scholarly journals Coagulation Inhibitors in COVID-19 Leading to Compressive Airway Hematoma

Cureus ◽  
2021 ◽  
Author(s):  
Amr Mohamed
Keyword(s):  
Coagulation Inhibitors

Extrinsic Pathway Inhibitor in Elective Surgery: A Comparison with other Coagulation Inhibitors

1989 ◽  
Vol 62 (03) ◽  
pp. 856-860 ◽  
Author(s):  
P M Sandset ◽  
H E Høgevold ◽  
T Lyberg ◽  
T R Andersson ◽  
U Abildgaard
Keyword(s):  
Vascular Surgery ◽  
Protein C ◽  
Elective Surgery ◽  
Perioperative Period ◽  
Acute Phase Reactant ◽  
Hip Surgery ◽  
Albumin Concentration ◽  
Extrinsic Pathway ◽  
Heparin Cofactor Ii ◽  
Coagulation Inhibitors

SummaryExtrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of anti thrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution.

The 536C→T Transition in the Human Tissue Factor Pathway Inhibitor (TFPI) Gene Is Statistically Associated with a Higher Risk for Venous Thrombosis

1999 ◽  
Vol 82 (07) ◽  
pp. 1-5 ◽  
Author(s):  
Michael Schmidt ◽  
Christian Götting ◽  
Britt Schwenz ◽  
Stefan Lange ◽  
Gert Müller-Berghaus ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Blood Donors ◽  
Amino Acid Position ◽  
Immunological Methods ◽  
Venous Thromboembolic ◽  
Coagulation Inhibitors ◽  
Tissue Factor Pathway

SummaryTissue factor pathway inhibitor (TFPI) is an important regulator in the extrinsic blood coagulation pathway. Although the regulatory biochemical role of TFPI is evident, the clinical significance of this proteinase inhibitor remains to be elucidated. The definition of a clinical TFPI deficiency seems to be more complex than that of other coagulation inhibitors because the activity and concentration of circulating TFPI can not be considered a true measure of in vivo levels. Its determination in plasma samples by immunological methods or functional assays has been shown to be inadequate in the detection of a clinical deficiency.Therefore, we screened genomic DNA samples of blood donors and thrombotic patients for alterations in the TFPI gene to assess the influence of a modified TFPI in venous thromboembolic diseases. We detected a single nucleotide substitution in exon 7 (536C→T) leading to a proline to leucine exchange at amino acid position 151 of the protein ([P151L]TFPI) and found the prevalence of heterozygous carriers in German unrelated blood donors to be 0.2% (n = 5120).Four unrelated persons out of 14 probands carrying the genetic variation could be linked to venous thrombosis. For calculation of a potential risk for venous thrombosis for carriers of the mutation we investigated healthy blood donors about thrombotic events. 7 out of 308 blood donors were found to have a history of venous thrombosis, one of them carried the TFPI mutation. Statistical calculation showed a significant relative risk for venous thrombosis for individuals with the trait (odds ratio, 9.3; confidence interval, 1.8-48.6; p <0.01).

scholarly journals Targeting exosites on blood coagulation proteases

2005 ◽  
Vol 77 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Robson Q. Monteiro
Keyword(s):  
Blood Coagulation ◽  
High Specificity ◽  
Heparin Binding ◽  
Zymogen Activation ◽  
Prothrombinase Complex ◽  
Blood Sucking ◽  
Anticoagulant Drugs ◽  
Coagulation Inhibitors ◽  
Tissue Factor Pathway ◽  
Surface Domains

The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed in this short revision. Bothrojaracin is a snake venom-derived protein that binds to thrombin exosites 1 and 2. Complex formation impairs several exosite-dependent activities of thrombin including fibrinogen cleavage and platelet activation. Bothrojaracin also interacts with proexosite 1 on prothrombin thus decreasing the zymogen activation by the prothrombinase complex (FXa/FVa). Ixolaris is a two Kunitz tick salivary gland inhibitor, that is homologous to tissue factor pathway inhibitor. Recently it was demonstrated that ixolaris binds to heparin-binding exosite of FXa, thus impairing the recognition of prothrombin by the enzyme. In addition, ixolaris interacts with FX possibly through the heparin-binding proexosite. Differently from FX, the ixolaris-FX complex is not recognized as substrate by the intrinsic tenase complex (FIXa/FVIIIa). We conclude that these inhibitors may serve as tools for the study of coagulation exosites as well as prototypes for new anticoagulant drugs.

scholarly journals Etiology of ischemic stroke among young adults of Serbia

2008 ◽  
Vol 65 (11) ◽  
pp. 803-809 ◽  
Author(s):  
Dejana Jovanovic ◽  
Ljiljana Beslac-Bumbasirevic ◽  
Ranko Raicevic ◽  
Jasna Zidverc-Trajkovic ◽  
Marko Ercegovac
Keyword(s):  
Risk Factors ◽  
Young Adults ◽  
Ischemic Stroke ◽  
Heart Diseases ◽  
Developed Countries ◽  
Large Artery ◽  
Stroke Treatment ◽  
Prosthetic Valves ◽  
Number Of Patients ◽  
Coagulation Inhibitors

Background/Aim. Etiology of ischemic stroke (IS) among young adults varies among countries. The aim of the study was to investigate the causes and risk factors of IS in the young adults of Serbia. Methods. A total of 865 patients with IS, aged 15 to 45 years, were treated throughout the period 1989-2005. Etiologic diagnostic tests were performed on the patient by the patient basis and according to their availability at the time of investigation. The most likely cause of stroke was categorized according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. Results. There were 486 men and 379 women, with 19% of the patients ? 30 years old. Large artery arteriosclerosis and small artery disease were confirmed in 14% of the patients, and embolism and other determined causes in 20%. Undetermined causes made up 32% of the patients, mostly those (26%) with incomplete investigations. Smoking (37%), hypertension (35%) and hyperlipidemia (35%) were the most common risk factors. Rheumatic heart diseases and prosthetic valves were the most common causes of IS. Arterial dissections and coagulation inhibitors deficiency were detected in a small number of patients. Conclusion. Etiology of IS among Serbian young adults shares characteristics of those in both western and less developed countries.

scholarly journals Neutralizing and Non-Neutralizing Anti-FVIII Antibodies in Black and White Hemophilia A Subjects: A Natural History Profile

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1131-1131 ◽  
Author(s):  
Kathleen P. Pratt ◽  
Devi Gunasekera ◽  
Pooja Vir ◽  
Robert Peters ◽  
Siyuan Tan ◽  
...  
Keyword(s):  
B Cell ◽  
Hemophilia A ◽  
African Ancestry ◽  
Full Length ◽  
Inhibitory Antibody ◽  
B Cell Epitopes ◽  
Black African ◽  
Coagulation Inhibitors ◽  
Antibody Titers ◽  
Linear B

The most common complication in hemophilia A (HA) treatment, affecting 25-30% of severe HA patients, is the development of alloimmune inhibitors that foreclose the ability of infused factor VIII (FVIII) to participate in coagulation. Inhibitors confer significant pathology on affected individuals and present major complexities in their management. Inhibitors are more common in African American patients, and it has been hypothesized that this is a consequence of haplotype (H)-treatment product mismatch. F8 gene haplotypes H1-H5 are defined by combinations of nonsynonymous SNPs encoding FVIII sequence variants D1241E, M2238V and R484H. F8 haplotypes H2-H5 are more prevalent in individuals with black African ancestry, while >90% of the white population has the H1 haplotype. This study used a validated Luminex-based assay to determine total anti-FVIII antibody titers in plasma from 395 HA (189 black, 206 white) and 23 non-HA control subjects, measuring their binding to recombinant full-length H1 and H2 and B-domain-deleted (BDD) H1/H2, H3 and H4 FVIII proteins. Inhibitor titers were determined using a chromogenic Bethesda assay with the Nijmegen modification. Linear B-cell epitopes recognized by antibodies in human plasma samples were characterized using commercial peptide microarrays with imprinted 15-mer peptides spanning the FVIII A1, A2, C1 and C2 domains, with binding interactions detected using fluorescent-labeled anti-human IgG antibodies. Neither total nor inhibitory antibody titers correlated with F8 haplotype. FVIII peptides with the D1241E and M3348V polymorphisms showed low antibody reactivity, indicating they do not comprise linear B-cell epitopes. Similarly, antibodies from subjects with H3 and H5 haplotypes, who were necessarily infused with FVIII products having a different haplotype than that of their endogenous, (dysfunctional) F8 sequence, did not show haplotype-correlated differential binding to the three BDD-FVIII or full-length FVIII proteins, indicating the polymorphic M2238V or D1241E sites do not correspond to immunodominant, conformational B-cell epitopes. Interestingly, the BDD-FVIII proteins were significantly more reactive with antibodies in plasma than were two commercial full-length recombinant FVIII products. Overall, results of this study indicated that low-titer FVIII-reactive antibodies are readily detected in most HA subjects and in a majority of healthy non-HA controls. The observed stronger immunoreactivity of BDD-FVIII suggests that B-domain removal exposes novel B-cell epitopes, perhaps through conformational rearrangements of FVIII domains. Disclosures Pratt: Bloodworks NW: Patents & Royalties: inventor on patents related to FVIII immunogenicity; Grifols, Inc: Research Funding. Peters:Sanofi: Employment. Mann:Haematologic Technologies: Other: Owner; Stago: Consultancy; Novo Nordisk: Consultancy; Takeda: Consultancy; Shire: Consultancy; Baxalta: Consultancy.

scholarly journals Elevated levels of tissue factor pathway inhibitor in patients with mild to moderate bleeding tendency

2021 ◽  
Vol 5 (2) ◽  
pp. 391-398
Author(s):  
Dino Mehic ◽  
Alexander Tolios ◽  
Stefanie Hofer ◽  
Cihan Ay ◽  
Helmuth Haslacher ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Genetic Alterations ◽  
Factor V ◽  
Bleeding Tendency ◽  
Healthy Controls ◽  
Single Nucleotide ◽  
Time To Peak ◽  
Coagulation Inhibitors ◽  
Tissue Factor Pathway

Abstract High levels of tissue factor pathway inhibitor (TFPI), caused by a longer TFPIα half-life after binding to a factor V splice variant and variants in the F5 gene, were recently identified in 2 families with an as-yet-unexplained bleeding tendency. This study aimed to investigate free TFPIα in a well-characterized cohort of 620 patients with mild to moderate bleeding tendencies and its association to genetic alterations in the F5 gene. TFPIα levels were higher in patients with bleeding compared with healthy controls (median [interquartile range], 8.2 [5.5-11.7] vs 7.8 [4.3-11.1]; P = .026). A higher proportion of patients had free TFPIα levels more than or equal to the 95th percentile compared with healthy controls (odds ratio [OR] [95% confidence interval (CI)], 2.82 [0.98-8.13]). This was pronounced in the subgroup of patients in whom no bleeding disorder could be identified (bleeding of unknown cause [BUC; n = 420]; OR [95% CI], 3.03 [1.02-8.98]) and in platelet function defects (PFDs) (n = 121; OR [95% CI], 3.47 [1.09-11.08]). An increase in free TFPIα was associated with a mild delay in thrombin generation (prolonged lag time and time to peak), but not with alterations in routinely used global clotting tests. We could neither identify new or known genetic variations in the F5 gene that are associated with free TFPIα levels, nor an influence of the single-nucleotide variant rs10800453 on free TFPIα levels in our patient cohort. An imbalance of natural coagulation inhibitors such as TFPIα could be an underlying cause or contributor for unexplained bleeding, which is most probably multifactorial in a majority of patients.

New biological concepts on coagulation inhibitors

1993 ◽  
Vol 19 (S1) ◽  
pp. S3-S7 ◽  
Author(s):  
N. Sala ◽  
J. Fontcuberta ◽  
M. LL. Rutllant
Keyword(s):  
Coagulation Inhibitors ◽  
Biological Concepts

BIOLOGICAL PRETHROMBOTIC MARKERS AND COAGULATION INHIBITORS IN NEPHROTIC SYNDROME

1987 ◽  
Author(s):  
P Picard ◽  
J Y Borg ◽  
M Vasse ◽  
D Boudhabhay ◽  
J Soria ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Acute Phase Proteins ◽  
Degradation Products ◽  
Protein S ◽  
Factor Vii ◽  
Activated Factor Vii ◽  
Prethrombotic State ◽  
At Iii ◽  
Coagulation Inhibitors

Nephrotic syndrome (NS) has long been recognized as a clinical prethrombotic state, because of severe thrombo-embolic complications. But underlying mechanisms are still poorly defined. In 56 untreated nephrotic adult patients (most of them without renal failure), we investigate in vivo coagulation activation by measuring 0 plasmatic specific fibrin degradation products (FbDP) (immuno-enzymological assay using a monoclonal anti D-neo antibody) and (2) the ratio of factor VII coagulant activity (V11c) to factor VII:Anti gen (VII;Ag) tested by an ELISA method. We examined coagulation inhibitors in plasmas and urines (antithrombin III—AT III, heparin cofactor II-HC II by amidolytic and laurell methods; protein C-PC by an ELISA assay ;free and bound protein S—PS:Ag by laurell assays). In few patients we also determinecjfribronectin and t-PA inhibitor.Results in plasma are submitted and expressed as mean ± DS and compared (t test) with controls (C) without nephropathySignificantly elevated activated factor VII and FbDP levels show an “in vivo activation” of coagulation in NS. Plasmatic fibronectin, HC II, PC:frg, and tPA-I levels are alsp significantly elevated and roughly paralleled fibrinogen (6,25 ± 2,9 g/1) and other acute-phase proteins measurements. Significant amounts of AT 111:Ag were present in about half tested urines, but in a degraded form with low or absent heparin cofactor activity. Mean plasmatic AT III concentration was in normal range, but three of the 4 patients with a thrombotic disease had the lowest values of AT III and the highest fibrinogen levels.We could demonstrate a biological prethrombotic state in NS and suggest the way of identifying patients with high risk of thrombosis.

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