. Thromboelastography (TEG), light microscopy, and scanning electron microscopy were our chosen methods. Our results point out that progestins influence the rate of whole blood clot formation. Alterations to erythrocyte morphology and membrane ultrastructure suggest the presence of eryptosis. We also note increased rouleaux formation, erythrocyte aggregation, and spontaneous fibrin formation in whole blood which may explain the increased risk of VT associated with COC use. Although not all COC users will experience a thrombotic event, individuals with a thrombotic predisposition, due to inflammatory or hematological illness, should be closely monitored to prevent pathological thrombosis.

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The incidence and effect of coagulopathy on short-term outcomes in patients undergoing craniotomy following traumatic brain injury

Journal of Neuroanaesthesiology and Critical Care ◽

10.4103/jnacc-jnacc-13.17 ◽

2017 ◽

Vol 04 (02) ◽

pp. 085-090

Author(s):

Sonia Bansal ◽

Rohini Surve ◽

Madhusudhan Rao ◽

Bhadri Narayan ◽

Mariamma Philip ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Platelet Count ◽

Brain Injury ◽

Blood Loss ◽

Hospital Stay ◽

Point Of Care ◽

Length Of Hospital Stay ◽

Liver Function Tests ◽

Intraoperative Blood Loss ◽

Gcs Score

Abstract Background: Coagulopathy in isolated traumatic brain injury (TBI) is well-known, and studies have found an association between coagulopathy and unfavourable outcomes. This study was conducted to determine the incidence and causes of coagulopathy in patients with TBI undergoing craniotomy and its effect on post-operative outcome. Materials and Methods: The data collected was demographics, computed tomography diagnosis, post-resuscitation Glasgow Coma Scale (GCS) score, pre- and post-operative platelet count, liver function tests, intraoperative blood loss and transfusion, fluids infused and incidence of redo surgery. Point of care (Coaguchek XS) monitor was used to obtain prothrombin time and international normalised ratio (INR) at 24 h and 72 h of injury. Coagulopathy was defined as INR ≥1.3 and thrombocytopenia as platelet count ≤100,000/mcL. Outcome measures assessed were the length of hospital stay, GCS at discharge and in-hospital mortality. Results: In 166 patients, the average pre-operative GCS was 8.8 ± 3.6. The incidence of coagulopathy was 42.8% and increased to 55.6% on the 3rd day, and thrombocytopenia from 3.5% in the first 24 h increased to 14.7% at 72 h. Patients with coagulopathy had lower pre-operative admission GCS (median 7 vs. 9, P = 0.03), greater intraoperative blood loss and received more intravenous fluids. There was no difference in the incidence of post-operative haematomas, length of hospital stay and GCS at discharge or mortality. Conclusion: In patients with TBI, the incidence of coagulopathy increased at the end of 72 h. In this study, there was no difference in outcomes in patients who underwent craniotomy with deranged coagulation.

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Comparison of viscoelastic test results from blood collected near simultaneously from the jugular and saphenous veins in cats

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x20959612 ◽

2020 ◽

pp. 1098612X2095961

Author(s):

James Mack Fudge ◽

Katherine S Cano ◽

Bernie Page ◽

Unity Jeffery

Keyword(s):

Saphenous Vein ◽

Whole Blood ◽

Venous Blood ◽

Alpha Angle ◽

Clot Formation ◽

Blood Collection ◽

Test Results ◽

Blood Samples ◽

Saphenous Veins ◽

Clot Time

Objectives The aim of this study was to compare viscoelastic test results from samples collected from a jugular vein using a 20 G needle and a medial saphenous vein using a 22 G needle in cats presenting for elective ovariohysterectomy (OHE) or castration. Methods Forty apparently healthy cats (20 males and 20 females) presenting for elective OHE or castration were included in a prospective study observing viscoelastic test results from central and peripherally collected whole blood. Cats were anesthetized during blood collection with a standardized protocol including buprenorphine, ketamine, dexmedetomidine and isoflurane. Blood samples from jugular and saphenous veins were collected near simultaneously. Viscoelastic evaluations of whole blood were performed using a point-of-care device measuring clot time (CT), clot formation time (CFT), alpha angle (α), maximum clot formation (MCF), and amplitude at 10 and 20 mins (A10 and A20, respectively). Viscoelastometry continued post-clot time to determine a lysis index at 30 and 45 mins (LI30 and LI45, respectively) to assess fibrinolysis. Results Studied cats had a median age of 18 months (range 5 months to 5 years) and a median weight of 3.6 kg (range 2.7–5.9 kg). A total of 80 samples were available for analysis. While lysis indices were not different, viscoelastic measures of coagulation differed between sampling sites (CT, P <0.005; CFT, P = 0.01; α, P <0.05; MCF, P <0.0005; A10, P <0.0005; A20, P <0.0005). Conclusions and relevance Viscoelastic results from jugular venous blood samples appear to be more hypercoagulable than those collected from the medial saphenous vein, suggesting that the same site should be used consistently for serial monitoring or for collecting study data.

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STIMULATION OF FIBRINOLYSIS BY ACTIVATED PROTEIN C (APC)

10.1055/s-0038-1642961 ◽

1987 ◽

Author(s):

N J de Four ◽

R M Bertina ◽

F Havgrkate

Keyword(s):

Complex Formation ◽

Whole Blood ◽

Blood Platelets ◽

Blood Clot ◽

Protein S ◽

Clot Formation ◽

Clot Lysis ◽

Minor Role ◽

Human Proteins ◽

Pai 1

In 1960 Mammen and Seegers reported the discovery of a new protein (autoprothrombin II-A, APC) with both anticoagulant and profibrinolytic activity. They found that APC accelerated clot lysis in vitro and proposed that this was due to a reduction of plasmin - inhibitory activity. Many years later Comp et al (J Clin Inv 68: 1221) reported that the infusion of APC into dogs resulted in an increase in circulating plasminogen activator activity. This observation stimulated more extensive studies of the profibrinolytic effects of APC.In our laboratories we have studied the effect of human APC on clot lysis both in whole blood (human) and in a system of purified human proteins. In these systems 125I-labelled fibrinogen was incorporated in a clot formed after the addition of Jombin (complete clot formation within 5 min) and the subsequent lysis of this clot was followed by measuring the release of I-labelled fibrin degradation products (FDP) into the supernatant. Human t-PA was added to the system to achieve complete lysis of the clot within a few hours.When APC was added to citrated whole blood before clot formation, it was found to accelerate clot lysis in a dose dependent way. This effeg| was specific for APC and dependent on an intact active site, on the presence of protein S (the protein cofactor of APC) and Ca . The presence of APC did not influence the composition of the FDP formed, as analysed by means of SDS-polyacry-1 amide gel electroforesis, and its effect was found to be independent of the presence or absence of a.-antiplasmin.Subsequently we developped a clot lysis system using the purified human proteins of the fibrinolytic system: fibrinogen, FXIII, t-PA, PAI-1 (from human endothelial cells), glu-plasminogen and a -antiplasmin. In this system clot lysis was dependent on the concentrations of plasminogen, -antiplasmin, t-PA and PAI-1, but independent on the thrombin concentration and the presence or absence of phospholipids (purified from human brain). In the absence of PAI-1, no effect of APC on clot lysis was observed. However, in the presence of PAI-1, APC accelerated clot lysis. This effect was independent of the presence or absence of phospholipids and/or protein S and could be explained by the observation that APC can form a complex with PAI-1 (~ 95 kd) and under certain conditions even can convert active PAI-1 (~ 46 kd) into an inactive degradation product (~ 42 kd). However, complex formation is relatively slow anti high PAI-1 concentrations are needed to observe the reaction. The addition of protein S or phospholipids in the presence of Ca did not stimulate complex formation. Therefore, it seems highly unlikely that neutralization of PAI-1 by APC is responsible for the profibrinolytic effect of APC in the whole blood clot lysis.A completely different explanation for the profibrinolytic effect of APC was suggested by the observation that the addition of blood-platelets to the system of purified fibrinolytic components introduced a dependence of the clot lysis rate on the thrombin concentration (decrease in clot lysis at increasing thrombin concentration). This finding opened the possibility that APC stimulated fibrinolysis by reducing the effective thrombin concentration. Subsequent experiments using the whole blood clot lysis system revealed that in the presence of anti-FX antibodies clot lysis was no longer accelerated by APC, while the actual rate of clot lysis depended on the concentration of thrombin added.We like to propose, that in a blood clot lysis system APC most likely accelerates fibrinolysis by reducing the effective thrombin concentration; if at all, neutralization of PAI-1 may play only a minor role.

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Monitoring of hemostasis in cardiac surgical patients: impact of point-of-care testing on blood loss and transfusion outcomes

Clinical Chemistry ◽

10.1093/clinchem/43.9.1684 ◽

1997 ◽

Vol 43 (9) ◽

pp. 1684-1696 ◽

Cited By ~ 96

Author(s):

George J Despotis ◽

J Heinrich Joist ◽

Lawrence T Goodnough

Keyword(s):

Blood Loss ◽

Point Of Care ◽

Coagulation Factor ◽

Surgical Patients ◽

Patient Specific ◽

Blood Component ◽

Multiple Point ◽

Excessive Bleeding ◽

Transfusion Requirements ◽

Increased Risk

Abstract Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Strategies to optimize administration of heparin and protamine and the assessment of their effects on coagulation are evolving in cardiac surgical patients. Two recent evaluations have focused on the use of multiple point-of-care (POC) coagulation assays for patient-specific adjustment of heparin and protamine dosage. These studies indicate that blood loss and transfusion requirements in cardiac surgical patients may be reduced with more accurate control of heparin anticoagulation and its reversal. Blood component administration in patients with excessive post-CPB bleeding is generally empiric in part, related to turnaround times of laboratory-based tests. Methods are now available for rapid, POC assessment of coagulation to allow appropriate, targeted therapy for acquired hemostatic abnormalities. Recent studies indicate that a rapid evaluation of thrombocytopenia and coagulation factor deficiencies with POC tests can facilitate the optimal administration of pharmacologic and transfusion-based therapy in patients who exhibit excessive bleeding after CPB. POC tests that assess platelet function have been developed, and their use may facilitate identification of which patients at risk for excessive blood loss may respond to pharmacologic interventions such as desmopressin acetate or antifibrinolytic agents.

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Platelet Apoptosis and PAI-1 Content Are Involved in the Procoagulant Profile of Immune Thrombocytopenia Patients Responders to Agonists of Thrombopoietin Receptor.

Blood ◽

10.1182/blood-2018-99-115898 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3738-3738

Author(s):

Raul Justo Sanz ◽

Elena Monzón Manzano ◽

Ihosvany Fernandez-Bello ◽

Teresa Álvarez-Roman ◽

Mónica Martín ◽

...

Keyword(s):

Research Funding ◽

Immune Thrombocytopenia ◽

Alpha Angle ◽

Clot Formation ◽

Clot Lysis ◽

Control Group ◽

Healthy Controls ◽

Prothrombinase Complex ◽

Thrombopoietin Receptor ◽

Pai 1

Abstract Background: The treatment goal for patients with immune thrombocytopenia (ITP) is to raise platelet counts to levels that minimize or stop bleeding. Thrombopoietin receptor agonists (TPO-RAs) have been successfully and extensively employed as second-line therapy for ITP. TPO-RAs, however, have a small but significant increase in the risk of thrombosis. Aim: The aim of this study was to elucidate the mechanisms involved in the procoagulant effect of TPO-RAs. Methods: This is a prospective, observational and transversal study. Eighty-two patients with chronic primary ITP, 40 without treatment for at least six months (UT-ITP) and 42 responders to TPO-RA therapy (64.3% with eltrombopag and 35.7 % with romiplostim) were recruited. One hundred and twelve healthy participants were also included. ROTEM® (naTEM test: only recalcification) was performed on platelet rich plasma adjusted to a platelet count of 25 x 109/L. Clotting time (CT, time from start of measurement until 2 mm of amplitude [in seconds], alpha angle, which reflects the rate of fibrin polymerisation (tangent to the curve at 2 mm amplitude [in degrees]), maximum clot firmness, which reflects the maximum tensile strength of the thrombus (MCF, [in mm]) and LI60, which describes the percentage of maximum clot strength present at 60 min (in %), were recorded. Surface exposure of phosphatidylserine (PS), active caspase-3, -8 or -9 and prothrombinase complex binding to platelets were assessed by flow cytometry. Plasma and platelet levels of PAI-1 were determined by ELISA (eBioscience Ltd., Hatfield, United Kingdom). The effect of TPO and romiplostim on PAI-1 content of MEG-01 cells was evaluated by Western blot. Three MEG-01 cell cultures were initiated simultaneously: control without drugs and treated with either TPO (100 ng/mL) or romiplostim (53 μg/mL). Samples were collected at the start and after 24, 48 and 72 hours to determine the PAI-1 content. The statistical analysis was performed using SPSS 9.0 software (SPSS Inc., Chicago, Illinois, USA). Results: The ROTEM® studies showed significant differences in the dynamics of clot formation when comparing the control with ITP samples. There was a delay in clot formation in the UT-ITP group, as observed by a prolonged CT [expressed as median (p25-p75): control: 516 (490- 633) s; UT-ITP: 938 (914-1348) s, p<0.001], and a diminished alpha angle (mean±SD; control: 61.7±5.6 degrees; UT-ITP: 49.2±7.3 degrees, p<0.05). Nevertheless, samples from patients with UT-ITP reached the same MCF as those from healthy controls (control: 45.3±2.4 mm; UT-ITP: 46.9±3.7 mm). On the other hand, patients with ITP undergoing TPO-RA therapy presented an initial clot formation similar to that of the control group [expressed as median (p25-p75): CT, 672 (598-928) s; alpha angle, 55.8±5.8 degrees] but achieved a higher MCF (53.1±4.5 mm, p<0.05) and a reduced clot lysis after 60 min (control: 91.8±4.0%; UT-ITP: 93.7±4.0%, TPO-RA ITP: 97.6±1.7, p<0.05). Higher values of MCF observed with platelets from ITP patients treated with TPO-RAs might be a consequence of their augmented apoptosis signs: platelets from this group exposed more PS than controls and this situation was accompanied by an increased activity of caspases-3,7, -8 and -9 (Figure 1 A and B). Moreover, platelets from ITP patients on treatment with TPO-RAs bound more prothrombinase complex than platelets from UT-ITP patients and healthy controls (Figure 1 C). Reduced clot lysis observed in ITP patients treated with TPO-RA was due, at least in part, to increased plasma and platelet levels of PAI-1 (Table 1). Increase in platelet content of PAI-1 might be the result of the effect of TPO-RAs during megakaryopoiesis since treatments of MEG-01 cells with TPO or romiplostim induced a 3-fold increase in their endogenous PAI-1 content after an incubation period of 48 hs. Conclusion: The patients with ITP undergoing TPO-RAs therapy presented a procoagulant profile due to the formation of a more fibrinolysis-resistant clot because of increased platelet and plasma PAI-1 levels. Moreover, platelets from this group of patients showed more signs of apoptosis that causes a higher exposure of PS and, consequently, a larger surface for the binding of the prothrombinase complex. Work supported by grant from FIS-FEDER PI15/01457. NB holds a Miguel Servet II (FIS-FEDER CP14/00024). Disclosures Álvarez-Roman: SOBI: Consultancy; NovoNordisk: Consultancy; Shire: Consultancy. Jimenez-Yuste:Grifols: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; CSL Behring: Consultancy; Bayer: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Sobi: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding. Butta:FIS-Fondos FEDER: Research Funding.

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Detection of the State of Thrombotic Readiness in Rats under One-Time Suprathreshold Physical Activity of Various Durations by Means of Thromboelastography

Journal of Siberian Federal University Biology ◽

10.17516/1997-1389-0312 ◽

2019 ◽

pp. 460-469

Author(s):

Alexander A. Blazhko ◽

Igor I. Shakhmatov ◽

Igor V. Kovalev ◽

Valeriy I. Kiselev ◽

Yuliya A. Bondarchuk ◽

...

Keyword(s):

Physical Activity ◽

Alpha Angle ◽

The State ◽

Clot Formation ◽

Clot Lysis ◽

Coagulation Time ◽

Integrated Method ◽

Hemostatic System ◽

The One ◽

Maximum Clot Firmness

Suprathreshold physical activity causing distress in the organism can lead to the damage of various organs and systems including the hemostatic system. A modern integrated method of the hemostatic system assessment is thromboelastography. The purpose of the present study was to evaluate the state of the hemostatic system under one-time suprathreshold physical activity of various durations by means of thromboelastography. Experimental groups of rats were exposed to 4-hour and 8-hour physical activities in the form of forced running on a moving platform with the speed of 6-8 m/min. Immediately after the one-time physical activity, blood samples taken from rats were examined using the thrombelastograph in the Natem mode for 35 minutes. The 4-hour physical activity caused a reduction in coagulation time (CT) and an increase in the alpha angle and the maximum clot firmness (MCF). After the 8-hour activity, the thrombelastograph registered a reduction in coagulation time (CT), an increase in the alpha angle, a decrease in the clot formation time (CFT), a decrease in the maximum clot firmness (MCF), and a reduction in the maximum clot lysis (ML). The 4-hour physical activity resulted in partial activation of the hemostatic system without changing the fibrinolytic activity of blood plasm. The changes revealed in thromboelastography parameters indicate a high risk of the development of thrombotic readiness. The 8-hour physical activity causes a shift of the hemostatic system parameters in rats towards the increased clot formation: hypercoagulation, fibrinogen and platelet consumption, inhibition of fibrinolysis. The combination of changes in thromboelastogram parameters is indicative of the development of thrombotic readiness

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Abstract 354: Clots Are Potent Triggers of Inflammatory Cell Gene Expression: Indications for Timely Fibrinolysis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.354 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Robert A Campbell ◽

Adriana Vieira-de-Abreu ◽

Jesse W Rowley ◽

Zechariah G Franks ◽

Matthew T Rondina ◽

...

Keyword(s):

Gene Expression ◽

Whole Blood ◽

Inflammatory Responses ◽

Vascular Diseases ◽

Clot Formation ◽

Clot Lysis ◽

Dependent Manner ◽

Plasma Clot ◽

Monocyte Chemoattractant Protein 1

Objective: Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown. Determine if clot formation and lysis regulates the expression of human monocyte-derived genes that modulate vascular diseases. Approach and Results: We performed Next Generation RNA sequencing on monocytes extracted from whole blood clots. Thousands of mRNAs were differentially expressed by monocytes from clotted versus unclotted whole blood, including upregulation of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1). Clotted plasma also increased expression of IL-8 and MCP-1, which far exceeded responses observed in LPS-stimulated monocytes. Upregulation of IL-8 and MCP-1 occurred in a thrombin-independent, but fibrin-dependent manner. Fibrinolysis initiated shortly after plasma clot formation (i.e., 1-2 hours) reduced the synthesis of IL-8 and MCP-1, while delayed fibrinolysis was far less effective. Consistent with these in vitro models, monocytes embedded in unresolved thrombi from patients undergoing thrombectomy stained positively for IL-8 and MCP-1. Conclusions: These findings demonstrate that clots are potent inducers of monocyte gene expression, and that timely fibrinolysis attenuates inflammatory responses. Dampening of inflammatory gene expression by timely clot lysis may contribute to the clinically-proven efficacy of fibrinolytic drug treatment within hours of stroke onset.

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