Ignite Creation Date:
2024-05-06 @ 8:11 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06285435
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-29
First Post:
2024-02-22
Brief Title:
Coagulation Activation in Patients With Pemphigus
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Activation of Coagulation as an Indicator of a Pro-thrombotic State in Patients With Pemphigus A Case-control Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Aim of work
1 To evaluate the plasma markers of coagulation activation prothrombin F12 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
1 To evaluate the plasma markers of coagulation activation prothrombin F12 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
Detailed Description:
Pemphigus encompasses a group of autoimmune bullous diseases characterized clinically by the presence of flaccid blisters and erosions of the mucous membranes andor 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 07 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
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 07 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None