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.

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.

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.

Acute Pancreatitis in Man and Blood Coagulation Disturbances

1979 ◽  
Author(s):  
H. Kõtering ◽  
M. Hasenbein ◽  
H. Artmann ◽  
U. Kasten ◽  
J. Kellermann
Keyword(s):  
Acute Pancreatitis ◽  
Blood Coagulation ◽  
Thrombin Generation ◽  
The Other ◽  
Phospholipase A ◽  
Coagulation System ◽  
Consumption Coagulopathy ◽  
Blood Coagulation System ◽  
Severe Pancreatitis ◽  
Generation Test

The pathogenesis of blood coagulation-disturbances in patients with acute pancreatitis in man is still unknown. Therefore we studied repeatedly the blood coagulation system of all patients with acute pancreatitis, who were admitted to our clinic or were transferred from other hospitals after complications occurred. 19 patients with a severe pancreatitia were studied. Most of them showed oliguria, pancreatic lungs, thrombosis or haemorrhage. Only 9 determinations (in 5 patients) resulted an enhancement of thrombin generation in the Thrombin-Generation-Test (TGT). All the other patients showed already hypocoagulsbility in the TGT and severe signs of DIC and consumption coagulopathy with a loss of platelets, fibrinogen and prothrombin complex. In 9 patients, who died, we found histomorphologicaliy fibrin deposites and hyaline thrombi. In comparison to 58 patients with elevated amylases but no severe pancreatitiS we found, that the initial alteration of blood coagulation system in pancreatitis is a hypercoagulaoility, possibly caused by trypsin, phospholipase A or elastase.

Zespół rozsianego wykrzepiania wewnątrznaczyniowego w ostrych białaczkach – patofizjologia, obraz kliniczny, diagnostyka oraz leczenie

2018 ◽  
Vol 22 (3) ◽  
Author(s):  
Bartosz Chyżyński ◽  
Barbara Sikorska-Fic ◽  
Edyta Niewiadomska ◽  
Michał Matysiak
Keyword(s):  
Early Diagnosis ◽  
Acute Myeloid Leukaemia ◽  
Acute Leukemia ◽  
Underlying Disease ◽  
Clinical Syndrome ◽  
Coagulation System ◽  
Substitution Treatment ◽  
Substitution Procedure ◽  
Basic Treatment ◽  
Acute Myeloid

Disseminated intravascular coagulation syndrome (DIC) is a syndrome characterized by generalized intravascular activation of the coagulation system. This syndrome is not an isolated clinical syndrome, but is always secondary to other diseases. It is particularly often observed in neoplastic diseases, and in particular in haematopoietic malignancies such as acute leukemia. The risk of DIC depends on the type and subtype of acute leukemia. DIC is most often observed in the course of acute myeloid leukaemia with particular emphasis on the subtype M3 and M5 according to FAB. The basic treatment for DIC remains the treatment of the underlying disease and substitution treatment. Depending on the disease underlying the development of DIC, the substitution procedure may differ significantly. Knowledge of the pathomechanism of disorders occurring in DIC is the key to early diagnosis and rapid implementation of treatment.

scholarly journals Thrombin generation assays and their clinical application

2014 ◽  
Vol 155 (22) ◽  
pp. 851-857 ◽  
Author(s):  
Anita Kern ◽  
Katalin Várnai ◽  
Barna Vásárhelyi
Keyword(s):  
Arterial Thrombosis ◽  
Thrombin Generation ◽  
Coagulation System ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Novel Oral Anticoagulant ◽  
Key Enzyme ◽  
Generation Test ◽  
Bleeding Severity

Thrombin is a key enzyme of the coagulation system, having both pro- and anticoagulant functions. Thus, the generation of thrombin is one of the most important steps in coagulation. Global haemostasis assay, the so-called thrombin generation test is appropriate for its assessment. Since thrombin generation is sensible for both pro- and anticoagulant processes it can be applied for the general characterisation of the risk of thrombosis and bleeding, too. Clinical studies confirmed augmented thrombin generation in patients with high risk of venous or arterial thrombosis. Anticoagulant therapy (also novel oral anticoagulant treatment) can be monitored by thrombin generation. In case of haemophilia thrombin generation assays reflect bleeding severity. It is applicable for monitoring of both conventional haemophilia treatment and inhibitor-bypassing therapy, which is needed when inhibitors develop in patients. Standardization of thrombin generation methods and determination of cut off values are required before its application in clinical practice. Orv. Hetil., 2014, 155(22), 851–857.

Evaluation of Hypercoagulability in Obese Children With Thrombin Generation Test and Microparticle Release: Effect of Metabolic Parameters

2011 ◽  
Vol 17 (6) ◽  
pp. 585-589 ◽  
Author(s):  
Zeynep Şıklar ◽  
Gönül Öçal ◽  
Merih Berberoğlu ◽  
Bülent Hacıhamdioğlu ◽  
Şenay Savas Erdeve ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Thrombin Generation ◽  
Standard Deviation Score ◽  
Metabolic Parameters ◽  
Coagulation System ◽  
Release Time ◽  
Healthy Children ◽  
Obese Children ◽  
Generation Test

Obesity is associated with a hypercoagulable state. Thrombin generation test (TGT) and microparticle levels were not studied in obese children extensively. It is aimed to determine whether any differences in the coagulation system between obese and normal weighed children exist with the use of TGT and microparticles release. A total of 120 obese and 38 healthy children were included to the study. An increase of thrombin generation and microparticles levels were found in obese children. Hyperinsulinism could not find a risk factor for hypercoagulability in our obese children. None of the parameters of TGT has been shown to be related to metabolic parameters and metabolic syndrome. Microparticles release time is found to correlate only to body mass index (BMI) Standard deviation score (SDS) in obese children. Hypercoagulability is associated with childhood obesity. Significant correlation between degree of obesity and microparticles release suggested that high adipokine levels secreted from adipose tissue can stimulate procoagulant status-independent metabolic dearrangements.

Endotoxins And Procqagulant Activities Of Ascitic Fluid

1981 ◽  
Author(s):  
H Murr ◽  
P Schüssler ◽  
G E Rindfleisch ◽  
J Eisenburg ◽  
E Hiller
Keyword(s):  
Ascitic Fluid ◽  
Thrombin Generation ◽  
Procoagulant Activity ◽  
Cirrhosis Of The Liver ◽  
Coagulation System ◽  
Factor X ◽  
Monocytes And Macrophages ◽  
Tissue Thromboplastin ◽  
Generation Test ◽  
Limulus Test

Procoagulant activities in ascitic fluid of patients with cirrhosis of the liver have been reported repeatedly. It has been suggested that they cause DIC after reinfusicn of ascitic fluid, however, the nature of these factors is unknown. Since endotoxins have been found in ascitic fluid and it is known that they can greatly augment the procoagulant activities of monocytes and macrophages, we assayed for the presence of endotoxin and compared the procoagulant activities in each of 15 specimens of ascitic fluid caused either by cirrhosis of the liver or by metastasizing tumors.Endotoxins were assayed by the limulus test. Procoagulant activities were determined by thrcmbelastography, thrombin generation test, the presence of soluble fibrin monomer complexes ( SFMC ) and the ability to activate prothrombin complex and factor X.Endotoxins were detected in 12 of 15 specimens of ascitic fluid caused by cirrhosis of the liver. In 11 of the endotoxin positive and in 2 of the 3 endotoxin negative samples procoagulant activity was present ( i.e. shortened reaction time, increased thrombin generation, activation of prothrombin complex ). In contrast, in only one out of the 15 samples of tumerous ascitic fluid the limulus test was positive. Nevertheless, in 9 of these 15 specimens procoagulant activity was present. In all specimens increased amounts of SFMC were found.The precise mechanism for the activation of the coagulation system following ascitic fluid reinfusion remains to be established. In addition to stimulation of macrophages by endotoxin other factors like tissue thromboplastin release from tumor cells or injured tissues may account for the procoagulant activity of ascitic fluid.

Experimental Studies on a Recombinant Hirudin, CGP 39393

1991 ◽  
Vol 65 (04) ◽  
pp. 355-359 ◽  
Author(s):  
E Gray ◽  
J Watton ◽  
S Cesmeli ◽  
T W Barrowcliffe ◽  
D P Thomas
Keyword(s):  
Thrombin Generation ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Venous Stasis ◽  
Antithrombotic Agent ◽  
Recombinant Hirudin ◽  
Excessive Bleeding ◽  
Generation Test

SummaryThe in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.

scholarly journals POS1199 CLINICAL MANIFESTATIONS OF SARS-CoV2 INFECTIONS IN CHILDREN AND ADOLESCENTS WITH RHEUMATIC AND MUSCULUSKELETAL DISEASES – SURVEY DATA FROM GERMANY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 882.1-882
Author(s):  
C. Sengler ◽  
S. Eulert ◽  
M. Niewerth ◽  
T. Kallinich ◽  
H. Wittkowski ◽  
...  
Keyword(s):  
Disease Activity ◽  
Children And Adolescents ◽  
Symptom Onset ◽  
Clinical Manifestations ◽  
Virus Detection ◽  
German Society ◽  
Underlying Disease ◽  
Common Symptom ◽  
Disease Course ◽  
Cardiorespiratory Failure

Background:Although children and adolescents are less likely to develop COVID-19 and generally show milder disease courses, it is unclear what impact the SARS-CoV2 infection has on children and adolescents with rheumatic and musculoskeletal disease (RMD). Due to their underlying disease as well as therapeutic immunosuppression these patients may be at higher risk of being more severely affected by SARS-CoV2. Furthermore, SARS-CoV2 infection might trigger a flare of the underlying disease.Objectives:To evaluate clinical characteristics and disease course of COVID-19 in children and adolescents with RMD and to analyze possible effects of SARS-CoV2 infection on the underlying disease under different therapeutic regimens.Methods:Data from juvenile patients with RMD recorded via the SARS-CoV2 questionnaire within the National Pediatric Rheumatology Database and the registry for hospitalized children and adolescents with COVID-19 of the German Society for Pediatric Infectious Diseases were analyzed. In addition to age, sex and diagnosis, information was collected about the date and method of a positive SARS-CoV2 testing, reason for testing, on clinical manifestations, disease course, treatment and outcome of COVID-19, on drug therapy at the time of virus detection, on disease activity (NRS 0 – 10, 0 = best) of the underlying disease at the last visit before and after the SARS-CoV2 infection.Results:From April 17th 2020 until January 25th 2021, data of 67 patients with RMD and confirmed SARS-CoV2 infection were collected. Mean age was 13.5 ± 3.9 years with equal sex distribution. The majority of patients were diagnosed with juvenile idiopathic arthritis (JIA, 64%), 12 (18%) patients had an autoinflammatory disease (FMF, CAPS, PFAPA, TRAPS) and 5 (7%) a connective tissue disease. Fifty-two patients (78%) were treated with a disease modifying antirheumatic drug (DMARD), 39% with a biological DMARD and 9% systemic glucocorticoids at the time of SARS-CoV-2 infection. Nineteen patients (28%) were tested for SARS-CoV-2 because of typical symptoms, the majority (67%) because of contact to an infected person. PCR was used most often (in 60 %).52 patients (78%) developed symptoms of COVID-19, 15 patients remained asymptomatic. The most common symptom of COVID-19 was rhinitis (42%) and fever (38%), followed by fatigue (34%), taste/smell disorder (33%), sore throat (27%) and cough (23%).Disease severity was graded as mild in 44 of 52 (85%) symptomatic patients, only two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure 3 days after symptom onset. In 22 of 26 (85%) SARS-CoV2-positive patients, no relevant increase in disease activity (difference in NRS ≤ 1 before/after infection) of the underlying disease was observed 31 days after symptom onset (median, IQR 17-52 days). One patient, who had paused tocilizumab for 2 doses, experienced a flare of his seronegative polyarthritis 2 months after asymptomatic SARS-CoV-2 infection.Conclusion:In our cohort, the clinical picture of COVID-19 in children and adolescents with RMD was similar to that of healthy peers. The majority of patients showed mild disease course with good outcome under various medications, however, one patient with a severe course of COVID-19 died. In addition, SARS-CoV2 infection does not appear to have a relevant impact on the underlying disease activity, whereas discontinuation of therapy might pose a risk of flare.Disclosure of Interests:None declared.

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