scholarly journals “Global” assays of hemostasis in modern obstetrical practice

2019 ◽  
Vol 100 (6) ◽  
pp. 958-964
Author(s):  
I G Mustafin ◽  
T E Kurmanbaev ◽  
A A Shmidt ◽  
Yu L Timoshkova ◽  
K M Atayants
Keyword(s):  
Low Frequency ◽  
Screening Tests ◽  
Coagulation System ◽  
Screening Methods ◽  
Limited Information ◽  
Hemostatic System ◽  
Significant Difference ◽  
Global Tests ◽  
Low Sensitivity ◽  
Generation Test

It is known that during pregnancy, the hemostatic system, like the rest of the body's systems, undergoes certain changes: there is a gradual increase in the activity of coagulation unit of the hemostasis reaching a maximum before childbirth. However, if pregnancy is complicated by various hypertensive conditions, such as preeclampsia, an imbalance is observed in the hemostasis: against the background of an increase in the activity of coagulation link, depletion of anticoagulation factors and dysfunction of fibrinolytic system are observed. All these changes create a pathogenetic basis for the occurrence of severe thrombohemorrhagic complications that are fatal for both mother and fetus. Thus, the timely detection of these violations is an important task for modern obstetrics. Unfortunately, the applied screening methods for assessing the hemostasis system in practice provide extremely limited information: the tests have low sensitivity to hypercoagulation, as well as moderate to hypocoagulation, they do not allow to fully evaluate the dynamics of coagulation process in real time. In addition, when performing the same tests with reagents of different companies in the same patient, there may be a significant difference in the results. Disadvantages of screening tests became the reason for the search for a test to assess the functioning of the hemostatic system, which can reflect the complete picture of the state of blood coagulation system, and not of its individual links. Such tests are the so-called global tests for assessing the hemostatic system: thrombin generation test, thromboelastography, low-frequency piezothromboelastography and thrombodynamics. Each of the listed global tests has been successfully tested in obstetric and gynecological practice.

COMPARATIVE PHARMACODYNAMICS OF SUBCUTANEOUSLY ADMINISTERED HEPARIN (HEP) AND A LOW MOLECULAR WEIGHT HEPARIN (LMWH) AS STUDIED BY AN EX VIVO FIBRINOPEPTIDE A (FPA) GENERATION TEST

1987 ◽  
Author(s):  
B Spyropulos ◽  
J Fareed ◽  
R M Emanuel ◽  
D Hoppensteadt
Keyword(s):  
Ex Vivo ◽  
Coagulation System ◽  
Low Molecular Weight ◽  
Global Tests ◽  
Pharmacologic Effect ◽  
The Individual ◽  
Individual Enzyme ◽  
Dose Dependent ◽  
Generation Test ◽  
Antiprotease Activity

Subcutaneously administered heparins do not produce any sizeable effects on the global tests and their activities are currently measured using amidolytic anti Xa and anti Ila assays. These methods are sensitive only to the individual enzyme and do not reflect other biologic actions. We have used a thromboplastin C activated FPA generation test to measure the pharmacodynamic effects of subcutaneously administered HEP and a LMWH in primates. 400μl of citrated plasma was equilibrated at 37°C for 2 minutes and was activated with 100 μl thromboplastin diluted in .020M CaCl2. FPA was generated for 2 min, inhibited with 50 μl of an inhibitor cocktail and measured using an RIA kit (Mallinckrodt, St, Louis, M0). Marked dose dependent suppression of the FPA generation was noted for varying periods of time by both HEP and LMWH. Stronger effects were observed with LMWH, suggesting better subcutaneous bioavailability and functional effects. Significant FPA generation inhibition was observed even when there was no circulating antiprotease activity present in the plasma. These results suggest that FPA generation test is a sensitive test to measure the pharmacologic effect of heparins. Furthermore the FPA generation tests can be modified to activate the coagulation system at certain sites to study the effect of heparins.

scholarly journals Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

2021 ◽  
Author(s):  
Allegra Ferrari ◽  
Isabelle Neefs ◽  
Sarah Hoeck ◽  
Marc Peeters ◽  
Guido Van Hal
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Screening Tests ◽  
Screening Methods ◽  
Exhaled Breath ◽  
Sample Collection ◽  
Screening Programs ◽  
Crc Screening ◽  
Low Sensitivity ◽  
Standard Colonoscopy

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

scholarly journals Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1820
Author(s):  
Allegra Ferrari ◽  
Isabelle Neefs ◽  
Sarah Hoeck ◽  
Marc Peeters ◽  
Guido Van Hal
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Screening Tests ◽  
Screening Methods ◽  
Exhaled Breath ◽  
Sample Collection ◽  
Screening Programs ◽  
Crc Screening ◽  
Low Sensitivity ◽  
Standard Colonoscopy

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs, which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring. In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques, the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath, and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63–100%, 90–95%, and 47–97%, respectively) while minimizing stress and discomfort for the patient.

scholarly journals Аspects of the methodology of laboratory studies of hemostasis in pediatric hematology-oncology and general approaches in the pathology of hemostasis in leukemia

2018 ◽  
Vol 5 (3) ◽  
pp. 74-88
Author(s):  
E. M. Koltsova ◽  
A. N. Balandina ◽  
E. A. Seregina ◽  
A. V. Poletaev ◽  
T. A. Vuymo ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Thrombin Generation ◽  
Clinical Manifestations ◽  
Underlying Disease ◽  
Screening Tests ◽  
Coagulation System ◽  
Central Vein ◽  
Standard Laboratory ◽  
Pediatric Hematology ◽  
Generation Test

Children with acute leukemia are faced with high risks of thrombotic and hemorrhagic complications. The pathogenesis of haemostasis disorders in hemoblastoses is complex because, in addition to the disease itself, the aggressiveness of the therapy and the need for numerous invasive manipulations also make a significant contribution. Patients with hemoblastoses are equally susceptible to thrombosis and hemorrhage, which makes it possible to speak of multidirectional shifts in the balance of the hemostatic system in each individual patient. Standard laboratory hemostasis tests (clotting times, marker tests) are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostasis, and in do not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests designed to assess the coagulation balance, such as thromboelastography, thrombin generation test, and thrombodynamics, can be the alternative for the standard coagulation assays. The review focuses on the mechanisms of various laboratory hemostasis tests, as well as an assessment of their informative value in frequent complications of the underlying disease (sepsis leading to the development of disseminated intravascular coagulation (DIC) syndrome, thrombocytopenia) and catheterization, which is present in the majority of patients with hemoblastosis. General screening tests of the blood coagulation system have little diagnostic value in the DIC syndrome in patients with acute leukemia, mainly due to their insensitivity to hypercoagulability. Standard markers (for example, D-dimers) are non-specific and only confirm the clinical manifestations of clotting disorder in sepsis and septic shock, but are unable to predict the dynamics of this process at earlier stages of the inflammatory response. In this case, the thrombin generation test and thrombodynamics make it possible to reveal the hypercoagulable phase of the DIC syndrome. Thrombocytopenia accompanies almost all protocols of chemotherapy. In this case, the degree of bleeding does not always depend only on the concentration of platelets, since chemotherapeutic drugs can affect not only the quantity, but also the functional characteristics of platelets, which are not determined by standard examination of patients. The catheterization that accompanies the treatment of hemoblastoses is the leading cause of thrombosis in children with acute leukemia. Thromboembolism of the pulmonary artery due to thrombosis in the central vein system occurs in 8–15 % of patients. The prediction of catheter-associated thromboses using standard laboratory methods for assessing the state of the hemostasis is not possible. Absence of sensitive tests in modern diagnostic schemes leads to the fact that the attending physician is forced to focus exclusively on the clinical picture of thrombosis or bleeding. The development of new functional methods of hemostasis allows one to think that today the existing standard panel of coagulation tests can be expanded and made much more informative in terms of the prediction of thrombohemorrhagic complications in pediatric hematology-oncology.

Real Ear Sound Pressure Levels Developed by Three Portable Stereo System Earphones

1992 ◽  
Vol 1 (4) ◽  
pp. 52-55 ◽  
Author(s):  
Gail L. MacLean ◽  
Andrew Stuart ◽  
Robert Stenstrom
Keyword(s):  
High Frequency ◽  
Sound Pressure ◽  
Low Frequency ◽  
Test System ◽  
Output Frequency ◽  
Frequency Effects ◽  
Adult Men ◽  
Frequency Responses ◽  
Significant Difference ◽  
Sound Pressure Levels

Differences in real ear sound pressure levels (SPLs) with three portable stereo system (PSS) earphones (supraaural [Sony Model MDR-44], semiaural [Sony Model MDR-A15L], and insert [Sony Model MDR-E225]) were investigated. Twelve adult men served as subjects. Frequency response, high frequency average (HFA) output, peak output, peak output frequency, and overall RMS output for each PSS earphone were obtained with a probe tube microphone system (Fonix 6500 Hearing Aid Test System). Results indicated a significant difference in mean RMS outputs with nonsignificant differences in mean HFA outputs, peak outputs, and peak output frequencies among PSS earphones. Differences in mean overall RMS outputs were attributed to differences in low-frequency effects that were observed among the frequency responses of the three PSS earphones. It is suggested that one cannot assume equivalent real ear SPLs, with equivalent inputs, among different styles of PSS earphones.

Markers of Hemostatic Activation in Affected Coronary Arteries during Angioplasty

1994 ◽  
Vol 72 (05) ◽  
pp. 672-675 ◽  
Author(s):  
Nicolas W Shammas ◽  
Michael J Cunningham ◽  
Richard M Pomearntz ◽  
Charles W Francis
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Venous Blood ◽  
Balloon Inflation ◽  
Blood Samples ◽  
Hemostatic System ◽  
Significant Difference ◽  
Hemostatic Markers ◽  
Artery Disease ◽  
High Doses

SummaryTo characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrino-peptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation ((3-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.

Rapid Screening Methods for Bleeding Disorders. A Three Year Survey

1964 ◽  
Vol 11 (02) ◽  
pp. 506-512 ◽  
Author(s):  
V. A Lovric ◽  
J Margolis
Keyword(s):  
Laboratory Tests ◽  
Capillary Blood ◽  
Screening Tests ◽  
Rapid Screening ◽  
Screening Methods ◽  
Bleeding Disorders ◽  
Routine Laboratory ◽  
Clotting Time ◽  
Kaolin Clotting Time ◽  
In Infants And Children

SummaryAn adaptation of “kaolin clotting time” and prothrombin time for use on haemolysed capillary blood provided simple and sensitive screening tests suitable for use in infants and children. A survey of three year’s experience shows that these are reliable routine laboratory tests for detection of latent coagulation disorders.

The Ability of Thrombin Inhibitors to Reduce the Thrombin Activity Generated in Plasma on Extrinsic and Intrinsic Activation

1997 ◽  
Vol 77 (03) ◽  
pp. 498-503 ◽  
Author(s):  
D Prasa ◽  
L Svendsen ◽  
J Stürzebecher
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Anion Binding ◽  
Thrombin Inhibitors ◽  
Coagulation System ◽  
Thrombin Activity ◽  
Continuous Registration ◽  
High Concentrations ◽  
20 Nm ◽  
Generation Test

SummaryIn a thrombin generation test with continuous registration of thrombin activity in plasma we studied the ability of a variety of thrombin inhibitors of different type and mechanism of action to influence the activity of thrombin after activation of the coagulation system. Depending on the inhibitor, the peak of thrombin activity is delayed and/or reduced.By blocking the active site of generated thrombin inhibitors cause a concentration dependent reduction of the thrombin peak and inhibit feed-back reactions of thrombin resulting in a delay of thrombin generation. Highly potent synthetic active-site directed inhibitors (Ki ≤ 20 nM) reduce the thrombin activity formed in plasma after extrinsic or intrinsic activation with the same efficiency (IC50 0.1 - 0.6 μM) as hirudin. The delay and reduction of thrombin generation by inhibitors of the anion-binding exosite 1 of thrombin is only attributed to an inhibition of feed-back reactions of thrombin. For a 50% reduction of thrombin activity in plasma by this type of inhibitors relatively high concentrations were determined.

Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

1997 ◽  
Vol 77 (05) ◽  
pp. 0845-0848 ◽  
Author(s):  
B G Koefoed ◽  
C Feddersen ◽  
A L Gulløv ◽  
P Petersen
Keyword(s):  
Atrial Fibrillation ◽  
International Normalized Ratio ◽  
Coagulation System ◽  
Nonvalvular Atrial Fibrillation ◽  
Treatment Groups ◽  
Prothrombin Fragment ◽  
Conventional Dose ◽  
Dose Warfarin ◽  
Significant Difference ◽  
Changes Over Time

SummaryThe efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well- documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 +2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1+2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1+2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in FI +2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1+2.

Levels of Prothrombin Fragment F1+2 in Patients with Hyperhomocysteinemia and a History of Venous Thromboembolism

1997 ◽  
Vol 78 (05) ◽  
pp. 1327-1331 ◽  
Author(s):  
Paul A Kyrle ◽  
Andreas Stümpflen ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
Kurt Herkner ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Thrombin Generation ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Control Group ◽  
Prothrombin Fragment ◽  
Hemostatic System ◽  
Significant Difference ◽  
System Activation ◽  
One Year

SummaryIncreased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment Fl+2 (Fl+2) was determined in the patient’s plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher Fl+2 levels than patients without H-HC (mean 0.52 ± 0.49 nmol/1, median 0.4, range 0.2-2.8, versus 0.36 ± 0.2 nmol/1, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3,6,9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher Fl+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either Fl+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated Fl+2 level(s) followed by recurrent VTE. No statistical significant difference in the Fl+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.

Sign in / Sign up

Export Citation Format

Share Document