Neither Antiplatelet nor Anticoagulant Therapy Increases Graft Failure after Split-thickness Skin Grafting.

Split-thickness skin grafts (STSG) are an effective modality for lower extremity wound coverage. Many patients in the highly comorbid chronic wound population present with cardiovascular disease requiring chronic antiplatelet or anticoagulant therapy, theoretically increasing risk for bleeding complications, donor site morbidity, and poor graft take. Some surgeons advocate temporary cessation of antithrombotic therapy, which may increase cardiovascular risk. The objective of this study was to examine the effects of anticoagulation use on STSG outcomes. Methods: All patients receiving STSGs for lower extremity wounds from 2014 to 2016 at a single institution were retrospectively reviewed. Successful grafts were defined as greater than 99.5% wound coverage. Patients were divided into two groups: anticoagulation/antiplatelet or no anticoagulation/antiplatelet. Continuous variables were described by means and SDs and analyzed using student's t-test. Categorical variables were described by frequencies and percentages and analyzed using Chi-square or Fisher exact tests as appropriate. Results: In total, 231 wounds were identified among 189 patients; 124 patients were receiving at least one antiplatelet/anticoagulant at time of grafting. Three hematomas were reported during 30 days of follow-up; there was no significant difference between groups (P > 0.05). Anticoagulation/antiplatelet therapy in the perioperative period had no significant impact on STSG take and overall healing. Conclusions: The findings from this study demonstrate that administration of anticoagulant/antiplatelet agents in the perioperative period does not increase the risk of skin graft failure. Based on these findings, STSG can be performed without cessation of anticoagulation or antiplatelet therapy.

Loss of ß-PIX inhibits focal adhesion disassembly and promotes keratinocyte motility via myosin light chain activation.

During healing of the skin, the cytoskeleton of keratinocytes and their matrix adhesions, including focal adhesions (FAs), undergo reorganization. These changes are coordinated by small GTPases and their regulators, including the guanine nucleotide exchange factor ß-PIX (also known as ARHGEF7). In fibroblasts, ß-PIX activates small GTPases, thereby enhancing migration. In keratinocytes in vitro, ß-PIX localizes to FAs. To study ß-PIX functions, we generated ß-PIX knockdown keratinocytes. During wound closure of ß-PIX knockdown cell monolayers, disassembly of FAs is impaired, and their number and size are increased. In addition, in the ß-PIX knockdown cells, phosphorylated myosin light chain (MLC; also known as MYL2) is present not only in the leading edge of cells at the wound front, but also in the cells following the front, while p21-activated kinase 2 (PAK2), a regulator of MLC kinase (MYLK), is mislocalized. Inhibition or depletion of MYLK restores FA distribution in ß-PIX knockdown cells. Traction forces generated by ß-PIX knockdown cells are increased relative to those in control cells, a result consistent with an unexpected enhancement in the migration of single ß-PIX knockdown cells and monolayers of such cells. We propose that targeting ß-PIX might be a means of promoting epithelialization of wounds in vivo.