Patients with Alopecia Areata Have Higher Levels of Markers of Venous Thrombembolism

Authors Suggest More Evidence for Possible Risk of Blood Clots Among Patients with Alopecia Areata

In the past few years, I have reviewed with readers the many diseases that may be more likely to occur in patients with alopecia areata. These include heart disease, strokes, metabolic syndrome, thyroid disease and several others.

More recently, I have discussed the issue of blood clots in patients with alopecia areata.

A 2015 study sought to evaluate serum concentrations of selectins in patients with alopecia areata and examine whether they correlate with disease severity and activity. Selectins are a family (P‐selectin, E‐selectin, L‐selectin) of glycoproteins that facilitate and augment thrombosis as well as inflammation. P‐ and E‐selectin have been investigated as potential biomarkers for thrombosis. The study consisted of 64 patients with AA and 40 healthy control subjects. Results of the study showed a statistically significantly higher levels of E, P, L-selectins in AA patients compared with the healthy control group. Serum concentrations of soluble forms of E- and L-selectins correlated with the severity of the disease. E-selectin levels correlated with AA disease activity.

A 2021 study by Shakoei  S et al suggested that patients with alopecia areata had higher D dimer levels compared to controls. This raised the possibility of a deficiency in the coagulation pathway in patients with alopecia areata. An interesting 2021 study by Schneeweiss suggested that patients with AA did not seem to have an increased risk of blood clots. However, a more recent 2023 study suggested that patients with alopecia totalis and alopecia universalis may be particularly at risk for venous thromboembolism and therefore the risk may lie more in those with advanced AA forms than just AA as a general group.

Waśkiel-Burnat A et al 2023

Authors of a new study set out to address the issues of venous thromboembolism in alopecia areata. The aim of the author’s study was to compare several markers of venous thromboembolism risk in patients with alopecia areata compared to control groups. These markers included soluble fibrin monomer complex (SFMC), thrombin–antithrombin complex (TATC), and prothrombin fragment 1 +2 (F1 + 2).

MARKERS OF VTE: A CLOSER LOOK AT THREE NOVEL MARKERS

Soluble fibrin monomer complex (SFMC) is a biomarker of fibrin formation and is abnormally elevated in a variety of clinical situations of hypercoagulability. It appears in the bloodstream during the extremely early stage of blood coagulation. Increased SFMC indicates that there has been activation of coagulation and fibrinolysis.

Thrombin–antithrombin complex (TATC) measurements have increasingly been used in humans for diagnosis and assessment of treatment for disorders including DIC, deep vein thrombosis, and pulmonary thromboembolism. TAT is considered to be an effective marker that can detect prothrombotic status earlier than other laboratory testing. Thrombin-antithrombin complex assays detect the protein complex composed of thrombin and antithrombin. The presence of increased TAT is indicative of excess thrombin production.

Prothrombin fragment 1 + 2 (F1+2) is a marker of thrombin generation and hence of coagulation activation. It is released from prothrombin during thrombin formation. It is considered the best marker of in vivo thrombin generation.

The Study

In total, 51 patients with alopecia areata and 26 controls were enrolled in the study. The AA group included 35 women and 16 men; mean age: 38 years and the control group included 18 women and 8 men; mean age: 37 years. The two patient groups were found to not differ with respect to age, sex distribution, or BMI. The serum concentrations of thromboembolism markers were measured using an enzyme-linked immunosorbent assay (ELISA) kit.

Results

Mean SALT score of AA patients was 42. Higher levels of SFMC were detected in patients with alopecia areata compared with the controls [25.66 versus 21.46 ug/ml; p<0.05)]. In addition, a higher level of F1 + 2 was observed in AA patients compared to controls [70150 versus 38620 pg/ml; p<0.001]. TATC levels did not differ between the two groups.

Levels of SFMC and F1+2 were higher in patients with alopecia compared to controls. There were no differences in TATC levels between the two groups

There was no significant correlation was detected among SFMC or F1+ 2 and the Severity of Alopecia Tool (SALT) score, disease duration, or the number of the hair loss episodes. Interestingly, the F1+2 level did correlate with BMI.

Comments

This is interesting and provides further suggestion that patients with AA could be at risk for venous thromboembolism.

There are now several markers of venous thromboembolism that are increased in AA patients compared to controls. These include selectins, D dimer, and now soluble fibrin monomer complex (SFMC) and Prothrombin fragment 1 + 2 (F1+2).

WIth the exception of the 2015 study by Sudnik et al which showed that E- and L-selectin correleated with disease severity, these other biomarker studies did not find an association with severity of disease.

More work is needed to understand what all this means.

The George at al study opens the possibility that VTE risk is more of an issue with advanced forms of AA than milder forms. It’s not clear why the Shakoei et al study did not find a link between D dimer and severity and why this Waśkiel-Burnat A et al. also did not find a correlation with severity. It could be simply because the study was not large enough. But other complex factors may be involved.

REFERENCE

Waśkiel-Burnat A et al. Markers of Venous Thromboembolism Risk in Patients with Alopecia Areata: Is There Anything to Worry about? Dermatol Ther (Heidelb). 2023 Aug;13(8):1847-1855.

Sudnik W et al. The role of selectins in alopecia areata. Postepy Dermatol Alergol. 2015 Feb;32(1):27-32.

Schneeweiss MC et al. Incidence of Venous Thromboembolism in Patients With Dermatologist-Diagnosed Chronic Inflammatory Skin Diseases. JAMA Dermatol. 2021 Jul 1;157(7):805-816.

Shakoei  S et al. Coagulation status in patients with alopecia areata: a cross-sectional study. Ital J Dermatol Venerol. 2021 Oct;156(5):588-592.