Coagulation Activation in Patients With Pemphigus

February 22, 2024 updated by: Youstina Zaghloul, Assiut University

Activation of Coagulation as an Indicator of a Pro-thrombotic State in Patients With Pemphigus: A Case-control Study

Aim of work:

  1. To evaluate the plasma markers of coagulation activation: prothrombin F1+2 and d-dimer levels in pemphigus patients with active disease and compare them with age and sex-matched controls.
  2. To evaluate the correlation of these markers with disease severity score by using Pemphigus Disease Area Index (PDAI) and with disease activity by measurement of anti-desmoglein 1 and 3 antibody titers.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Pemphigus encompasses a group of autoimmune bullous diseases characterized clinically by the presence of flaccid blisters and erosions of the mucous membranes and/or skin. It is characterized by autoantibodies directed against the desmosomal desmogleins; Desmoglein 1 (Dsg1) and Desmoglein 3 (Dsg3) on keratinocyte cell surfaces resulting in acantholysis, which is the mechanism underlying pemphigus.

Pemphigus diseases can be classified into 4 main forms based on clinical and immunopathological features: pemphigus vulgaris, in about 70-80% of patients; pemphigus foliaceus, in about 20%; paraneoplastic pemphigus, in about 5%; and IgA pemphigus, in 1-3%.

The global incidence of PV ranges from 0.7 to 5 cases per million per year. PV predominantly affects adults in the 4th-6th decade of life. PV often begins with painful, non-healing erosions in oral mucosa, and develops into blisters in the skin.

The diagnosis of pemphigus is based on triad of history taking, clinical examination and immunologic investigations. ELISA using recombinant Dsgs enables detection of circulating autoantibodies in pemphigus. The sensitivity and specificity of anti-Dsg ELISA are 96% to 100% .The autoantibody titers often fluctuate in parallel with disease activity and decline with clinical improvement; therefore, these titers are useful not only for diagnosis but also for monitoring of disease activity and a decrease in the ELISA index value can be a useful guide for steroid tapering in the lesion-free phase.

Growing evidence has suggested that several autoimmune disorders are significantly associated with an increased risk of venous thromboembolism (VTE). However, the primary contribution of pemphigus to VTE development is unclear.

A retrospective cohort study demonstrated a 5% venous thromboembolism rate in patients with pemphigus within the first year after diagnosis.

A large-scale population-based longitudinal cohort study concluded that pemphigus is associated with an increased risk of pulmonary embolism (PE), particularly during the 1st year of the disease.

The mechanism underlying the increased VTE risk in pemphigus had not been clearly defined. However, there is evidence that systemic inflammation, which exists in pemphigus as well as in other autoimmune diseases, may promote thrombosis through upregulation of pro-coagulation systems, anticoagulant suppression, and antifibrinolytic effects. Elevated levels of tumor necrosis alpha (TNF-α) and interleukin (IL)-1, IL-6 and IL-8 released into systemic circulation have been found to promote coagulation.

Additional possible risk factors for VTE development in patients with pemphigus are hospitalization, immobility and high prevalence of infections. Corticosteroid therapy, the mainstay of pemphigus treatment, increases the risk of VTE by increasing the levels of fibrinogen and clotting factors.

D-Dimer is a biomarker of fibrin formation and degradation. So far, the guidelines for the diagnosis and treatment of PE have clearly stated that only D-dimer tests are used in laboratory tests for diagnosis to date.

Although D-dimer is considered a sensitive biomarker for thromboembolic events, it does not show as much specificity. Other conditions can also raise D-dimer level, such as pregnancy, renal failure and sepsis. An elevated D-dimer value is not sufficient to establish the diagnosis of pulmonary thromboembolism.

The most important marker of coagulation activation is the prothrombin fragment 1 + 2 (F1 + 2), which is a small peptide released when prothrombin is converted to thrombin by the prothrombinase complex on negatively charged phospholipids expressed on membranes of activated platelets. Consequently, an increased rate of conversion of prothrombin to thrombin, as it may occur in prothrombotic states, should result in an increase of F1 + 2 concentration in plasma. Owing to its relatively short half-life (approximately 90 minutes), the plasma levels of F1 + 2 are considered as reliable estimates of thrombin formation in vivo at the time of blood sampling.

Study Type

Observational

Enrollment (Estimated)

54

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients with active pemphigus who are either in a relapse for less than a week or are newly diagnosed cases will be included. The active stage of PV is defined as the de novo development of blisters on a healthy (unaffected or healed) site of either the skin or the mucous membrane.

Clinical assessment, histopathological analysis (acantholysis and intraepidermal splitting) will be used to confirm the diagnosis of each patient.

Control group: Healthy age and sex-matched subjects, who are free of chronic systemic diseases or dermatological conditions, will be enrolled as control.

Description

Inclusion Criteria:

  • pemphigus vulgaris patients at active stage of the disease.
  • patients between the ages of 18 and 60.

Exclusion Criteria:

  • Patients with other autoimmune bullous diseases.
  • Patients with other skin diseases.
  • Patients with chronic liver, renal or haematological diseases.
  • Patients with malignant tumors.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
control group
Diagnostic test: prothrombin fragment 1+2
Blood sample
Other Names:
  • D-dimer
pemphigus vulgaris patients
Diagnostic test: prothrombin fragment 1+2
Blood sample
Other Names:
  • D-dimer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of coagulation activation markers in pemphigus patients with controls
Time Frame: Baseline
Evaluate the plasma markers of coagulation activation: prothrombin F1+2 and d-dimer levels in pemphigus patients with active disease and compare them with age and sex-matched controls.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of markers with disease severity
Time Frame: Baseline
Evaluate correlation of these markers with disease severity score by using Pemphigus Disease Area Index (PDAI) and with disease activity by measurement of anti-desmoglein 1 and 3 antibody titers.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

February 22, 2024

First Submitted That Met QC Criteria

February 22, 2024

First Posted (Estimated)

February 29, 2024

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • coagulation activation in PV

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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