Subcutaneous Injection of Tranexamic Acid to Reduce Bleeding During Dermatologic Surgery: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: Topical application, oral, and IV injection of tranexamic acid (TXA) have been used to reduce surgical bleeding. OBJECTIVE: To evaluate the safety and efficacy of TXA injected subcutaneously to reduce bleeding during dermatologic surgery. METHODS: In this double-blinded, placebo-controlled, randomized prospective study, 131 patients were randomized to subcutaneous injection of lidocaine 2% diluted 1:1 with either saline (placebo) or TXA 100 mg/1 mL before surgery. Before the second stage or closure, size measurements of bloodstain impregnation on Telfa and surgical wound size were recorded and analyzed using mixed-effects linear regression. Subjective evaluation of hemostasis was performed using 4-point scale grading and analyzed using Fischer's exact test. RESULTS: One hundred twenty-seven patients completed the study. The bloodstain to surgical wound size ratio was smaller in the TXA group (1.77) compared with the placebo group (2.49) (p < .001). An improved effect of TXA on bleeding was observed in the subgroup of patients receiving anticoagulants (mean difference; 95% confidence interval; -0.83; -1.20 to -0.46 p < .001). The subjective hemostasis assessment was significantly better in the TXA group overall (p = .043) and anticoagulant subgroup (p = .001) compared with the placebo group. CONCLUSION: Subcutaneous injection of TXA was safe, reduced bleeding during dermatologic surgery, and particularly effective for patients receiving anticoagulation treatment.

Subcutaneous tranexamic acid in upper eyelid blepharoplasty: a prospective randomized pilot study.

OBJECTIVE: Postoperative ecchymoses or hematomas can prolong healing from surgery, and a search for locally administered agents that decrease bleeding is warranted. The objective of this study is to evaluate whether preoperative subcutaneous injection of tranexamic acid (TXA) reduces intra- and postoperative bleeding or ecchymoses in skin-only upper eyelid blepharoplasty surgery. DESIGN: This is a prospective randomized, double-blind, controlled study. PARTICIPANTS: We included 34 consecutive patients who were referred to an upper eyelid blepharoplasty surgery in our institution. METHODS: The patients were equally randomized to a preoperative local injection of lidocaine mixed with either TXA or normal saline. All patients stopped antiaggregates 1 week before surgery. All surgeries were performed by a single surgeon who was unaware of group assignment. Total surgical time, cumulative time of cautery use, blood loss, the surgeon's assessment of bleeding extent, pain level reported by the patient, periocular ecchymoses during the first postoperative week, and time for patient's return to normal daily activity were recorded. RESULTS: There was a trend toward smaller ecchymoses in the TXA group compared with the placebo group on the seventh day (p = 0.072). There were no group differences in total surgery time, cumulative cautery time, net blood weight in surgical pads, patient-reported pain level, surgeon's assessment of hemostasis, or periocular ecchymosis size on the first postoperative day. CONCLUSIONS: Subcutaneous TXA was associated with similar intra- and postoperative hemorrhage in upper eyelid blepharoplasty compared with placebo. The effect of TXA in patients who did not stop antiaggregate use before surgery warrants further study.

Model of trauma-induced coagulopathy including hemodilution, fibrinolysis, acidosis, and hypothermia: Impact on blood coagulation and platelet function.

BACKGROUND: Trauma-induced coagulopathy (TIC) is commonly seen among patients with severe injury. The dynamic process of TIC is characterized by variability of the features of the disease. METHODS: A model of TIC was created. Hemodilution was produced by mixing the blood with 40% Tris/saline solution, fibrinolysis by treating the blood with 160 ng/mL tPA, acidosis by adding 1.2 mg/mL lactic acid achieving pH 7.0 to 7.1, and hypothermia by running the assay at 31°C. Intact blood tested at 37°C served as control. Clot formation was evaluated using rotation thromboelastometry. Platelet adhesion and aggregation were assayed at a shear rate of 1800 s(-) using Impact-R device. RESULTS: Clotting time was not affected by any of the TIC constituents used. Clotting initiation was reduced by hemodilution and further reduced by additive hypothermia. The propagation phase of blood clotting was reduced by hemodilution, further reduced by additive hypothermia, and maximally reduced if additionally combined with fibrinolysis. No effect of fibrinolysis on clot propagation was observed at 37°C. Maximum clot firmness was reduced by hemodilution, further reduced by additive fibrinolysis, and maximally reduced if additionally combined with hypothermia. No effect of hypothermia on clot strength was observed in the absence of fibrinolysis. Platelet adhesion (percentage of surface coverage) and aggregation (aggregate size) under flow condition were reduced by hemodilution and further reduced by additive acidosis. Introduction of tPA to diluted blood had no effect on platelet function. CONCLUSION: The study revealed a differential effect of TIC constituents-hemodilution, hypothermia, fibrinolysis, and acidosis-on clot formation and platelet function. The effect of one factor may influence that of another factor. These data may be helpful to better understand the pathogenesis of TIC and to elaborate an individually tailored treatment strategy. LEVEL OF EVIDENCE: A new model of TIC is created. Contribution of various constituents to pathogenesis of TIC and their interactions are evaluated.

Topical Hemostatic-Anesthetic Solution to Reduce Bleeding During Mohs Micrographic Surgery: A Case Control Study.

BACKGROUND: Between stages of Mohs micrographic surgery, the wound is dressed and the patient waits for the histopathological results.
OBJECTIVE: To investigate the efficacy of a hemostatic-anesthetic solution-impregnated gauze in decreasing bleeding between Mohs stages.
MATERIALS AND METHODS: Twenty patients were treated with a hemostatic-anesthetic solution composed of tranexamic acid, adrenaline, and lidocaine (TAL), and 20 others were treated with a saline solution for control. At the second Mohs stage, size measurements of the blood stain on a Telfa pad and the defect were recorded. The Rotation Thromboelastometry Method (ROTEM) was used to investigate a possible effect of lidocaine and adrenaline on the clot stability induced by tranexamic acid.
RESULTS: The ratio of blood stain size to Mohs defect size in the hemostatic anesthetic solution group was 1:1.47, whereas the ratio in the control saline group was 1:3.37 (P<.001). Results of the ROTEM test showed that lidocaine and adrenaline did not interfere with the effect of tranexamic acid on clot formation and stability.
CONCLUSION: The application of gauze impregnated with tranexamic acid, adrenaline, and lidocaine on a surgical wound may be effective in reducing bleeding between Mohs stages.

J Drugs Dermatol. 2016;15(7):851-855.

Chitosan-based dressing for the treatment of external/accessible bleedings in children with bleeding tendency.

INTRODUCTION: Bleeding episodes in patients with congenital or acquired bleeding disorders are usually managed with factor concentrates or blood products. However, external and accessible bleeds may effectively be managed with topical hemostasis. MATERIALS AND METHODS: After the application of the Hemcon, a Food and Drug Administration-approved chitosan-based hemostatic dressing was used as the "last resort" to successfully control external bleeds in 2 patients with severe bleeding disorders. We describe a single-center experience with this dressing, including its use in pediatric patients as the first mode of therapy. RESULTS: A total of 5 patients (median age 2 y) with severe bleeding disorders were treated with topical chitosan-based dressing for a total of 6 bleeding episodes. The dressing was used either after the failure of extensive systemic therapy or as the first choice of treatment. In 4 of the 6 episodes, bleeding ceased immediately alleviating the need for systemic therapy. There was no rebleeding after the removal of the dressing and no adverse events or local skin reactions were recorded. CONCLUSION: Hemostatic dressings, such as the chitosan, should be encouraged for the treatment of external/accessible bleeds, especially among the pediatric patients with bleeding tendency.

A novel role for factor VIII and thrombin/PAR1 in regulating hematopoiesis and its interplay with the bone structure.

Analysis of hematopoietic stem cells (HSCs) in factor VIII knockout (FVIIIKO) mice revealed a novel regulatory role for the coagulation cascade in hematopoiesis. Thus, HSCs in FVIIIKO mice had reduced proportions of CD34(low) cells within Lin(-)Sca(+)Kit(+) progenitors, and exhibited reduced long-term repopulating capacity as well as hyper granulocyte-colony-stimulating factor (G-CSF)-induced mobilization. This disregulation of HSCs is likely caused by reduced levels of thrombin, and is associated with altered protease-activated receptor 1 (PAR1) signaling, as PAR1 KO mice also exhibited enhanced G-CSF-induced mobilization. Analysis of reciprocal bone marrow (BM) chimera (FVIIIKO BM into wild-type recipients and vice versa) and the detection of PAR1 expression on stromal elements indicates that this phenotype is likely controlled by stromal elements. Micro-computed tomography analysis of distal tibia metaphyses also revealed for the first time a major impact of the FVIII/thrombin/PAR1 axis on the dynamic bone structure, showing reduced bone:tissue volume ratio and trabecular number in FVIIIKO and PAR1KO mice. Taken together, these results show a critical and novel role for the coagulation cascade, mediated in part by thrombin-PAR1 interaction, and regulates HSC maintenance and a reciprocal interplay between HSCs and the dynamic bone structure.

The in vivo effect of fibrinogen and factor XIII on clot formation and fibrinolysis in Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia (GT) is characterized by increased bleeding risk. The treatment options in GT are limited. The aim of this study was to test the effect of GT blood supplementation with fibrinogen and factor XIII on thrombin generation, blood clotting, and fibrinolysis. Whole blood samples of GT patients and normal donors treated with eptifibatide (GT model) were subjected to clotting by CaCl(2) and tissue factor. Thrombin generation was measured in platelet-rich plasma. Clot formation and tPA-induced fibrinolysis were evaluated in whole blood by rotation thromboelastometry (ROTEM). Blood was supplemented with fibrinogen (3 g/L) and/or FXIII (2 IU/mL). Thrombin generation analysis of blood derived from GT model and GT patients revealed decreased endogenous thrombin potential and peak height and extended lag time compared to control. However, this method was not sensitive to blood spiking with fibrinogen and FXIII. ROTEM revealed lower maximum clot firmness (MCF) and area under curve (AUC) in the blood of GT model and GT patients. In the absence of exogenous tPA, blood spiking with fibrinogen markedly enhanced clot quality while FXIII had no effect. Combination of fibrinogen and FXIII did not add to the effect of fibrinogen. In contrast, by the addition of tPA, both fibrinogen and FXIII separately and, to more extent, in combination enhanced clot quality as well as resistance against tPA-induced fibrinolysis (increasing MCF, AUC, and lysis onset time). In conclusion, fibrinogen and FXIII exerted stimulation of blood clotting and inhibition of fibrinolysis. Treating normal blood with eptifibatide mimics the changes of coagulopathy in GT blood.

Thrombophilic factors in idiopathic intracranial hypertension: a report of 51 patients and a meta-analysis.

Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell's viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-beta2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68-12.60)], similar to the association with high factor VIII [OR = 16.17 (2.87-91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR = 6.91 (2.28-20.91)], and high lipoprotein (a) [LP(a)] [OR = 3.54 (1.54-8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH.