Level of protein C determined by combined assays during disseminated intravascular coagulation and oral anticoagulation

Abstract We have developed a variation of the solid-phase enzyme-linked immunosorbent assay (ELISA) to enable measurement of the activity and antigen levels of protein C (PC) in human plasma. With this assay it is possible to do both tests with the same sample and same microtiter plate coated with anti-PC monoclonal antibody (MCA)JTC-4, which inhibited neither activation of PC nor activity of activated PC (APC). Even in patients undergoing heparin treatment for severe disseminated intravascular coagulation, there were no detectable differences between amidolytic activity and antigen levels of PC in patients' plasma. In addition, there was a strong correlation between the immunologic levels of PC in patients' plasma determined both by polyclonal ELISA using peroxidase-labeled immunopurified antiprotein C-IgG and those found with MCA ELISA using peroxidase-labeled MCAJTC-5, which does not bind to APC. In contrast, when oral anticoagulation therapy was started, immunologic levels of plasma PC estimated by peroxidase-labeled MCAJTC- 1, a MCA that recognizes a gamma-carboxyglutamic acid domain-related conformational change of PC induced by metal ions, decreased more rapidly than did either the PC level determined by polyclonal ELISA or the percent prothrombin time. This suggested that comparison of MCAJTC- 1-recognized PC levels and prothrombin time may be necessary at the beginning of oral anticoagulation therapy to treat patients safely.

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Level of protein C determined by combined assays during disseminated intravascular coagulation and oral anticoagulation

Blood ◽

10.1182/blood.v69.6.1704.bloodjournal6961704 ◽

1987 ◽

Vol 69 (6) ◽

pp. 1704-1711

Author(s):

J Mimuro ◽

Y Sakata ◽

K Wakabayashi ◽

M Matsuda

Keyword(s):

Prothrombin Time ◽

Disseminated Intravascular Coagulation ◽

Oral Anticoagulation ◽

Protein C ◽

Solid Phase ◽

Anticoagulation Therapy ◽

Microtiter Plate ◽

Enzyme Linked Immunosorbent Assay ◽

Oral Anticoagulation Therapy ◽

Intravascular Coagulation

We have developed a variation of the solid-phase enzyme-linked immunosorbent assay (ELISA) to enable measurement of the activity and antigen levels of protein C (PC) in human plasma. With this assay it is possible to do both tests with the same sample and same microtiter plate coated with anti-PC monoclonal antibody (MCA)JTC-4, which inhibited neither activation of PC nor activity of activated PC (APC). Even in patients undergoing heparin treatment for severe disseminated intravascular coagulation, there were no detectable differences between amidolytic activity and antigen levels of PC in patients' plasma. In addition, there was a strong correlation between the immunologic levels of PC in patients' plasma determined both by polyclonal ELISA using peroxidase-labeled immunopurified antiprotein C-IgG and those found with MCA ELISA using peroxidase-labeled MCAJTC-5, which does not bind to APC. In contrast, when oral anticoagulation therapy was started, immunologic levels of plasma PC estimated by peroxidase-labeled MCAJTC- 1, a MCA that recognizes a gamma-carboxyglutamic acid domain-related conformational change of PC induced by metal ions, decreased more rapidly than did either the PC level determined by polyclonal ELISA or the percent prothrombin time. This suggested that comparison of MCAJTC- 1-recognized PC levels and prothrombin time may be necessary at the beginning of oral anticoagulation therapy to treat patients safely.

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Poor Agreement among Prothrombin Time International Normalized Ratio Methods: Comparison of Seven Commercial Reagents

Clinical Chemistry ◽

10.1373/clinchem.2004.043836 ◽

2005 ◽

Vol 51 (3) ◽

pp. 553-560 ◽

Cited By ~ 46

Author(s):

Juha Horsti ◽

Helena Uppa ◽

Juhani A Vilpo

Keyword(s):

Clinical Practice ◽

Patient Care ◽

Prothrombin Time ◽

Oral Anticoagulation ◽

Anticoagulation Therapy ◽

International Normalized Ratio ◽

Poor Agreement ◽

Oral Anticoagulation Therapy ◽

The Mean ◽

The Difference

Abstract Background: Prothrombin time (PT) has long been the most popular test for monitoring oral anticoagulation therapy. The International Normalized Ratio (INR) was introduced to overcome the problem of marked variation in PT results among laboratories and the various recommendations for patient care. According to this principle, all reagents should be calibrated to give identical results and the same patient care globally. This is necessary for monitoring of single patients and for application of the results of anticoagulation trials and guidelines to clinical practice. Methods: We took blood samples from 150 patients for whom oral anticoagulation had been prescribed. Plasmas were separated and PTs determined by use of seven commercial reagents and four calibrator sets. The differences in results were assessed by plotting, for each possible pair of methods, the differences in INR values for each sample against the mean INR value (Bland-Altman difference plots). Results: Mean results differed significantly (P <0.001) for 17 of 21 possible paired comparisons of methods. Only two pairs of methods produced very similar results when assessed for problems of substantial differences in INR values; a significant, systematic increase in the difference with INR; and a significant systematic increase in the variation in difference with increasing INR values. Conclusions: The agreement among several (and perhaps most) commercial INR methods is poor. The failure of current calibration strategies may severely compromise both the monitoring of individual patients and the application of oral anticoagulation guidelines and trial results to clinical practice.

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Protein C Levels in Disseminated Intravascular Coagulation and Thrombotic Thrombocytopenic Purpura: Its Correlation with Other Coagulation Parameters

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657869 ◽

1985 ◽

Vol 54 (02) ◽

pp. 445-449 ◽

Cited By ~ 29

Author(s):

Hoyu Takahashi ◽

Etsuko Takakuwa ◽

Noriko Yoshino ◽

Masaharu Hanano ◽

Akira Shibata

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Disseminated Intravascular Coagulation ◽

Protein C ◽

Geometric Mean ◽

Normal Subjects ◽

Mean Value ◽

Enzyme Linked Immunosorbent Assay ◽

Thrombocytopenic Purpura ◽

Intravascular Coagulation ◽

Synthetic Function

SummaryProtein C was measured by means of enzyme-linked immunosorbent assay (ELISA) in plasmas from 58 normal subjects, 39 patients with disseminated intravascular coagulation (DIC) and 5 patients with thrombotic thrombocytopenic purpura (TTP). Protein C levels ranged from 69.7 to 163.6% (95% confidence limits) in normal subjects. In patients with DIC, protein C concentrations were significantly decreased, with a geometric mean value of 42.1%. Protein C concentration was positively correlated with plasma prothrombin, antithrombin III and serum pseudocholinesterase, and was negatively correlated with von Willebrand factor antigen (vWF: Ag) and vWF: Ag/factor VIII ratio. These findings suggest that low protein C concentrations in DIC mean a consumption of protein C probably due to its activation by thrombin and/or impaired liver synthetic function. In patients with TTP, protein C levels were normal with a geometric mean value of 116.7%, indicating that the pathophysiology of TTP is quite different from that of DIC.

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Ervaringen tijdens de "Belgian Improvement Study on Oral Anticoagulation Therapy" (BISOAT)

Tijdschrift voor Geneeskunde ◽

10.2143/tvg.61.11.5002197 ◽

2005 ◽

Vol 61 (11) ◽

pp. 841-847 ◽

Cited By ~ 1

Author(s):

CLAES N ◽

BUNTINX F ◽

VIJGEN J ◽

ARNOUT J ◽

VERMYLEN J ◽

...

Keyword(s):

Oral Anticoagulation ◽

Anticoagulation Therapy ◽

Oral Anticoagulation Therapy

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Depression and Uptake of Oral Anticoagulation Therapy in Patients With Atrial Fibrillation

Medical Care ◽

10.1097/mlr.0000000000001268 ◽

2020 ◽

Vol 58 (3) ◽

pp. 216-224 ◽

Cited By ~ 1

Author(s):

Morten Fenger-Grøn ◽

Claus H. Vestergaard ◽

Lars Frost ◽

Dimitry S. Davydow ◽

Erik T. Parner ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulation ◽

Anticoagulation Therapy ◽

Oral Anticoagulation Therapy

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Oral Anticoagulation Therapy for Venous Thromboembolism in Norway: Time Trends and Treatment Patterns

Clinical Therapeutics ◽

10.1016/j.clinthera.2021.04.017 ◽

2021 ◽

Author(s):

Waleed Ghanima ◽

Anna Schultze ◽

Robert Donaldson ◽

Ellen Brodin ◽

Sigrun Halvorsen ◽

...

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulation ◽

Time Trends ◽

Anticoagulation Therapy ◽

Treatment Patterns ◽

Oral Anticoagulation Therapy

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Consideration of non-valvular atrial fibrillation with left atrial appendage thrombus formation despite under appropriate oral anticoagulation therapy

European Heart Journal ◽

10.1093/ehjci/ehaa946.0071 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H Shiraki ◽

H Tanaka ◽

K Yamashita ◽

Y Tanaka ◽

K Sumimoto ◽

...

Keyword(s):

Atrial Fibrillation ◽

Logistic Regression ◽

Regression Analysis ◽

Oral Anticoagulation ◽

Left Atrial ◽

Thrombus Formation ◽

Anticoagulation Therapy ◽

Left Ventricular ◽

Volume Index ◽

Oral Anticoagulation Therapy

Abstract Background Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population. In accordance with CHADS2 or CHA2DS2-VASc score, appropriate oral anticoagulation therapy such as warfarin or direct oral anticoagulants (DOAC) significantly reduced the risk of thromboembolic events. However, left atrial (LA) thrombus can be detected in the LA appendage (LAA) in AF patients despite appropriate oral anticoagulation therapy. Purpose Our purpose was to investigate the associated factors of LAA thrombus formation in non-valvular atrial fibrillation (NVAF) patients despite under appropriate oral anticoagulation therapy. Methods We retrospectively studied consecutive 286 NVAF patients for scheduled catheter ablation or electrical cardioversion for AF in our institution between February 2017 and September 2019. Mean age was 67.1±9.4 years, 79 patients (29.5%) were female, and 140 (52.2%) were paroxysmal AF. All patients underwent transthoracic and transesophageal echocardiography before catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy including warfarin or DOAC for at least 3 weeks prior to transesophageal echocardiography based on the current guidelines. LAA thrombus was defined as an echodense intracavitary mass distinct from the underlying endocardium and not caused by pectinate muscles by at least three senior echocardiologists. Results Of 286 NVAF patients with under appropriate oral anticoagulation therapy, LAA thrombus was observed in 9 patients (3.3%). Univariate logistic regression analysis showed that age, paroxysmal AF, CHADS2 score ≥3, left ventricular end-diastolic volume index (LVEDVI), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), LA volume index (LAVI), mitral inflow E and mitral e' annular velocities ratio (E/e'), and LAA flow were associated with LAA thrombus formation. It was noteworthy that multivariate logistic regression analysis showed that LAA flow was independent predictor of LAA thrombus (OR: 0.72, 95% CI: 0.59–0.89, p<0.005) as well as LVEF. Furthermore, receiver operating characteristic (ROC) curve analysis identified the optimal cutoff value of LAA flow for predicting LAA thrombus as ≤15cm/s, with a sensitivity of 88%, specificity of 93%, and area under the curve (AUC) of 0.95. Conclusions LAA flow was strongly associated with LAA thrombus formation even in NVAF patients with appropriate oral anticoagulation therapy. According to our findings, further strengthen of oral anticoagulation therapy or percutaneous transcatheter closure of the LAA may be considered in NVAF patients with appropriate oral anticoagulation therapy but low LAA flow, especially <15cm/s. Funding Acknowledgement Type of funding source: None

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Management of Oral Anticoagulation Therapy After Gastrointestinal Bleeding: Whether to, When to, and How to Restart an Anticoagulation Therapy

Annals of Pharmacotherapy ◽

10.1177/1060028017717019 ◽

2017 ◽

Vol 51 (11) ◽

pp. 1000-1007 ◽

Cited By ~ 9

Author(s):

Kazuhiko Kido ◽

Michael J. Scalese

Keyword(s):

Gastrointestinal Bleeding ◽

Cohort Studies ◽

Oral Anticoagulation ◽

Retrospective Cohort ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Cochrane Library ◽

Oral Anticoagulation Therapy ◽

Retrospective Cohort Studies

Objective: To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy. Data Sources: Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban.Study Selection and Data Extraction: All English-language studies assessing management of oral anticoagulation therapy after GIB were evaluated. Data Synthesis: A total of 9 studies were identified. Four retrospective cohort studies showed that resuming anticoagulation therapy was associated with significantly lower rate of thromboembolism (TE) in the general population. Meta-analyses and prospective cohort studies also supported this finding. Two retrospective cohort studies indicated an increase in GIB when anticoagulation reinitiation occurred in less than 7 days without a decrease in TE. Resuming therapy between 7 and 15 days did not demonstrate a significant increase in GIB or TE. A large retrospective study showed that apixaban was associated with the significantly lowest risk of GIB compared with both rivaroxaban and dabigatran. Conclusion: Anticoagulation therapy resumption is recommended, with resumption being considered between 7 and 14 days following GIB regardless of the therapy chosen. Data for warfarin management after GIB should be applied with caution to direct oral anticoagulants (DOACs) because of the quicker onset and experimental nature of reversal agents. Apixaban may be a preferred option when restarting a DOAC therapy.

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