Systemic Anticoagulant Effect of Low-Dose Subcutaneous Unfractionated Heparin as Determined Using Thrombelastography

In an observational study using heparinase-modified thrombelastography, we investigated the percentage of elective cardiothoracic surgical patients receiving low-dose unfractionated heparin (5000 IU 12 hourly subcutaneously) who had a demonstrable systemic heparin effect. Blood samples were obtained at induction from 40 adult elective cardiothoracic surgical patients who had received 5000 IU unfractionated heparin subcutaneously within six hours. Simultaneous kaolin and heparinase-modified thrombelastographies were run on all samples. Fourteen patients (35%; 95% CI: 20 to 50%) had a demonstrable heparin effect(defined as a kaolin thrombelastography R time >25% longer than the heparinase-modified control). Their mean±SD kaolin thrombelastography R time was 13.6±5.9 minutes (normal range 4 to 8 minutes) vs. 7.1±2.0 minutes for the heparinase-modified controls. In 10 patients the thrombelastography R times were >50% longer and in four patients >100% longer, than their respective heparinase-modified controls. In a post hoc analysis, there was little correlation between the extent of the prolongation and patient age (r=0.02), weight (r=-0.31), preoperative creatinine (r=-0.17), or time since administration of heparin (r=0.14). These results indicate that about one third of patients who have received low-dose unfractionated heparin subcutaneously within six hours have a demonstrable heparin effect. The potential for this effect should be considered if central neural blockade is planned.

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Faculty Opinions recommendation of Discontinuation of continuous renal replacement therapy: a post hoc analysis of a prospective multicenter observational study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1164235.624934 ◽

2009 ◽

Author(s):

Michael Joannidis ◽

Julia Hasslacher

Keyword(s):

Renal Replacement Therapy ◽

Observational Study ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Multicenter Observational Study ◽

Post Hoc Analysis ◽

Post Hoc ◽

Prospective Multicenter Observational Study

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Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study

Arthritis Research & Therapy ◽

10.1186/s13075-021-02535-6 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Miao Miao ◽

Xian Xiao ◽

Jiayi Tian ◽

Yunzhi Zhufeng ◽

Ruiling Feng ◽

...

Keyword(s):

Low Dose ◽

Activity Index ◽

Cell Subset ◽

Immunoglobulin M ◽

Controlled Clinical Trial ◽

Double Blind ◽

Post Hoc Analysis ◽

Immune Balance ◽

Cell Balance ◽

Post Hoc

Abstract Objective To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial. Methods A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets. Results Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance. Conclusion These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance. Trial registration number ClinicalTrials.gov Registries (NCT02465580).

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