|Year : 2022 | Volume
| Issue : 3 | Page : 247-251
|Hemostatic and coagulation profile in psoriasis: A hospital-based case control Study
Mubashar M Mir1, Devraj Dogra1, Kuldeep K Koul2
1 Post Graduate Departments of Dermatology, Government Medical College, Jammu, Jammu and Kashmir, India
2 Department of Pathology, Government Medical College, Jammu, Jammu and Kashmir, India
|Date of Web Publication||22-Sep-2022|
Mubashar M Mir
H. No 131, Mohalla Gujjarabad, Roopnagar Bypass Road, Jammu, Jammu and Kashmir - 180 013
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Psoriasis is a chronic inflammatory dermatosis associated with an increased risk of cardiovascular disease and atherothrombosis. Aims: This study was conducted to assess the levels of various hemostatic and coagulation parameters in psoriasis and their correlation with disease severity. Settings and Design: This was a hospital-based observational study. Methods and Material: Seventy-five patients with psoriasis and seventy controls were included in the study. History taking, clinical examination, and calculation of Psoriasis Area and Severity Index (PASI) were done. Blood analysis for Platelet count (PC), mean platelet volume (MPV), Vitamin B12, Thrombin Time (TT), Prothrombin time (PT) and Activated partial thromboplastin time (APPT) were done in both groups. Results: MPV which is a marker of inflammation and platelet activation was significantly increased in cases and positively correlated with the disease severity. Vitamin B12 is an important cofactor in homocysteine (Hcy) metabolism and correlates inversely with serum Hcy which is a known atherothrombotic marker. Vitamin B12 levels were significantly decreased in the cases with a significant negative correlation between Vitamin B12 level and PASI. There was also a significant decrease in serum level of PT, aPTT and TT in cases as compared to controls; however they showed no significant correlation with PASI. Conclusions: Inflammation in psoriasis may drive the process of abnormal platelet activation and coagulation abnormalities thus predisposing psoriatic patients to an atherothrombotic state and increasing the cardiovascular risk in psoriatic patients.
Keywords: Atherothrombosis, coagulation, hemostatic markers, psoriasis
|How to cite this article:|
Mir MM, Dogra D, Koul KK. Hemostatic and coagulation profile in psoriasis: A hospital-based case control Study. Indian J Dermatol 2022;67:247-51
|How to cite this URL:|
Mir MM, Dogra D, Koul KK. Hemostatic and coagulation profile in psoriasis: A hospital-based case control Study. Indian J Dermatol [serial online] 2022 [cited 2022 Sep 30];67:247-51. Available from: https://www.e-ijd.org/text.asp?2022/67/3/247/356746
| Introduction|| |
It is now believed that psoriasis is not just a cutaneous disease but a systemic inflammatory disease characterized by increased inflammatory biomarkers in the blood which may contribute to cardiovascular morbidity in psoriasis. Patients with psoriasis have almost twice the risk of cardiovascular disease when compared with normal controls. Also, arteriovenous vascular occlusion is more common among psoriatic than non-psoriatic dermatological patients. Along with endothelial dysfunction, psoriasis patients also have an increase in circulating endothelial cells and microparticles, which may promote coronary artery disease, acute coronary syndromes, and atherothrombosis.
Platelet Distribution Width (PDW) and mean platelet volume (MPV) have been extensively studied and reported as platelet activation markers, their levels are shown to be raised in various diseases such as cardiovascular disease, peripheral artery disease, systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, osteoarthritis, vascular dementia, and Alzheimer's disease.,,, Moreover, MPV correlates with platelet activity and is considered a marker of platelet activation and inflammation. Younger platelets produced, due to marked activation of megakaryocytes by cytokines, are larger in size. These large thrombocytes show a greater content of cell granules, display higher expression of adhesion molecules, and an increased activity. Although MPV levels have been studied in many diseases, and there is limited data about it in patients with psoriasis.
Vitamin B12 is an important cofactor in homocysteine metabolism. It was found that higher homocysteine levels were associated with lower vitamin B12 levels in psoriasis patients. Thus, vitamin B12 levels were studied as an indirect hemostatic marker in place of homocysteine since it is more easily available blood test in resource-poor setup like ours.
While some studies suggest that inflammation plays a central role in the pathogenesis of atherosclerosis and atherothrombosis, the potential association between inflammation and risk of thromboembolism in psoriasis is, however, unclear at present.
The present study was undertaken to further elucidate in detail the hemostatic variables and coagulation profile in psoriasis patients and to compare them with controls besides their correlation with disease severity.
| Subjects and Methods|| |
The study was conducted in a tertiary care hospital in North India for 1 year in 2019 after obtaining approval from the institutional ethics committee. It was a hospital-based case-control study in which patients reporting to the Department of Dermatology were evaluated for entry into the study. Written informed consent was taken from the patients and controls. The sample size was calculated using Epi Info program for windows version 10 using a confidence interval of 99% and power of the study as 90%. Values of exposure for cases and controls were adopted from a study by Vanizor Kural et al.
In this study, a case was defined as a patient clinically diagnosed with cutaneous psoriasis by a dermatologist. Control group comprised of age- and sex-matched patients attending dermatology OPD for diseases not known to affect coagulation or inflammatory pathways and attendants of patients attending the department.
Inclusion criteria included clinically diagnosed patients of cutaneous psoriasis and patients willing to participate in the study. Exclusion criteria included cases of psoriatic arthritis without cutaneous involvement, diagnosis of other diseases that could alter the coagulation cascade, use of anticoagulant therapy at the time of study, patients with obesity (body mass index >30 kg/m2), diabetes mellitus, dyslipidemia, hypertension or severe cardiovascular disease, any history of previous venous thromboembolic disease, chronic hepatic or renal diseases, autoimmune disorders, neoplasms or recent trauma, patients on medications known to cause significant hyperhomocysteinemia such as phenytoin, carbamazepine, theophylline, azathioprine, metformin, and thiazide diuretics. Patients who refused to give consent to undergo investigations, pregnant and lactating patients were also excluded from the study.
Both patients and controls were subjected to detailed history and examination regarding age of onset, type, and distribution of lesions, progression, duration, family history, personal histories like smoking and alcohol intake. Relevant information was taken and recorded on a predesigned proforma. Grading of the severity of the disease was done based on PASI Score. PASI Score <10 was graded as mild whereas PASI Score >10 was graded as moderate to severe.,
Basic investigations like complete blood counts, liver and kidney function, and ECG were done in all. Special laboratory investigations included prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), MPV, platelet count (PC), and serum Vitamin B12. Normal range values were as follows: PT (11.0–12.5 s), aPTT (30–40 s), TT (15–19 s), MPV (7.2 and 11.7 fl), PC (1.5–4 lakh).
Morning blood samples of both cases and controls were obtained from the antecubital brachial vein without a tourniquet after 8 hours of fasting with a venipuncture needle. ASPEN Mindray BC-5800 auto hematology analyzer (Mindray Bio-Medical Electronics Co. Ltd., Shenzhen, China) was utilized for complete blood count including platelet count and MPV. Vitamin B12 levels were determined by the immune-enzyme assay method using the ARCHITECT i1000SR immunoassay analyzer (Abbott Laboratories, Abbott Park, Illinois, U.S.A). Coagulation studies i.e. Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT) and Thrombin Time (TT) were done with citrated blood samples using ACL Elite Coagulation Analyzer (Beckman Instrumentation Laboratory, U.S.A). Original reagents and kits were used in all cases.
Data were collected and analyzed using Microsoft Excel and SPSS 22.0. Categorical data were represented as numbers and percentages while continuous data were expressed as mean and standard deviation. Comparison of blood parameters between groups was done using Mann Whitney's test. Correlational analysis was done using the Spearman's correlation coefficient (r). A value of P < 0.01 was taken as statistically significant.
| Results|| |
The study consisted of 75 cases and 70 controls. This psoriatic group had slight male domination (42, 56%) and a mean age of 29.5 years (standard deviation ± 8.2) whereas the control group included 38 males (54%) and a mean age of 31.23 years (standard deviation ± 7.8). The demographics and baseline clinical parameters were tabulated for both groups [Table 1]. The cases and controls were matched for age and sex. Comparison of blood parameters between the study and control group was done. MPV levels were found to be higher among cases (12.9 ± 2.1 fl.) as compared to controls (7.3 ± 3.41 fl.). Also, Vitamin B12 was lower (144.1 ± 85.2 pg/ml) as compared to controls (331.5 ± 67.6 pg/ml). The difference between both groups was found to be statistically significant for both MPV and Vitamin B12 (P < 0.01). As far as the coagulation parameters were concerned, patients of psoriasis had lower levels of PT (8.5±1.8 secs. vs 11.4±1.3 secs.), TT (16.2±1.8 vs 19.1±1.3)and aPTT (26.2±1.8 vs 29.2±2.3) as compared to controls. The difference between both groups was found to be statistically significant (P < 0.01). Platelet count was however comparable between cases and controls (P > 0.01) [Table 2]. With respect to personal habits, only PT was decreased among both cases and controls in smokers as compared to nonsmokers; however, the difference was not statistically significant.
|Table 1: Demographics and baseline characteristics of the study and control groups|
Click here to view
So far as disease severity was concerned, correlation of blood parameters was done with PASI score. MPV showed a moderately positive correlation with PASI score (r = 0.547, P < 0.01), while the levels of Vitamin B12 (r = -0.402, P < 0.01) showed a moderately negative correlation with PASI. The correlation of PT, aPTT, TT and platelet count was not statistically significant [Table 3].
With respect to the duration of disease, only MPV showed a moderately positive increase (r = 0.422, P < 0.01) [Table 4].
| Discussion|| |
In this study, the patients with psoriasis had significantly decreased PT, TT and aPTT as compared to controls. This was in partial concordance with a study by Ahmed et al. which revealed a hypercoagulable state supported by a significant decrease in PT levels of the studied psoriasis patients when compared with control group; however aPTT in this study by Ahmed et al did not show a significant difference between the cases and controls. Our findings with regards to coagulation factors i.e. PT and aPTT were in disagreement with a study by Karbudak et al. who found no significant difference between PT and aPTT of psoriasis patients and control group.
In this study, the patients with psoriasis also had significantly lower levels of vitamin B12 as compared to controls. The results were similar to a study by Vanizor Kural et al. who studied 30 psoriatic patients and 30 controls and found lower vitamin B12 levels among psoriatic patients as compared to the controls. In another study, a significant negative correlation was observed between the levels of serum Homocysteine and serum Vitamin B12 in the studied psoriasis patients. This may be linked to the fact that Vitamin B12 is an important cofactor in Homocysteine metabolism and its deficiency can lead to hyper-homocysteinemia. Homocysteine is considered an established risk factor for atherosclerosis and thrombosis, because it may cause direct endothelial injury by oxidative damage to the endothelium followed by facilitated thrombosis. Thus, Vitamin B12 deficiency indirectly may play an important role for the development of atherothrombotic events in patients with psoriasis.
MPV has been used as a biochemical marker studied in various inflammatory disorders; however, it has not been studied much in patients with psoriasis before. In our study MPV levels were found to be higher among cases as compared to controls. The difference was found to be statistically significant. Similar results were obtained in a study by Canpolat et al. who studied the MPV levels in the psoriatic arthritis group (9.5 ± 0.8 fl); psoriasis group (8.0 ± 0.7 fl) and the control group (7.3 ± 0.8 fl) (P < 0.01) suggesting that the MPV was higher in both psoriasis and psoriatic arthritis groups compared with the control. Increase in MPV may also be contributed by the consumption of platelets in the process of thrombosis followed by release of younger platelets from the bone marrow to the peripheral blood circulation which are larger in size than the mature platelet cells. Our findings reinforce the hypothesis that endothelial inflammation can trigger endothelial dysfunction, platelet activation and hypercoagulation in psoriasis.
In the present study, based on the correlation of blood parameters with severity of the disease (PASI score), the levels Vitamin B12 showed a negative correlation with PASI Score. Correlation of PT, aPTT, TT and Platelet count was however not statistically significant. The results of this study were similar to a previous study where a significant negative correlation was observed between PASI score and PT, aPTT. However, homocysteine levels showed a positive correlation with PASI. Also in our study, MPV showed a significant positive correlation with PASI score. The results were contrary to a study by Cannapolat et al. which showed that MPV levels positively correlated with PASI score. Another study by Kılıç et al. showed a weak positive correlation between MPV and PASI and suggested that the elevated MPV level may be used as an informative parameter to evaluate psoriasis severity.
Based on the relation between blood parameters and duration of disease, in the present study, only the MPV levels were found to be higher in patients with longer disease durations. The correlation of increase in the MPV with disease duration was statistically significant (P < 0.01). This was similar to observations in a study by Canpolat et al. who found that MPV levels showed a positive correlation with disease duration. This study reiterates previous observations indicating increased platelet activation in psoriasis which may increase with an increase in disease duration.
It is thus concluded that psoriasis, being a systemic inflammatory disease has increased expression of circulating inflammatory cytokines which may promote endothelial inflammation and endothelial cell dysfunction. This in turn may trigger platelet activation and coagulation abnormalities in patients of psoriasis which increases the risk to develop atherothrombosis and increase likelihood of its manifestations like cardiovascular events. Increased homocysteine and decreased vitamin B12 levels in psoriasis may itself contribute to this by causing direct oxidative damage to the endothelium.
Limitations of our study were the fact that our sample size was small. Other important blood parameters like serum homocysteine, cofactors in homocysteine metabolism like vitamin B6 and folic acid levels were not measured due to the non-availability of the facility. Also, Antithrombin 3 and platelet distribution width (PDW) levels were not done due to non-availability.
We recommend that psoriatic patients, especially those with higher disease severity, longer disease duration, and those with other predisposing factors to thrombosis, as well as those in need of a prolonged stay in hospital, should be carefully monitored in order to prevent venous thrombosis, cardiovascular disease and their complications. Further studies are required to explore in detail the role of hemostatic and coagulation parameters in psoriatic patients and their potential diagnostic and prognostic utility. The role of vitamin B12 supplementation and possible use of antiplatelet drugs in such patients warrants further studies before they can be put to clinical use in such scenarios.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Boehncke WH. Systemic inflammation and cardiovascular comorbidity in psoriasis patients: Causes and consequences. Front Immunol 2018;9:579.
Tobin A-M, Hughes R, Hand EB, Leong T, Graham IM, Kirby B. Homocysteine status and cardiovascular risk factors in patients with psoriasis: A case-control study. Clin Exp Dermatol 2011;36:19-23.
Schmidt DE, Manca M, Hoefer IE. Circulating endothelial cells in coronary artery disease and acute coronary syndrome. Trends Cardiovasc Med 2015;25:578-87.
Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: A link between thrombosis and inflammation. Curr Pharm Des 2011;17:47-58.
Pauling JD, O'Donnell VB, Mchugh NJ. The contribution of platelets to the pathogenesis of Raynaud's phenomenon and systemic sclerosis. Platelets 2013;24:503-15.
Balbaloglu O, Korkmaz M, Yolcu S, Karaaslan F, Beceren NGC. Evaluation of mean platelet volume (MPV) levels in patients with synovitis associated with knee osteoarthritis. Platelets 2014;25:81-5.
Liang Q-C, Jin D, Li Y, Wang R-T. Mean platelet volume and platelet distribution width in vascular dementia and Alzheimer's disease. Platelets 2014;25:433-8.
Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB. Mean platelet volume is a risk factor for venous thromboembolism: The tromso study. J Thromb Haemost 2010;8:157-62.
Işik S, Kılıç S, Öğretmen Z, Çakır DÜ, Türkön H, Cevizci S, et al
. The correlation between the psoriasis area severity index and ischemia-modified albumin, mean platelet volume levels in patients with psoriasis. Dermatol Allergol 2016;33:290-3.
Bowcock AM, Krueger JG. Getting under the skin: The immunogenetics of psoriasis. Nat Rev Immunol 2005;5:699-711.
Vanizor Kural B, Orem A, Cimşit G, Uydu HA, Yandi YE, Alver A. Plasma homocysteine and its relationship with atherothrombotic markers in psoriatic patients. Clin Chim Acta 2003;332:23-30.
Hansson GK. Inflammation, atherosclerosis and coronary artery disease. N Engl J Med 2005;352:1685-95.
Finlay AY, Kelly SE. Psoriasis: An index of disability. Clin Exp Dermatol 1987;12:8-11.
Pagana KD, Pagana TJ, Pagana TN. Mosby's Diagnostic and Laboratory Test Reference. 14th
ed. St. Louis, Mo: Elsevier; 2019.
Ahmed AWS, Jehan HS, Fatma ME, Osama HA. Markers of inflammation and thrombophilia in psoriasis. Med J Cairo Univ 2014;82:127-31.
Karabudak O, Ulusoy RE, Erikci AA, Solmazgul E, Dogan B, Harmanyeri Y. Inflammation and hypercoagulable state in adult psoriatic men. Acta Derm Venereol 2008;88:337-40.
Malebra M, Gisondi P, Radaeli A, Sala R, Calzavara Pinton PG, Girolomoni G. Plasma homocysteine and folate levels in patients with chronic plaque psoriasis. Br J Dermatol 2006;155:1165-9.
Varga EA, Sturm AC, Misita CP. Cardiology patient pages. Homocysteine and MTHFR mutation: Relation to thrombosis and coronary artery disease. Circulation 2005;111:e289-93.
Canpolat F, Akpinar H, Eskioglu F. Mean platelet volume in psoriasis and psoriatic arthritis. Clin Rheumatol 2010;29:325-8.
Kılıç S, Reşorlu H, Işik S, Oymak S, Akbal A, Hız MM, et al
. Association between mean platelet volume and disease severity in patients with psoriasis and psoriatic arthritis. Postepy Dermatol Alergol 2017;34:126-30.
[Table 1], [Table 2], [Table 3], [Table 4]
| Article Access Statistics|
| Viewed||148 |
| Printed||2 |
| Emailed||0 |
| PDF Downloaded||15 |
| Comments ||[Add] |