On ignoring instead of chasing after coagulation factor VII during warfarin management; an interrupted time series study

During warfarin management, prothrombin time (PT) based PT-INR variability is partly due to clinically inconsequential fluctuations of factor (F) VII. The new Fiix-PT and Fiix-normalized ratio (Fiix-NR), unlike PT-INR, is only affected by reduced FII and FX. Starting July 1st 2016 we replaced PT-INR monitoring of warfarin with Fiix-NR in our patients. Using interrupted time series methods, we retrospectively assessed if this affected thromboembolism (TE) and major bleeding (MB) incidence during 12 months prior to and 18 months after the replacement, months 13-18 being predefined as transitional months. The dynamic cohort comprised all our service´s 2,667 maintenance phase warfarin patients managed at any time during the 30 months. Using two-segmented regression, a breakpoint in total TE monthly incidence became evident six months after laboratory monitoring test replacement, followed by 56% reduction in TE incidence (from 2.82% to 1.23% per patient year, P=0.019 by ANOVA). Three-segmented regression found no significant TE incidence trend (slope +0.03) prior to test replacement but during months 13-18 and 19-30 the TE incidence gradually decreased (slope -0.12; R2=0.20;P=0.007). Based on segmented regressions, MB incidence (2.79% ppy) did not differ pre- or post-intervention. Incidence comparison during the 12 month Fiix- and PT-periods confirmed a statistically significant 55-62% reduction in TE. Fiix-monitoring reduced testing, dose adjustments and normalized ratio variability, and prolonged testing intervals and time in range. We conclude that ignoring FVII during Fiix-NR monitoring in real world practice stabilizes the anticoagulant effect of warfarin and associates with major reduction in thromboembolism without increasing bleeding.

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Reflection on modern methods: a common error in the segmented regression parameterization of interrupted time-series analyses

International Journal of Epidemiology ◽

10.1093/ije/dyaa148 ◽

2020 ◽

Author(s):

Hong Xiao ◽

Orvalho Augusto ◽

Bradley H Wagenaar

Keyword(s):

Time Series ◽

Randomized Study ◽

Interrupted Time Series ◽

Linear Segment ◽

Segmented Regression ◽

Calendar Time ◽

Post Intervention ◽

Common Error ◽

Indicator Variable ◽

Intervention Level

Abstract Interrupted time-series (ITS) designs are a robust and increasingly popular non-randomized study design for strong causal inference in the evaluation of public health interventions. One of the most common techniques for model parameterization in the analysis of ITS designs is segmented regression, which uses a series of indicators and linear terms to represent the level and trend of the time-series before and after an intervention. In this article, we highlight an important error often presented in tutorials and published peer-reviewed papers using segmented regression parameterization for the analyses of ITS designs. We show that researchers cannot simply use the product between their calendar time variable and the indicator variable indicating pre- versus post-intervention time periods to represent the post-intervention linear segment. If researchers use this often-presented parameterization, they will get an erroneous result for the level change in their time-series. We show that researchers must take care to use the product between their intervention variable and the time elapsed since the start of the intervention, rather than the time since the beginning of their study. Thus, the second linear segment of the time-series indexing the post-intervention level and trend should be zero before intervention implementation and begin by counting from zero, rather than counting from the time elapsed since the beginning of the study. We hope that this article can clarify segmented regression parameterization for the analysis of ITS designs and help researchers avoid confusing and erroneous results in the level changes of their time-series.

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LB-16. Association Between Universal Face Shield in a Quaternary Care Center and Reduction of SARS-COV2 Infections Among Healthcare Personnel and Hospitalized Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa515.1913 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S851-S851

Author(s):

Vagesh Hemmige ◽

Becky Winterer ◽

Todd Lasco ◽

Bradley Lembcke

Keyword(s):

Time Series ◽

Care Center ◽

Interrupted Time Series ◽

Hospitalized Patients ◽

Healthcare Personnel ◽

Segmented Regression ◽

Intervention Period ◽

Interrupted Time Series Analysis ◽

Post Intervention ◽

The Impact

Abstract Background SARS-COV2 transmission to healthcare personnel (HCP) and hospitalized patients is a significant challenge. Our hospital is a quaternary healthcare system with more than 500 beds and 8,000 HCP. Between April 1 and April 17, 2020, we instituted several infection prevention strategies to limit transmission of SARS-COV2 including universal masking of HCP and patients, surveillance testing every two weeks for high-risk HCP and every week for cluster units, and surveillance testing for all patients on admission and prior to invasive procedures. On July 6, 2020, we implemented universal face shield for all healthcare personnel upon entry to facility. The aim of this study is to assess the impact of face shield policy on SARS-COV2 infection among HCP and hospitalized patients. Figure 1- Interrupted time series Methods The preintervention period (April 17, 2020-July 5, 2020) included implementation of universal face masks and surveillance testing of HCP and patients. The intervention period (July 6, 2020-July 26, 2020) included the addition of face shield to all HCP (for patient encounters and staff-to-staff encounters). We used interrupted time series analysis with segmented regression to examine the effect of our intervention on the difference in proportion of HCP positive for SARS-COV2 (using logistic regression) and HAI (using Poisson regression). We defined significance as p values < 0.05. Results Of 4731 HCP tested, 192 tested positive for SARS-COV2 (4.1%). In the preintervention period, the weekly positivity rate among HCP increased from 0% to 12.9%. During the intervention period, the weekly positivity rate among HCP decreased to 2.3%, with segmented regression showing a change in predicted proportion positive in week 13 (18.0% to 3.7%, p< 0.001) and change in the post-intervention slope on the log odds scale (p< 0.001). A total of 14 HAI cases were identified. In the preintervention period, HAI cases increased from 0 to 5. During the intervention period, HAI cases decreased to 0. There was a change between pre-intervention and post-intervention slope on the log scale was significant (p< 0.01). Conclusion Our study showed that the universal use of face shield was associated with significant reduction in SARS-COV2 infection among HCP and hospitalized patients. Disclosures All Authors: No reported disclosures

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Coagulation Factor VII, Dietary Fat and Blood Lipids: A Review

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650609 ◽

1996 ◽

Vol 76 (04) ◽

pp. 492-499 ◽

Cited By ~ 50

Author(s):

L I Mennen ◽

E G Schouten ◽

D E Grobbee ◽

C Kluft

Keyword(s):

Dietary Fat ◽

Blood Lipids ◽

Coagulation Factor ◽

Factor Vii ◽

Coagulation Factor Vii

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A Polymorphic Cluster in the 5′ Region of the Human Coagulation Factor VII Gene: Detection, Frequency, and Linkage Disequilibrium

Thrombosis Research ◽

10.1016/s0049-3848(97)00273-9 ◽

1997 ◽

Vol 88 (5) ◽

pp. 445-448 ◽

Cited By ~ 15

Author(s):

Giorgio Dell'Acqua ◽

Licia Iacoviello ◽

Andria D'Orazio ◽

Rosa Di Bitondo ◽

Augusto Di Castelnuovo ◽

...

Keyword(s):

Linkage Disequilibrium ◽

Coagulation Factor ◽

Factor Vii ◽

Gene Detection ◽

Coagulation Factor Vii ◽

Detection Frequency ◽

Human Coagulation Factor Vii

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Novel factor VII gene mutations in six families with hereditary coagulation factor VII deficiency

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23905 ◽

2021 ◽

Author(s):

Xiaoyu Zhang ◽

Shuwen Wang ◽

Shaoqiu Leng ◽

Qi Feng ◽

Yanqi Zhang ◽

...

Keyword(s):

Gene Mutations ◽

Coagulation Factor ◽

Factor Vii ◽

Coagulation Factor Vii ◽

Factor Vii Deficiency

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The use of recombinant activated coagulation factor VII for spine surgery

Haemostasis in Spine Surgery ◽

10.1007/3-540-27394-8_14 ◽

2005 ◽

pp. 83-88

Author(s):

Richard B. Weiskopf

Keyword(s):

Spine Surgery ◽

Coagulation Factor ◽

Factor Vii ◽

Coagulation Factor Vii

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Coagulation Factor VII and Plasma Triglycerides

Pathophysiology of Haemostasis and Thrombosis ◽

10.1159/000215904 ◽

1989 ◽

Vol 19 (3) ◽

pp. 125-130 ◽

Cited By ~ 2

Author(s):

J. Carvalho de Sousa ◽

E. Bruckert ◽

P. Giral ◽

C. Soria ◽

J. Chapman ◽

...

Keyword(s):

Coagulation Factor ◽

Factor Vii ◽

Plasma Triglycerides ◽

Coagulation Factor Vii

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A case of an inhibitor autoantibody to coagulation factor VII

Haemophilia ◽

10.1046/j.1365-2516.2003.00714.x ◽

2003 ◽

Vol 9 (1) ◽

pp. 119-120 ◽

Cited By ~ 10

Author(s):

C. Aguilar ◽

J. F. Lucía ◽

P. Hernández

Keyword(s):

Coagulation Factor ◽

Factor Vii ◽

Coagulation Factor Vii

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Circulating Tissue Factor Procoagulant Activity and Thrombin Generation in Patients with Type 2 Diabetes: Effects of Insulin and Glucose

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0933 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4352-4358 ◽

Cited By ~ 83

Author(s):

Guenther Boden ◽

Vijender R. Vaidyula ◽

Carol Homko ◽

Peter Cheung ◽

A. Koneti Rao

Keyword(s):

Type 2 Diabetes ◽

Tissue Factor ◽

Blood Coagulation ◽

Coagulation Factor ◽

Procoagulant Activity ◽

Factor Vii ◽

Coagulation Factor Vii ◽

Glucose Levels ◽

Study Protocols

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

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