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

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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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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In Vitro Evaluation of the Effect of Haemodilution with Dextran 40 on Coagulation Profile as Measured by Thromboelastometry and Multiple Electrode Aggregometry

Anaesthesia and Intensive Care ◽

10.1177/0310057x1704500506 ◽

2017 ◽

Vol 45 (5) ◽

pp. 562-568 ◽

Cited By ~ 2

Author(s):

P. C. A. Kam ◽

J. P. C. Liou ◽

K. X. F. Yang

Keyword(s):

Normal Saline ◽

Alpha Angle ◽

Formation Time ◽

Clot Formation ◽

Coagulation Time ◽

Dextran 40 ◽

Multiple Electrode Aggregometry ◽

Clot Formation Time ◽

Multiple Electrode

We evaluated the effects of haemodilution with either dextran 40 or 0.9% normal saline on coagulation in vitro using rotational thromboelastometry (ROTEM®, Pentapharm Co., Munich, Germany) and multiple electrode aggregometry (Multiplate® Platelet Function Analyser, Dynabyte, Munich, Germany). Venous blood samples obtained from 20 healthy volunteers were diluted in vitro with dextran 40 or normal saline by 5%, 10% and 15%. Fibrinogen concentration, ROTEM-EXTEM® (screening test for the extrinsic coagulation pathway), FIBTEM® (an EXTEM-based assay of the fibrin component of clot) parameters including coagulation time, clot formation time, alpha angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each level of haemodilution. Dextran 40 at 15% haemodilution significantly prolonged coagulation time, clot formation time and significantly decreased the alpha angle and maximal clot firmness (EXTEM amplitude at five minutes [A5] and ten minutes [A10]) compared with normal saline. The FIBTEM assay (maximal clot firmness and FIBTEM A5 and A10) showed a marked decrease in maximal clot firmness at all dilutions suggesting impaired fibrinogen activity and a risk of bleeding. Multiple electrode aggregometry did not demonstrate any platelet dysfunction. Haemodilution with dextran 40 causes significant impairment in clot formation and strength compared to saline haemodilution and undiluted blood. At the levels of in vitro haemodilution designed to reflect the clinical use of dextran infusions, no significant fibrinolysis or platelet inhibition was observed.

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Comparison of standard coagulation tests and rotational thromboelastometry for hemostatic system monitoring during orthotopic liver transplantation: Results from a pilot study

Medicinski pregled ◽

10.2298/mpns1510301n ◽

2015 ◽

Vol 68 (9-10) ◽

pp. 301-307 ◽

Cited By ~ 3

Author(s):

Sladjana Novakovic-Anucin ◽

Dusica Kosanovic ◽

Sanja Gnip ◽

Visnja Canak ◽

Velibor Cabarkapa ◽

...

Keyword(s):

Liver Transplantation ◽

Platelet Count ◽

Fibrinogen Level ◽

Activated Partial Thromboplastin Time ◽

Coagulation Time ◽

Rotational Thromboelastometry ◽

Hemostatic System ◽

Coagulation Tests ◽

Clot Formation Time ◽

Maximum Clot Firmness

Introduction. During liver transplantation, continuous laboratory monitoring of complex changes of the hemostatic system is necessary. The aim of this study was to compare two methods of monitoring: standard coagulation tests and rotational thromboelastometry. Material and Methods. The study included 17 patients who had undergone orthotopic liver transplantation in the Clinical Centre of Vojvodina, Serbia in the period from June 2008 to October 2012. The coagulation parameters (platelet count, activated partial thromboplastin time, prothrombin time and fibrinogen level) were compared with the thromboelastometric parameters (coagulation time, clot formation time and maximal clot firmness). Results. The results showed a statistically significant correlation between the platelet count and maximum clot firmness of the intrinsically (r=0.51, p<0.001) and extrinsically activated thromboelastometric assays (r=0.64, p<0.001). The fibrinogen level and maximum clot firmness of the fibrinogen thromboelastometric test correlated significantly as well (r=0.44, p=0.002). No significant correlations were found among the activated partial thromboplastin time, prothrombin time, coagulation time and clot formation time. Conclusion. For an adequate perioperative monitoring of the dynamic intraoperative hemostatic changes and the optimal use of blood derivatives during liver transplantation, the combined application of standard coagulation tests and rotational thromboelastometry should be considered whenever possible. Science and Technological Development, Republic of Serbia

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

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x20959610 ◽

2020 ◽

pp. 1098612X2095961

Author(s):

James Mack Fudge ◽

Bernie Page ◽

Amy Mackrell ◽

Inhyung Lee ◽

Unity Jeffery

Keyword(s):

Blood Loss ◽

Whole Blood ◽

Point Of Care ◽

Alpha Angle ◽

Clot Formation ◽

Clot Lysis ◽

Intraoperative Blood Loss ◽

Increased Risk ◽

Midline Approach ◽

Clot Formation Time

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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STATE OF THE BLOOD COAGULATION SYSTEM IN CHILDREN WITH VASCULAR MALFORMATIONS AND INFLAMMATORY DISEASES OF THE MAXILLOFACIAL AREA

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-1-153-165 ◽

2021 ◽

Vol 100 (1) ◽

pp. 153-165

Author(s):

D.E. Pavlova ◽

◽

A.V. Petukhov ◽

E.M. Tolstova ◽

S.V. Iamatina ◽

...

Keyword(s):

Growth Rate ◽

Inflammatory Diseases ◽

Vascular Malformations ◽

Alpha Angle ◽

Maximum Amplitude ◽

The State ◽

Clot Formation ◽

Control Group ◽

Maxillofacial Region ◽

Integrated Methods

The article presents the results of a study of hemostasis in children with vascular malformations and inflammatory diseases of the maxillofacial region using standard and integrated methods for assessing hemostasis. Objective of the research: to assess the state of the hemostatic system in children with vascular malformations and inflammatory diseases of the maxillofacial region using standart and integrated methods. Materials and methods: on the basis of St. Vladimir's Children's Clinical Hospital in 2015–2019. А prospective open controlled comparative nonrandomized selective study of coagulological status was performed using standard coagulological tests and integral methods for assessing hemostasis (thromboelastography – TEG, thrombodynamics – TD) in 105 patients with lymphatic, lymphovenous, venous, arteriovenous vascular malformations of the head and neck (age 6 [5; 9] years), 47 children with infectious and inflammatory diseases of the maxillofacial area (age 10 [4; 17] years). The control group included 37 children (age 9 [5; 13] years). Results: according to the data, in most patients with vascular malformations, the coagulogram did not reveal pronounced shifts in hemostasis. TEG indices demonstrated hypercoagulability in vascular malformations: the onset time of clot R formation was 11,20 [8,72; 15,75] min (the norm is 9–27 min); clot K formation time was reduced to 3,90 [2,30; 6,02] min (the norm is 2–9 min). According to TD data, the process of fibrin clot growth in patients with vascular malformations accelerated: the clot V growth rate was 32,80 [28,70; 40,20] μm/min (norm 20–29 μm/min), an increase in the rate was observed mainly due to the acceleration of the clot growth initiation. The formation of spontaneous clots was noted in 32% of cases. In the group of infectious and inflammatory diseases of the maxillofacial area, the hypercoagulation was most pronounced: fibrinogen level significantly increased compared with the control group (3,21 [2,69; 4,72] g/l vs 2,69 [2,37; 3,17 ] g/l; p=0,0025). The soluble fibrin monomer complex (SFMC) indicator statistically significantly increased to 5,50 [0,00; 6,00] mg% (1,50 [0,00; 5,00] mg% in the control group, p=0,006). TEG showed a decrease in R (11,10 [8,82; 14,32] min vs 15,2 [11,8; 20,6] min; p=0,001) and K (3,65 [2,45; 5,10] min vs 6,70 [4,20; 8,25] min; p=0,0001), statistically significant compared to the control group. The alpha angle increased to 45,70 [36,20; 56,02] (30,8 [23,25; 41,15] in the control group, p=0,0001); maximum amplitude (MA) and clot density (G) increased in comparison with the control: 56,6±8,68 mm vs 48,10±6,20 mm; p=0,0001 and 6,50 [4,80; 8,00] Kd/sc vs 4,60 [3,60; 5,30] Kd/sc; p=0,0001. The TD indices in patients in this group also reflected a hypercoagulable state: the rate of V clot formation increased to 38,60 [33,00; 51,40] μm/min (30,45 [27,60; 33,30] μm/min in the control group, p<0,0001); the initial rate of clot formation also increased – 63,50 [59,10; 68,62] μm/min (58,74 [56,57; 64,20] μm/min in the control group, p=0,0055); the size (CS) and density (D) of the clot increased – 1425,5 [1265,7; 1505,2] μm (1251,00 [1168,82; 1322,50] μm in the control group, p=0,0029) and 25 362,50 [21 922,00; 29 210,50] conv. units (22 883,00 [20 807,25; 24 658,64] conv. units in the control group, p=0,0208). Spontaneous clots were formed in 50% of cases. Conclusion: integral tests are a sensitive method for assessing the state of hemostasis in patients with vascular malformations and infectious and inflammatory diseases. The revealed hypercoagulable shifts in the form of clot growth rate acceleration work as the basis for a thorough dynamic assessment of the hemostasis system in children with vascular malformations and infectious-inflammatory diseases in order to prevent thrombotic complications.

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Reaction of hemostasis system in hypercapnic hypoxia after the course of mexidol assessed by the method of thromboelastography

Kazan medical journal ◽

10.17816/kmj2018-936 ◽

2018 ◽

Vol 99 (6) ◽

pp. 936-941

Author(s):

S V Moskalenko ◽

I I Shakhmatov ◽

Yu A Bondarchuk ◽

O V Alekseeva ◽

O M Ulitina

Keyword(s):

Alpha Angle ◽

Maximum Intensity ◽

Clot Formation ◽

Male Rats ◽

Clot Lysis ◽

Standard Diet ◽

Single Exposure ◽

Average Mass ◽

Hemostasis System ◽

Hypercapnic Hypoxia

Aim. To study the reaction of hemostasis system to a single effect of hypercapnic hypoxia of maximum intensity in rats and possibility of correcting hemostasis disorders by means of a preliminary course of an antihypoxant - mexidol. Methods. The study involved sexually mature male rats (48 specimens) of the Wistar line with an average mass of 274.0 ± 32.0 g. The rats were kept on a standard diet, food and water were fed once a day between 10 and 11 hours. In the evening, animals underwent a single hypercapnic hypoxia in a special flow chamber. The state of hypercapnic hypoxia of maximum intensity was modeled at O2 content of 5.0 %, CO2 - 5.0 % during a single 20-minute exposure. As a training regimen, a 30-fold course of mexidol was used, the drug was administered intraperitoneally to rats at a dose of 50 mg/kg for 1.5 hours prior to exposure to hypercapnic hypoxia. Results. After a single exposure to hypercapnic hypoxia of maximum intensity, shortening of the onset of clot formation, an increase of alpha angle, and maximum clot density were recorded. Also, the clot formation time shortened and the maximum clot lysis index increased. With a single exposure to hypercapnic hypoxia of maximum intensity after the course of mexidol, a decrease in the maximum clot density was recorded. Conclusion. A single exposure to hypercapnic hypoxia of maximum intensity was characterized by a shift of hemostatic potential toward hypercoagulability along with fibrinolytic system activation. The course use of antihypoxant mexidol, preceding hypercapnic hypoxia of maximum intensity, significantly reduces the risk of clot formation.

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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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Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness

BioMed Research International ◽

10.1155/2015/593938 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Marc Schaber ◽

Veronika Leichtfried ◽

Dietmar Fries ◽

Maria Wille ◽

Hannes Gatterer ◽

...

Keyword(s):

Acute Mountain Sickness ◽

Activated Partial Thromboplastin Time ◽

Reference Ranges ◽

Simulated Altitude ◽

Coagulation Time ◽

Hemostatic System ◽

Mountain Sickness ◽

Healthy Participants ◽

Generation Test ◽

Maximum Clot Firmness

Introduction. The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls.Materials and Methods. 37 healthy participants were passively exposed to 12.6% FiO2(simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used.Results. AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired samplet-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test).Conclusions. All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected.

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Influence of Moderate and Strenuous Daily Physical Activity on Fibrinolytic Activity of Blood: Possibility of Plasminogen Activator Stores Depletion

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646834 ◽

1979 ◽

Vol 41 (04) ◽

pp. 745-755 ◽

Cited By ~ 22

Author(s):

Dušan Keber ◽

Mojca Stegnar ◽

Irena Keber ◽

Bojan Accetto

Keyword(s):

Physical Activity ◽

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Regular Physical Activity ◽

Clot Lysis ◽

Moderate Activity ◽

Lysis Time ◽

Strenuous Activity ◽

Activity Measurements ◽

Clot Lysis Time

SummaryFibrinolysis was studied in 10 alpinists during regular physical activity of different intensity. Blood was sampled at rest and after exposure to submaximal workload on the treadmill on three occasions: before and after 6 months physical conditioning (moderate physical activity), and after 6 weeks of an alpinistic expedition (strenuous physical activity). Measurements included submaximal working capacity, fibrinogen, euglobulin clot lysis time (ELT), whole plasma clot lysis time, and estimations derived from ELT - percent increase in fibrinolytic activity after exercise (RFS), and absolute increase in fibrinolytic activity after exercise (PAR).Regular moderate activity increased the resting level of ELT, but strenuous activity decreased is. After each treadmill testing, a marked increase in fibrinolytic activity was observed. RFS was unaltered at all three testings. PAR increased after moderate activity, but decreased after strenuous activity.The results indicate that regular physical activity can lead from enhanced to decreased resting activity of plasminogen activator in blood. It is presumed that increased release of activator during prolonged stress causes partial depletion of endothelial stores with the consequence of decreased activator activity in the blood.

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The Munich conference of Minister-Presidents of German lands in 1947

OOO Zhurnal Voprosy Istorii ◽

10.31166/voprosyistorii202010statyi28 ◽

2020 ◽

Vol 2020 (10-2) ◽

pp. 86-98

Author(s):

Ivan Popov

Keyword(s):

The State ◽

State Governments ◽

The West ◽

Constitutional Development ◽

The Moment ◽

The One

The paper deals with the organization and decisions of the conference of the Minister-Presidents of German lands in Munich on June 6-7, 1947, which became the one and only meeting of the heads of the state governments of the western and eastern occupation zones before the division of Germany. The conference was the first experience of national positioning of the regional elite and clearly demonstrated that by the middle of 1947, not only between the allies, but also among German politicians, the incompatibility of perspectives of further constitutional development was existent and all the basic conditions for the division of Germany became ripe. Munich was the last significant demonstration of this disunity and the moment of the final turn towards the three-zone orientation of the West German elite.

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