Tranexamic acid reduces inflammation, edema and burn wound conversion in a rodent model.

Burn wound conversion is the observed process where superficial partial thickness burns convert into deep partial or full thickness burn injuries. This conversion process often involves surgical excision to achieve timely wound healing. Unfortunately, the pathophysiology of this phenomenon is multifactorial and poorly understood. Thus, a therapeutic intervention that may prevent secondary progression and cell death in burn-injured tissue is desirable. Recent work by our group and others has established that tranexamic acid (TXA) has significant anti-inflammatory properties in addition to its well-known anti-fibrinolytic effects. This study investigates TXA as a novel therapeutic treatment to mitigate burn wound conversion and reduce systemic inflammation. Sprague-Dawley rats were subjected to a hot comb burn contact injury. A subset of animals underwent a similar comb burn with an adjacent 30%TBSA contact injury. The interspaces represent the ischemic zones simulating the zone of stasis. The treatment group received injections of TXA (100 mg/kg) immediately after injury and once daily until euthanasia. Animals were harvested for analyses at 6 h and 7 days after injury. Full-thickness biopsies from the ischemic zones and lung tissue were assessed with established histological techniques. Plasma was collected for measurement of damage associated molecular patterns (DAMPs), and liver samples were used to study inflammatory cytokines expression. Treatment with TXA was associated with reduced burn wound conversion and decreased burn-induced systemic inflammatory response syndrome (SIRS). Lung inflammation and capillary leak were also significantly reduced in TXA treated animals. Future research will elucidate the underlying anti-inflammatory properties of TXA responsible for these findings.

Protocoled thrombolytic therapy for frostbite improves phalangeal salvage rates.

BACKGROUND: Frostbite is a cold injury that has the potential to cause considerable morbidity and long-term disability. Despite the complexity of these patients, diagnostic and treatment practices lack standardization. Thrombolytic therapy has emerged as a promising treatment modality, demonstrating impressive digit salvage rates. We review our experience with thrombolytic therapy for severe upper extremity frostbite. METHODS: Retrospective data on all frostbite patients evaluated at our institution from December 2017 to March 2018 was collected. A subgroup of patients with severe frostbite treated with intra-arterial thrombolytic therapy (IATT) were analysed. RESULTS: Of the 17 frostbite patients treated at our institution, 14 (82%) were male and the median age was 31 (range: 19-73). Substance misuse was involved in a majority of the cases (58.8%). Five (29.4%) patients with severe frostbite met inclusion criteria for IATT and the remaining patients were treated conservatively. Angiography demonstrated a 74.5% improvement in perfusion after tissue plasminogen activator thrombolysis. When comparing phalanges at risk on initial angiography to phalanges undergoing amputation, the phalangeal salvage rate was 83.3% and the digit salvage rate was 80%. Complications associated with IATT included groin hematoma, pseudoaneurysm and retroperitoneal hematoma. CONCLUSIONS: Thrombolytic therapy has the potential to greatly improve limb salvage and functional recovery after severe frostbite when treated at an institution that can offer comprehensive, protocoled thrombolytic therapy. A multi-center prospective study is warranted to elucidate the optimal treatment strategy in severe frostbite.

Tranexamic acid suppresses the release of mitochondrial DAMPs and reduces lung inflammation in a murine burn model.

BACKGROUND: Severe burn injuries are known to initiate a profound systemic inflammatory response (SIRS) that may lead to burn shock and other SIRS-related complications. Damage-associated molecular patterns (DAMPs) are important early signaling molecules that initiate SIRS after burn injury. Previous work in a rodent model has shown that application of a topical immune modulator (p38MAPK inhibitor) applied directly to the burn wound decreases cytokine expression, reduces pulmonary inflammation and edema. Our group has demonstrated that tranexamic acid (TXA)-in addition to its use as an antifibrinolytic-has cell protective in vitro effects. We hypothesized that administration of TXA after burn injury would attenuate DAMP release and reduce lung inflammation. METHODS: C57/BL6 male mice underwent a 40% Total Body Surface Area (TBSA) scald burn. Sham animals underwent the same procedure in room temperature water. One treatment group received the topical application of p38MAPK inhibitor after burn injury. The other treatment group received an intraperitoneal administration of TXA after burn injury. Animals were sacrificed at 5 hours. Plasma was collected by cardiac puncture. MtDNA levels in plasma were determined by quantitative Polymerase Chain Reaction (qPCR). Syndecan-1 levels in plasma were measured by ELISA. Lungs were harvested, fixed, and paraffin-embedded. Sections of lungs were stained for antigen to detect macrophages. RESULTS: Topical p38MAPK inhibitor and TXA significantly attenuated mtDNA release. Both TXA and the topical p38MAPK inhibitor reduced lung inflammation as represented by decreased macrophage infiltration. Syndecan-1 levels showed no difference between burn and treatment groups. CONCLUSION: Both p38 MAPK inhibitor and TXA demonstrated the ability to attenuate burn-induced DAMP release and lung inflammation. Beyond its role as an antifibrinolytic, TXA may have significant anti-inflammatory effects pertinent to burn resuscitation. Further study is required; however, TXA may be a useful adjunct in burn resuscitation.