ADAMTS13 ACTIVITY and VON Willebrand FACTOR LEVELS IN PATIENTS with Livedoid VASCULOPATHY.

Abstract

5064 Introduction Livedoid vasculopathy is a rare skin disease caused by the extensive formation of microthrombi in dermis vessels, which leads to infarction and ulceration of the epidermis. The pathogenesis of livedoid vasculopathy is unknown, and hypercoagulation states have been implicated. Moreover, success using anticoagulation was reported in some patients. We hypothesized that decreased levels of ADAMTS13 activity and Von Willebrand factor (vWF) levels could contribute to the pathogenesis of local thrombus formation in livedoid vasculopathy. Objective Here we evaluated the levels of ADAMTS13 activity and vWF in patients with livedoid vasculopathy. Patients and methods Fourteen patients (93% female) with livedoid vasculopathy, median age of 41.5 years (22 - 48) were included in the study. All patients were evaluated for the presence of classical acquired and hereditary thrombophilia markers. In addition, vWF antigen levels (Elisa) and activity (collagen binding assays), as well as ADAMTS13 activity (evaluated by residual collagen binding) were evaluated. Results nine patients (64%) were carriers of the MTHFR C677T mutation (6 heterozygous and 3 homozygous); 1 patient was a carrier of factor V Leiden mutation, and 1 patient was a carrier of the FII G20210A mutation. None of the patients presented deficiency of antithrombin, protein C or S, and antiphospholipid antibodies were not identified in our study population. ADAMTS13 and VWF activities were normal in all patients. Median vWF antigen was 120.5U/dl (reference value of 40.0 - 232.0%), and vWF activity was 102.3% (reference value of 45.5 - 203.7%). ADAMTS13 activity was 138.9% (reference value of 56.0 - 227.2 %). Two patients had a history of thromboembolic diseases: one patient with 2 strokes and one patient with central retinal artery occlusion. Conclusion We show here that ADAMTS13 activity and vWF levels are not altered in patients with livedoid vasculopathy. The MTHFR C677T mutation is frequent in patients with livedoid vasculopathy but quantification of homocysteine levels is necessary to consider any relationship with this disease. Disclosures No relevant conflicts of interest to declare.

Livedoid vasculopathy and its association with genetic variants: A systematic review

“…Eighty‐five LV patients from 15 studies or case reports were evaluated for Prothrombin G20210A, 4 , 5 , 14 , 15 , 16 , 18 , 21 , 22 , 23 , 24 , 25 , 27 , 28 , 29 , 31 while patients from another three studies were excluded because of vague descriptions of heterozygosity or homozygosity. 8 , 9 , 10 The total carrier rate of Prothrombin G20210A was 10.59% (9/85), which was the lowest carrier rate of the six SNPs assessed. All the LV patients with Prothrombin G20210A displayed a heterozygous GA genotype (9/85); no homozygous AA carrier was identified (0/85).…”

“…Eighty‐five LV patients from 15 studies or case reports were evaluated for Prothrombin G20210A, 4,5,14‐16,18,21‐25,27‐29,31 while patients from another three studies were excluded because of vague descriptions of heterozygosity or homozygosity 8‐10 . The total carrier rate of Prothrombin G20210A was 10.59% (9/85), which was the lowest carrier rate of the six SNPs assessed.…”

“…After the extensive literature search, 53 articles were found in PubMed and Embase databases that concern genetic variants in LV patients. By carefully reviewing the full texts of these 53 articles, 30 were enrolled that complied with the inclusion and exclusion criteria (Table 1 ) 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 . A total of 265 patients, of whom 78 were male (29.43%) and 187 were female (70.57%) giving a female to male ratio of 2.4:1, were tested for at least one out of the following six genetic variants, MTHFR C677T and A1298C, PAI‐1 ‐675 4G/5G and A844G, and Prothrombin G20210A and Factor V G1691A.…”

“…Thirteen articles presented LV patients that were examined for MTHFR C677T, 4 , 5 , 6 , 9 , 10 , 11 , 15 , 16 , 23 , 25 , 26 , 30 , 32 although one article referred vaguely to its heterozygosity or homozygosity. 9 A total of 129 patients were tested for MTHFR C677T, of which 46 had the heterozygous CT genotype (35.66%) and 25 had the homozygous TT genotype (19.38%).…”

“…The total carrier rate of Factor V G1691A (14.07%) in LV patients was the second lowest among the tested SNPs. From 23 articles, 4 , 5 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 27 , 31 , 32 , 33 135 LV patients were tested. In one study 10 heterozygosity or homozygosity was not clearly stated; however, the remaining studies showed 19 patients to have the heterozygous GA genotype and no patients to have the homozygous AA genotype (0/135).…”