Faculty Opinions recommendation of Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data.

2015 ◽  
Author(s):  
Toshiyuki Miyata
Keyword(s):  
Venous Thrombosis ◽  
Factor Xa ◽  
Metabolomics Data ◽  
Inhibit Factor

scholarly journals Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data

Blood ◽  
2015 ◽  
Vol 126 (13) ◽  
pp. 1595-1600 ◽  
Author(s):  
Hiroshi Deguchi ◽  
Yajnavalka Banerjee ◽  
Sunia Trauger ◽  
Gary Siuzdak ◽  
Ewa Kalisiak ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Glutamic Acid ◽  
Factor Xa ◽  
Targeted Metabolomics ◽  
Metabolomics Data ◽  
Thrombosis Risk ◽  
Key Points ◽  
Acid Domain ◽  
Long Chain ◽  
Inhibit Factor

Key PointsUntargeted and targeted metabolomics showed association of low plasma acylcarnitines levels with venous thrombosis risk. Long-chain acylcarnitines are anticoagulants that inhibit factor Xa by binding to factor Xa outside the γ-carboxy glutamic acid domain.

scholarly journals Heparin cofactor activities in a family with hereditary antithrombin III deficiency: evidence for a second heparin cofactor in human plasma

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 111-118 ◽  
Author(s):  
MJ Griffith ◽  
T Carraway ◽  
GC White ◽  
FA Dombrose
Keyword(s):  
Venous Thrombosis ◽  
Affinity Chromatography ◽  
Human Plasma ◽  
Functional Properties ◽  
Plasma Levels ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Normal Plasma ◽  
Antithrombin Iii Deficiency ◽  
Inhibit Factor

Abstract Plasma levels of antithrombin-heparin cofactor, determined by heparin- dependent antithrombin assay, and antithrombin III antigen were measured in 22 members of a large kindred predisposed to venous thrombosis. While 11 members had reduced plasma levels of both antithrombin-heparin cofactor and antithrombin III antigen, the levels of antithrombin-heparin cofactor were always greater than the levels of antithrombin III antigen: 66% (+/- 7%) and 49% (+/- 5%) of normal plasma, respectively. Pooled normal plasma and plasma from one of the affected family members (60% antithrombin-heparin cofactor and 47% antithrombin III antigen) were fractionated by heparin-agarose affinity chromatography. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 0.4 M NaCl and did not cross- react with antibody specific for antithrombin III and did not inhibit factor Xa at an appreciable rate in the presence of heparin, was designated heparin cofactor A. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 2.0 M NaCl, was functionally and antigenically identified as antithrombin III. The concentrations of heparin cofactor A in normal and patient plasma were similar (4.5 x 10(-7) M), while the concentration of antithrombin III in patient plasma (8.0 x 10(-7) M) was only 50% of normal (1.6 x 10(-6) M). The functional properties of both heparin cofactor A and antithrombin III obtained from patient plasma were normal. From the results of the present study it would appear that the antithrombin- heparin cofactor concentrating measured in patient plasma reflects the combined concentrations of heparin cofactor A and antithrombin III. Since heparin cofactor A does not cross-react with antibody to antithrombin III, the concentration of antithrombin III antigen in patient plasma is thus lower than the concentration of antithrombin- heparin cofactor.

scholarly journals Heparin cofactor activities in a family with hereditary antithrombin III deficiency: evidence for a second heparin cofactor in human plasma

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 111-118
Author(s):  
MJ Griffith ◽  
T Carraway ◽  
GC White ◽  
FA Dombrose
Keyword(s):  
Venous Thrombosis ◽  
Affinity Chromatography ◽  
Human Plasma ◽  
Functional Properties ◽  
Plasma Levels ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Normal Plasma ◽  
Antithrombin Iii Deficiency ◽  
Inhibit Factor

Plasma levels of antithrombin-heparin cofactor, determined by heparin- dependent antithrombin assay, and antithrombin III antigen were measured in 22 members of a large kindred predisposed to venous thrombosis. While 11 members had reduced plasma levels of both antithrombin-heparin cofactor and antithrombin III antigen, the levels of antithrombin-heparin cofactor were always greater than the levels of antithrombin III antigen: 66% (+/- 7%) and 49% (+/- 5%) of normal plasma, respectively. Pooled normal plasma and plasma from one of the affected family members (60% antithrombin-heparin cofactor and 47% antithrombin III antigen) were fractionated by heparin-agarose affinity chromatography. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 0.4 M NaCl and did not cross- react with antibody specific for antithrombin III and did not inhibit factor Xa at an appreciable rate in the presence of heparin, was designated heparin cofactor A. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 2.0 M NaCl, was functionally and antigenically identified as antithrombin III. The concentrations of heparin cofactor A in normal and patient plasma were similar (4.5 x 10(-7) M), while the concentration of antithrombin III in patient plasma (8.0 x 10(-7) M) was only 50% of normal (1.6 x 10(-6) M). The functional properties of both heparin cofactor A and antithrombin III obtained from patient plasma were normal. From the results of the present study it would appear that the antithrombin- heparin cofactor concentrating measured in patient plasma reflects the combined concentrations of heparin cofactor A and antithrombin III. Since heparin cofactor A does not cross-react with antibody to antithrombin III, the concentration of antithrombin III antigen in patient plasma is thus lower than the concentration of antithrombin- heparin cofactor.

Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dose Adaptation ◽  
Heparin Treatment ◽  
Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

scholarly journals Unfractionated heparin inhibits thrombin-catalysed amplification reactions of coagulation more efficiently than those catalysed by factor Xa

1989 ◽  
Vol 257 (1) ◽  
pp. 143-150 ◽  
Author(s):  
F A Ofosu ◽  
J Hirsh ◽  
C T Esmon ◽  
G J Modi ◽  
L M Smith ◽  
...  
Keyword(s):  
Factor Viii ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Activate Factor ◽  
Factor V ◽  
Inhibitory Effects ◽  
Exogenous Factor ◽  
Additional Support ◽  
Prothrombin Activation ◽  
Inhibit Factor

We have proposed previously that the steps in coagulation most sensitive to inhibition by heparin are the thrombin-dependent amplification reactions, and that prothrombinase is formed in heparinized plasma only after Factor Xa activates Factor VIII and Factor V. These propositions were based on the demonstration that both heparin and Phe-Pro-Arg-CH2Cl completely inhibited 125I-prothrombin activation for up to 60 s when contact-activated plasma (CAP) was replenished with Ca2+. Furthermore, the addition of thrombin to CAP before heparin or Phe-Pro-Arg-CH2Cl completely reversed their inhibitory effects. Additional support for the above hypotheses is provided in this study by demonstrating that, when the activity of thrombin is suppressed by heparin (indirectly) or by Phe-Pro-Arg-CH2Cl (directly), exogenous Factor Xa reverses the ability of these two agents to inhibit prothrombin activation. Prothrombin activation was initiated by adding Factor Xa (1 nM) or thrombin (1 or 10 nM) simultaneously with CaCl2 to CAP. In the absence of heparin or Phe-Pro-Arg-CH2Cl, prothrombin activation was seen 15 s later in either case. Heparin failed to delay, and Phe-Pro-Arg-CH2Cl delayed for 15 s, prothrombin activation in CAP supplemented with Factor Xa. In contrast, heparin and Phe-Pro-Arg-CH2Cl completely inhibited prothrombin activation for at least 45 s in CAP supplemented with 1 nM-thrombin. Heparin failed to delay prothrombin activation in CAP supplemented with 10 nM-thrombin, whereas Phe-Pro-Arg-CH2Cl completely inhibited prothrombin activation in this plasma for 45 s. These results suggest that in CAP: (1) Factor Xa can effectively activate Factor VIII and Factor V when the proteolytic activity of thrombin is suppressed; (2) heparin-antithrombin III is less able to inhibit Factor Xa than thrombin; (3) suppression of the thrombin-dependent amplification reactions is the primary anticoagulant effect of heparin.

Modifications of Extrinsic Pathway Inhibitor (EPI) and Factor Xa that Affect their Ability to Interact and to Inhibit Factor Vila/Tissue Factor: Evidence for a Two-Step Model of Inhibition

1988 ◽  
Vol 60 (03) ◽  
pp. 453-456 ◽  
Author(s):  
Bonnie J Warn-Cramer ◽  
L Vijaya Mohan Rao ◽  
Steven L Maki ◽  
Samuel I Rapaport
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Extrinsic Pathway ◽  
Step Model ◽  
Arginine Residues ◽  
Gla Domain ◽  
Positively Charged ◽  
Independent Reaction ◽  
Inhibit Factor

SummaryInhibition of factor VIIa/tissue factor (TF) by extrinsic pathway inhibitor (EPI) requires the participation of factor Xa. Through this inhibition, factor Xa generated initially may feed back to suppress continuing generation of factor Xa via the extrinsic pathway during hemostasis. We have utilized chemical modifications of EPI and factor Xa to study the reactions responsible for inhibition. The data are consistent with a two-step model. First, EPI binds to factor Xa in a Ca2+ independent reaction in which the gla-domain of factor Xa does not participate. A functional active site on factor Xa and arginine residues on EPI are essential for this step. Then the factor Xa/EPI complex binds to factor VIIa/TF with resultant inhibition of its enzymatic activity. The gla-domain of factor Xa is essential for this step. Intact positively charged lysines on factor Xa may also be important

scholarly journals The Non-Vitamin K Antagonist Oral Anticoagulants in Heart Disease: Section V—Special Situations

2018 ◽  
Vol 119 (01) ◽  
pp. 014-038 ◽  
Author(s):  
Raffaele De Caterina ◽  
Walter Ageno ◽  
Giancarlo Agnelli ◽  
Noel Chan ◽  
Hans-Christoph Diener ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Risk Profile ◽  
Vitamin K Antagonist ◽  
The Individual ◽  
The Right ◽  
Routine Coagulation ◽  
Inhibit Factor

AbstractNon-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit–risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug–drug interactions and preference for once- or twice-daily dosing. In addition, several ‘special situations’ were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.

SYNTHETIC PEPTIDE ANALOGS OF TISSUE FACTOR AND FACTOR VII WHICH INHIBIT FACTOR Xa FORMATION BY THE TISSUE FACTOR/FACTOR VIIa COMPLEX

1996 ◽  
Vol 84 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Helle F. Rønning ◽  
Unni C. Risøen ◽  
Lars Örning ◽  
Knut Sletten ◽  
Kjell S. Sakariassen
Keyword(s):  
Tissue Factor ◽  
Synthetic Peptide ◽  
Factor Viia ◽  
Factor Xa ◽  
Factor Vii ◽  
Peptide Analogs ◽  
Inhibit Factor

The salivary transcriptome of Limnobdella mexicana (Annelida: Clitellata: Praobdellidae) and orthology determination of major leech anticoagulants

Parasitology ◽  
2019 ◽  
Vol 146 (10) ◽  
pp. 1338-1346
Author(s):  
Rafael Iwama ◽  
Alejandro Oceguera-Figueroa ◽  
Gonzalo Giribet ◽  
Sebastian Kvist
Keyword(s):  
Amino Acid ◽  
Positive Relationship ◽  
Phylogenetic Analyses ◽  
Factor Xa ◽  
Amino Acid Conservation ◽  
Inhibit Factor

AbstractBloodfeeding requires several adaptations that allow the parasite to feed efficiently. Leeches and other hematophagous animals have developed different mechanisms to inhibit hemostasis, one of the main barriers imposed by their hosts. Limnobdella mexicana is a member of the leech family Praobdellidae, a family of host generalists known for their preference to attach on mucosal membranes of mammals, such as those in nasopharyngeal cavities, bladders and ocular orbits. Previous studies have hypothesized a positive relationship between diversity of anticoagulants and diversity of hosts in bloodfeeding leeches. However, orthology determination of putative anticoagulants and the lack of standardization of sequencing effort and method hinder comparisons between publicly available transcriptomes generated in different laboratories. In the present study, we examine the first transcriptome of a praobdellid leech and identify 15 putative anticoagulants using a phylogeny-based inference approach, amino-acid conservation, Pfam domains and BLAST searches. Our phylogenetic analyses suggest that the ancestral leech was able to inhibit factor Xa and that some hirudins that have been reported in previous studies on leech anticoagulants may not be orthologous with the archetypal hirudin.

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