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Current Hypertension Reports Oct 2023This review article summarizes the role of coagulation in the pathogenesis of hypertension. It specifically focuses on significant factors and markers associated with... (Review)
Review
PURPOSE OF REVIEW
This review article summarizes the role of coagulation in the pathogenesis of hypertension. It specifically focuses on significant factors and markers associated with coagulation, including D-dimer, fibrinogen and fibrin, prothrombin, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, tissue factor, tissue plasminogen activator, von Willebrand factor, β-thromboglobulin, and Stuart-Prower factor.
RECENT FINDINGS
D-dimer levels were elevated in hypertensive individuals compared to healthy controls, and the levels increased with the severity of hypertension. These findings indicate that increased coagulation activity of fibrin plays a role in the development of thromboembolic complications in hypertensive patients. Additionally, both fibrinogen levels and D-dimer levels displayed a positive correlation with the duration of hypertension, suggesting that these biomarkers were positively associated with the length of time an individual had been hypertensive. Increased systolic and diastolic blood pressures have been linked to higher levels of prothrombin time and activated partial thromboplastin time in individuals with hypertension as well as those with normal blood pressure. Also, the presence of P-selectin, produced by activated platelets and endothelial cells during angiotensin II stimulation, played a role in the development of cardiac inflammation and fibrosis associated with hypertension. Moreover, the change in systolic blood pressure was associated with baseline soluble urokinase plasminogen activator receptor (suPAR) in hypertensive participants, and the change in suPAR levels was associated with the development of hypertension. Moreover, it was observed a decrease in thrombomodulin expression in the placenta of preeclamptic patients, suggesting its potential involvement in placental dysfunction, possibly driven by an imbalance in angiogenic factors. Tissue factors and autophagy might have significant implications in the pathogenesis of chronic thromboembolic pulmonary hypertension, particularly in the context of vascular remodelling. Likewise, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) might be a promising biomarker for the early detection of pulmonary arterial hypertension and the von Willebrand factor is a candidate prognostic biomarker. The arterial β-thromboglobulin levels were significantly lower than venous levels. This article concludes that D-dimer, fibrinogen and fibrin, prothrombin, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, tissue factor, tissue plasminogen activator, von Willebrand factor, and β-thromboglobulin are important factors involved in the pathogenesis of hypertension.
Topics: Humans; Female; Pregnancy; Tissue Plasminogen Activator; Hypertension; Receptors, Urokinase Plasminogen Activator; P-Selectin; Thrombomodulin; beta-Thromboglobulin; Prothrombin; Thromboplastin; von Willebrand Factor; Endothelial Cells; Placenta; Fibrinogen; Biomarkers
PubMed: 37561240
DOI: 10.1007/s11906-023-01258-0 -
Clinical and Molecular Hepatology Apr 2023Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP... (Review)
Review
Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Vitamins; Biomarkers; Prothrombin; Vitamin K; Biomarkers, Tumor
PubMed: 36710606
DOI: 10.3350/cmh.2022.0212 -
Critical Care Medicine Oct 2021To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies.
DATA SOURCES
Embase, Pubmed, Web of Science, and the Cochrane Library.
STUDY SELECTION
Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage.
DATA EXTRACTION
Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event.
DATA SYNTHESIS
A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents.
CONCLUSIONS
Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.
Topics: Coagulants; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Prothrombin; Recombinant Proteins
PubMed: 33967205
DOI: 10.1097/CCM.0000000000005059 -
Thrombosis and Haemostasis Mar 2018This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH) for providing haemostasis-related guidance documents...
This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH) for providing haemostasis-related guidance documents for clinical laboratories. This inaugural coagulation ICSH document was developed by an ad hoc committee, comprised of international clinical and laboratory direct acting oral anticoagulant (DOAC) experts. The committee developed consensus recommendations for laboratory measurement of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban), which would be germane for laboratories assessing DOAC anticoagulation. This guidance document addresses all phases of laboratory DOAC measurements, including pre-analytical (e.g. preferred time sample collection, preferred sample type, sample stability), analytical (gold standard method, screening and quantifying methods) and post analytical (e.g. reporting units, quality assurance). The committee addressed the use and limitations of screening tests such as prothrombin time, activated partial thromboplastin time as well as viscoelastic measurements of clotting blood and point of care methods. Additionally, the committee provided recommendations for the proper validation or verification of performance of laboratory assays prior to implementation for clinical use, and external quality assurance to provide continuous assessment of testing and reporting method.
Topics: Administration, Oral; Anticoagulants; Chromatography; Clinical Laboratory Techniques; Dabigatran; Hematology; Humans; International Cooperation; Mass Spectrometry; Partial Thromboplastin Time; Point-of-Care Testing; Prothrombin; Prothrombin Time; Pyrazoles; Pyridines; Pyridones; Quality Assurance, Health Care; Rivaroxaban; Thiazoles
PubMed: 29433148
DOI: 10.1055/s-0038-1627480 -
Thrombosis and Haemostasis Jul 2022The antiphospholipid syndrome is characterized by antibodies directed against phospholipid-binding proteins and phospholipids attached to cell membrane receptors,...
The antiphospholipid syndrome is characterized by antibodies directed against phospholipid-binding proteins and phospholipids attached to cell membrane receptors, mitochondria, oxidized lipoproteins, and activated complement components. When antibodies bind to these complex antigens, cells are activated and the coagulation and complement cascades are triggered, culminating in thrombotic events and pregnancy morbidity that further define the syndrome. The phospholipid-binding proteins most often involved are annexins II and V, β-glycoprotein I, prothrombin, and cardiolipin. A distinguishing feature of the antiphospholipid syndrome is the "lupus anticoagulant." This is not a single entity but rather a family of antibodies directed against complex antigens consisting of β-glycoprotein I and/or prothrombin bound to an anionic phospholipid. Although these antibodies prolong in vitro clotting times by competing with clotting factors for phospholipid binding sites, they are not associated with clinical bleeding. Rather, they are thrombogenic because they augment thrombin production in vivo by concentrating prothrombin on phospholipid surfaces. Other antiphospholipid antibodies decrease the clot-inhibitory properties of the endothelium and enhance platelet adherence and aggregation. Some are atherogenic because they increase lipid peroxidation by reducing paraoxonase activity, and others impair fetal nutrition by diminishing placental antithrombotic and fibrinolytic activity. This plethora of destructive autoantibodies is currently managed with immunomodulatory agents, but new approaches to treatment might include vaccines against specific autoantigens, blocking the antibodies generated by exposure to cytoplasmic DNA, and selective targeting of aberrant B-cells to reduce or eliminate autoantibody production.
Topics: Antiphospholipid Syndrome; Female; Humans; Lupus Coagulation Inhibitor; Phospholipids; Placenta; Pregnancy; Prothrombin; Thrombosis; beta 2-Glycoprotein I
PubMed: 34794200
DOI: 10.1055/a-1701-2809 -
Thrombosis and Haemostasis Nov 2015Thrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagulable state. Over the past decades,... (Review)
Review
Thrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagulable state. Over the past decades, great advances in the pathogenesis of VTE have been made and nowadays it is well established that a thrombophilic state may be associated with acquired and/or inherited factors. The rare loss-of-function mutations of the genes encoding natural anticoagulant proteins (i. e. protein C, protein S and antithrombin) and the more common gain-of-function polymorphisms factor V Leiden and prothrombin G20210A are the main genetic determinants of thrombophilia. In addition, non-O blood group has been consistently demonstrated to be the most frequent inherited marker of an increased risk of VTE. The mechanism role of these inherited thrombophilia markers will be discussed in this narrative review.
Topics: Animals; Antithrombins; Biomarkers; Factor V; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Prothrombin; Risk Factors; Thrombophilia; Venous Thromboembolism
PubMed: 26018405
DOI: 10.1160/TH15-02-0141 -
Blood Jun 2022The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where the prothrombinase complex, comprising the enzyme factor Xa (fXa), the...
The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where the prothrombinase complex, comprising the enzyme factor Xa (fXa), the cofactor fVa, Ca2+ and phospholipids, activates the zymogen prothrombin to the protease thrombin. The reaction entails cleavage at 2 sites, R271 and R320, generating the intermediates prethrombin 2 and meizothrombin, respectively. The molecular basis of these interactions that are central to hemostasis remains elusive. We solved 2 cryogenic electron microscopy (cryo-EM) structures of the fVa-fXa complex, 1 free on nanodiscs at 5.3-Å resolution and the other bound to prothrombin at near atomic 4.1-Å resolution. In the prothrombin-fVa-fXa complex, the Gla domains of fXa and prothrombin align on a plane with the C1 and C2 domains of fVa for interaction with membranes. Prothrombin and fXa emerge from this plane in curved conformations that bring their protease domains in contact with each other against the A2 domain of fVa. The 672ESTVMATRKMHDRLEPEDEE691 segment of the A2 domain closes on the protease domain of fXa like a lid to fix orientation of the active site. The 696YDYQNRL702 segment binds to prothrombin and establishes the pathway of activation by sequestering R271 against D697 and directing R320 toward the active site of fXa. The cryo-EM structure provides a molecular view of prothrombin activation along the meizothrombin pathway and suggests a mechanism for cleavage at the alternative R271 site. The findings advance our basic knowledge of a key step of coagulation and bear broad relevance to other interactions in the blood.
Topics: Cryoelectron Microscopy; Factor V; Factor Va; Factor Xa; Prothrombin; Thromboplastin
PubMed: 35427420
DOI: 10.1182/blood.2022015807 -
Praxis May 2016Portal vein thrombosis (PVT) is an important, but often delayed or missed differential diagnosis in patients presenting with abdominal pain. In this case report we...
Portal vein thrombosis (PVT) is an important, but often delayed or missed differential diagnosis in patients presenting with abdominal pain. In this case report we present a previously healthy 42-year-old patient with persistent upper abdominal pain for five days. Being a common complication in patients suffering from liver cirrhosis, PVT is an unusual finding in healthy individuals. However, gene mutation leading to a hypercoagulable state can be associated with thrombotic events in the portal venous system. Investigation for underlying disorders such as myeloproliferative neoplasm (MPN), paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid antibody syndrome are crucial.
Topics: Abdominal Pain; Adult; DNA Mutational Analysis; Diagnosis, Differential; Gastroenteritis; Humans; Male; Mesenteric Ischemia; Portal Vein; Prothrombin; Recurrence; Thrombosis; Tomography, X-Ray Computed
PubMed: 27167481
DOI: 10.1024/1661-8157/a002350 -
Blood Jun 2022
Topics: Cryoelectron Microscopy; Factor V; Factor X; Factor Xa; Prothrombin; Thrombin; Thromboplastin
PubMed: 35708725
DOI: 10.1182/blood.2022016537 -
Revista Da Associacao Medica Brasileira... Nov 2020The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose... (Review)
Review
The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these "criteria" of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.
Topics: Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Humans; Prothrombin; Sensitivity and Specificity; beta 2-Glycoprotein I
PubMed: 33295416
DOI: 10.1590/1806-9282.66.11.1595