Hypercoagulation detected by routine and global laboratory hemostasis assays in patients with infective endocarditis

Background Coagulation system is heavily involved into the process of infective endocarditis (IE) vegetation formation and can facilitate further embolization. In this study we aimed to assess the coagulation and platelet state in IE implementing a wide range of standard and global laboratory assays. We also aim to determine whether prothrombotic genetic polymorphisms play any role in embolization and mortality in IE patients. Methods 37 patients with IE were enrolled into the study. Coagulation was assessed using standard coagulation assays (activated partial thromboplastin time (APTT), prothrombin, fibrinogen, D-dimer concentrations) and integral assays (thromboelastography (TEG) and thrombodynamics (TD)). Platelet functional activity was estimated by flow cytometry. Single nuclear polymorphisms of coagulation system genes were studied. Results Fibrinogen concentration and fibrinogen-dependent parameters of TEG and TD were increased in patients indicating systemic inflammation. In majority of patients clot growth rate in thrombodynamics was significantly shifted towards hypercoagulation in consistency with D-dimers elevation. However, in some patients prothrombin, thromboelastography and thrombodynamics were shifted towards hypocoagulation. Resting platelets were characterized by glycoprotein IIb-IIIa activation and degranulation. In patients with fatal IE, we observed a significant decrease in fibrinogen and thrombodynamics. In patients with embolism, we observed a significant decrease in the TEG R parameter. No association of embolism or mortality with genetic polymorphisms was found in our cohort. Conclusions Our findings suggest that coagulation in patients with infective endocarditis is characterized by general hypercoagulability and platelet pre-activation. Some patients, however, have hypocoagulant coagulation profile, which presumably can indicate progressing of hypercoagulation into consumption coagulopathy.

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Hemostatic abnormalities in dogs with primary immune-mediated hemolytic anemia

Journal of the American Animal Hospital Association ◽

10.5326/15473317-37-3-220 ◽

2001 ◽

Vol 37 (3) ◽

pp. 220-227 ◽

Cited By ~ 90

Author(s):

JC Scott-Moncrieff ◽

NG Treadwell ◽

SM McCullough ◽

MB Brooks

Keyword(s):

Hemolytic Anemia ◽

Disseminated Intravascular Coagulation ◽

Degradation Products ◽

Activated Partial Thromboplastin Time ◽

Common Finding ◽

Fibrinogen Concentration ◽

Immune Mediated ◽

Study Population ◽

Population Mortality ◽

D Dimer

Hemostatic parameters were prospectively measured in 20 dogs with primary immune-mediated hemolytic anemia. Eight of 20 dogs had received prior treatment with prednisone. Activated partial thromboplastin time was increased in nine dogs; one-stage prothrombin time was increased in two dogs; fibrinogen concentration was increased in 17 dogs; and antithrombin activity was decreased in 10 dogs. Fibrin(ogen) degradation products concentration was increased in 12 dogs, and D-dimer concentration was increased in 16 dogs. Four or more laboratory criteria of disseminated intravascular coagulation (DIC) were present in nine dogs, and three criteria of DIC were found in four additional dogs. Thromboembolism was the most common finding in the dogs that died. In this study population, mortality was not significantly associated with any clinical finding or laboratory variable.

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EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2019.01.83-90 ◽

2019 ◽

pp. 83-90

Author(s):

Э.М. Гаглоева ◽

В.Б. Брин ◽

С.В. Скупневский ◽

Н.В. Боциева ◽

Т.В. Молдован

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Enzymes ◽

Platelet Aggregation ◽

Prothrombin Time ◽

Partial Thromboplastin Time ◽

Nickel Chloride ◽

Activated Partial Thromboplastin Time ◽

Fibrinogen Concentration ◽

Thrombin Time ◽

Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

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Prognostic value of D-dimer for adverse outcomes in patients with infective endocarditis: an observational study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02078-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying-Wen Lin ◽

Mei Jiang ◽

Xue-biao Wei ◽

Jie-leng Huang ◽

Zedazhong Su ◽

...

Keyword(s):

Regression Analysis ◽

Infective Endocarditis ◽

Adverse Events ◽

Prognostic Value ◽

Multivariable Analysis ◽

Adverse Outcomes ◽

Hospital Death ◽

Large Sample Size ◽

Cox Regression Analysis ◽

D Dimer

Abstract Background Increased D-dimer levels have been shown to correlate with adverse outcomes in various clinical conditions. However, few studies with a large sample size have been performed thus far to evaluate the prognostic value of D-dimer in patients with infective endocarditis (IE). Methods 613 patients with IE were included in the study and categorized into two groups according to the cut-off of D-dimer determined by receiver operating characteristic (ROC) curve analysis for in-hospital death: > 3.5 mg/L (n = 89) and ≤ 3.5 mg/L (n = 524). Multivariable regression analysis was used to determine the association of D-dimer with in-hospital adverse events and six-month death. Results In-hospital death (22.5% vs. 7.3%), embolism (33.7% vs 18.2%), and stroke (29.2% vs 15.8%) were significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L. Multivariable analysis showed that D-dimer was an independent risk factor for in-hospital adverse events (odds ratio = 1.11, 95% CI 1.03–1.19, P = 0.005). In addition, the Kaplan–Meier curve showed that the cumulative 6-month mortality was significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L (log-rank test = 39.19, P < 0.0001). Multivariable Cox regression analysis showed that D-dimer remained a significant predictor for six-month death (HR 1.11, 95% CI 1.05–1.18, P < 0.001). Conclusions D-dimer is a reliable prognostic biomarker that independently associated with in-hospital adverse events and six-month mortality in patients with IE.

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Screening Coagulation Assays, Factor XIII and D-dimer

Management of Bleeding Patients ◽

10.1007/978-3-030-56338-7_2 ◽

2021 ◽

pp. 11-23

Author(s):

Dorothy M. Adcock ◽

Brian F. Poirier

Keyword(s):

Factor Xiii ◽

Coagulation Assays ◽

D Dimer

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ASSESSMENT OF COAGULATION PROFILE IN PATIENTS WITH LIVER CIRRHOSIS AND ATRIAL FIBRILLATION

Ukrainian Scientific Medical Youth Journal ◽

10.32345/usmyj.1(121).2021.22-31 ◽

2021 ◽

Vol 121 (1) ◽

pp. 22-31

Author(s):

Alіna Baylo ◽

Vadym Shypulіn ◽

Volodymyr Chernyavskyi ◽

Luiza Parunyan

Keyword(s):

Atrial Fibrillation ◽

Liver Cirrhosis ◽

Prothrombin Time ◽

Partial Thromboplastin Time ◽

International Normalized Ratio ◽

Activated Partial Thromboplastin Time ◽

Fibrinolytic System ◽

Thrombin Time ◽

Group I ◽

D Dimer

The comorbid course of liver cirrhosis and atrial fibrillation causes higher levels of hospitalizations, mortality and ischemic stroke. According to current data, hemostasis in patients with liver cirrhosis is in a rebalanced dynamic state, but there are no data on the effect of atrial fibrillation on the hemostasis in patients with liver cirrhosis. Aims of the study. To assess abnormalities in primary, secondary haemostasis and fibrinolytic system in patients with liver cirrhosis and atrial fibrillation by using standard laboratory coagulation parameters and to investigate their changes depending on the stage of liver cirrhosis A, B, C according to Child-Pugh score. Materials and methods. A cross-sectional prospective study was conducted with the inclusion of 106 patients aged 42 to 83 years: group I (n = 70) - with liver cirrhosis and atrial fibrillation, II (n = 36) - with liver cirrhosis, which were distributed depending on the Child-Pugh score stages of cirrhosis and 20 healthy individuals. The levels of platelets, activated partial thromboplastin time, international normalized ratio, prothrombin time, thrombin time, fibrinogen, D-dimer were assessed on a Steellex M200 coagulometer. Statistical analysis (IBM SPSS Statistics) was performed. Results. The level of platelets in patients of group I was reduced by 37.4% (200 ± 8.33 vs. 274.7 ± 3.4; p,000.001), an activated partial thromboplastin time was prolonged by 38.6% (44.35 ± 1.39 vs. 32.01 ± 0.63, p˂0.001), prothrombin time was prolonged by 73.5% (19.4 ± 0.87 vs. 11.18 ± 0.53, p˂0.001), thrombin time was prolonged by 2.07 (25, 7 ± 1.31 vs. 12.4 ± 0.66, p˂0.001), the international normalized ratio was increased by 24.3% (1.38 ± 0.04 vs.1.11 ± 0.01, p˂0.001) compared to control. The fibrinogen level was 20.9% higher (4.17 ± 0.17 vs. 3.45 ± 0.11, p˂0.001) than in control group and was 83.7% higher (4.17 ± 0.17 vs. 2.27 ± 0.13, p˂0.001) than in group II. The D-dimer level was 83% higher than in control (675 ± 22.3 vs. 368.8 ± 21.85, p˂0.001) and 44% higher (675 ± 22.3 vs. 469 ± 37.18, p ˂0.001) compared with group II. Conclusions. In patients with liver cirrhosis and atrial fibrillation abnormalities of primary hemostasis are detected due to decrease of platelets on the background of portal hypertension. At the secondary stage of hemostasis indicators of external and internal coagulation mechanisms are prolonged due to the reduced synthesis of coagulation factors by the liver. Increased level of fibrinogen is determined at the stage of compensated and subcompensated cirrhosis with a gradual decrease at the stage of decompensation. The high activity of the fibrinolytic system is observed due to increase in the D-dimer levels, which may indicate a prothrombotic state in these patients.

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Screening Coagulation Assays, Factor XIII and D-Dimer

Management of Bleeding Patients ◽

10.1007/978-3-319-30726-8_1 ◽

2016 ◽

pp. 3-16

Author(s):

Dorothy M. Adcock ◽

Brian F. Poirier

Keyword(s):

Factor Xiii ◽

Coagulation Assays ◽

D Dimer

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Reference Values of D-Dimers and Fibrinogen in the Course of Physiological Pregnancy: the Potential Impact of Selected Risk Factors—A Pilot Study

BioMed Research International ◽

10.1155/2020/3192350 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Aldona Siennicka ◽

Magdalena Kłysz ◽

Kornel Chełstowski ◽

Aleksandra Tabaczniuk ◽

Zuzanna Marcinowska ◽

...

Keyword(s):

Risk Factors ◽

Gestational Diabetes ◽

Reference Values ◽

Venous Blood ◽

Fibrinogen Concentration ◽

Reference Ranges ◽

Second Trimester ◽

Increase Risk ◽

Potential Impact ◽

D Dimer

Pregnancy predisposes to thrombotic hemostasis, reflected in the laboratory as, e.g., increased levels of D-Dimers and fibrinogen, but in physiological pregnancy, the risk of venous thrombosis does not increase. Risk may increase if gestational diabetes mellitus (GDM) or nicotinism coexists. Study aims were to determine reference values for D-Dimers and fibrinogen concentrations in each trimester of pregnancy, corrected for GDM and nicotinism. Subjects and Methods. The study involved 71 pregnant women aged 25-44 y. Venous blood was collected three times: in the first (11-14 weeks), second (20-22 weeks), and third (30-31 weeks) trimesters. D-Dimer concentrations were determined by an enzyme-linked fluorescence assay, fibrinogen concentrations by a coagulation method according to Clauss. Results. Significant increases in D-Dimers and fibrinogen concentrations were observed, increasing with successive trimesters (p ANOVA<0.0001). Furthermore, a positive correlation between D-Dimers and fibrinogen was detected in the second trimester of pregnancy (r=0.475; p<0.0001). In addition, a significantly higher fibrinogen concentration was found in women with GDM compared to without GDM (p=0.0449). Reference ranges for D-Dimers were established, in trimester order, as follows: 167-721 ng/mL, 298-1653 ng/mL, and 483-2256 ng/mL. After adjusting for risk factors, significantly higher D-Dimer values (mainly second and third trimesters) were obtained: 165-638 ng/mL, 282-3474 ng/mL, and 483-4486 ng/mL, respectively. Reference ranges for fibrinogen were, in trimester order, 2.60-6.56 g/L, 3.40-8.53 g/L, and 3.63-9.14 g/L and, after adjustment for risk factors, 3.34-6.73 g/L, 3.40-8.84 g/L, and 3.12-9.91 g/L. Conclusions. We conclude that the increase in D-Dimers and fibrinogen levels in women with physiological pregnancy was compounded by gestational diabetes (GDM) and nicotinism. Therefore, D-Dimers and fibrinogen pregnancy reference values require correction for these risk factors.

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Compensated activation of coagulation in patients with abdominal aortic aneurysm: effects of heparin treatment prior to elective surgery

Thrombosis and Haemostasis ◽

10.1160/th03-10-0665 ◽

2004 ◽

Vol 92 (11) ◽

pp. 997-1002 ◽

Cited By ~ 14

Author(s):

Jacek Szmidt ◽

Krzystof Bojakowski ◽

Tomasz Grzela ◽

Magorzata Palester-Chlebowczyk ◽

Maria Jelenska

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Reference Group ◽

Elective Surgery ◽

Operation Time ◽

Fibrinogen Concentration ◽

Excessive Bleeding ◽

Prothrombin Fragment ◽

Abdominal Aortic ◽

D Dimer

SummaryElective surgery of abdominal aortic aneurysm (AAA) sometimes leads to excessive bleeding and disseminated intravascular coagulation (DIC), even in patients with normal preoperative coagulation parameters. Coagulation screen, performed routinely before surgery is of limited value in the assessment of compensated activation of the haemostatic system. In this study, we used a number of additional tests (D-dimer, prothrombin fragment 1+2, antithrombin, and activation of fibrinolysis in the platelet poor plasma) for the diagnosis of compensated activation of the haemostatic system in AAA-patients. Ddimer and marker of thrombin generation (prothrombin fragment 1+2) positively correlated with each other (r = 0.768, P < 0.001). Out of 71 AAA patients, 15 patients had normal global coagulation times, but those with a Ddimer concentration above 3000 ng/ml were selected for preoperative low molecular weight heparin (LMWH) treatment. Administration of LMWH diminished coagulation abnormalities (D-dimer and prothrombin fragment 1+2 decreased significantly) and resulted in the increase of platelet number and fibrinogen concentration, indicating their previous consumption. Despite differences in aneurysm diameters between the groups of 15 LMWH treated patients (mean 70.9 ± 16 mm) and the reference group of 20 untreated AAA patients (mean 52.3 ± 8.0 mm), intraoperative parameters (operation time, blood loss and transfusion demands) were similar.

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Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite

Toxins ◽

10.3390/toxins12090583 ◽

2020 ◽

Vol 12 (9) ◽

pp. 583 ◽

Cited By ~ 2

Author(s):

Supun Wedasingha ◽

Geoffrey Isbister ◽

Anjana Silva

Keyword(s):

Low Income ◽

Whole Blood ◽

Blood Clotting ◽

Specific Treatment ◽

Small Sample ◽

Consumption Coagulopathy ◽

Clotting Time ◽

Wide Range ◽

Coagulation Tests ◽

Blood Clotting Time

Venom-induced consumption coagulopathy is the most important systemic effect of snake envenoming. Coagulation tests are helpful to accurately and promptly diagnose venom-induced consumption coagulopathy and administer antivenom, which is the only specific treatment available. However, bedside clotting tests play a major role in diagnosing coagulopathy in low-income settings, where the majority of snakebites occur. We conducted a literature search in MEDLINE® from 1946 to 30 November 2019, looking for research articles describing clinical studies on bedside coagulation tests in snakebite patients. Out of 442 articles identified, 147 articles describing bedside clotting assays were included in the review. Three main bedside clotting tests were identified, namely the Lee–White clotting test, 20-min whole blood clotting time and venous clotting time. Although the original Lee–White clotting test has never been validated for snake envenoming, a recently validated version has been used in some South American countries. The 20-min whole blood clotting time test is the most commonly used test in a wide range of settings and for taxonomically diverse snake species. Venous clotting time is almost exclusively used in Thailand. Many validation studies have methodological limitations, including small sample size, lack of case-authentication, the inclusion of a heterogeneous mix of snakebites and inappropriate uses of gold standard tests. The observation times for bedside clotting tests were arbitrary, without proper scientific justification. Future research needs to focus on improving the existing 20-min whole blood clotting test, and also on looking for alternative bedside coagulation tests which are cheap, reliable and quicker.

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