OBJECTIVE: To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference.
METHODS: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.
METHODS: Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs).
METHODS: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.
RESULTS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented.
CONCLUSIONS: Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

OBJECTIVE: There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert\'s consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth.
METHODS: Systematic review and three-stage modified Delphi expert consensus.
METHODS: International.
METHODS: Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance.
METHODS: Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth.
RESULTS: Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman\'s haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman\'s haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach.
CONCLUSIONS: These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step.

The use of strategies to reduce blood loss and transfusions is essential in the treatment of surgical patients, including in complex cardiac surgeries and those that use cardiopulmonary bypass. Antifibrinolytics, such as epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), are widely used in these procedures, as well as in other types of surgeries. These medicines are included in the World Health Organization (WHO) list of \'essential medicines\'. Scientific evidence demonstrates the effectiveness of EACA in reducing bleeding and the need for transfusions in heart surgery. EACA is highly recommended for use in heart surgery by the American Society of Anesthesiology Task Force on Perioperative Blood Management. Regarding the safety of EACA, there is no robust evidence of any significant thrombotic potential. TXA has also been shown to be effective in reducing the use of blood transfusions in cardiac and non-cardiac surgeries and is considered safer than other antifibrinolytic agents. There is no evidence of any increased risk of thromboembolic events with TXA, but doses greater than 2 g per day have been associated with an increased risk of seizures. It is also important to adjust the dose in patients with renal impairment. In conclusion, antifibrinolytics, such as EACA and TXA, are effective in reducing blood loss and transfusion use in cardiac and non-cardiac surgeries, without causing serious adverse effects.

The management of patients with critical bleeding requires a multidisciplinary approach to achieve haemostasis, optimise physiology, and guide blood component use. The 2011 Patient blood management guidelines: module 1 - critical bleeding/massive transfusion were updated and published. Systematic reviews were conducted for pre-specified research questions, and recommendations were based on meta-analyses of included studies.
The critical bleeding/massive transfusion guideline includes seven recommendations and 11 good practice statements addressing: major haemorrhage protocols (MHPs) facilitating a multidisciplinary approach to haemorrhage control, correction of coagulopathy and normalisation of physiological derangement; measurement of physiological, biochemical and metabolic parameters in critical bleeding/massive transfusion; the optimal ratio of red blood cells to other blood components; the use of tranexamic acid; viscoelastic haemostatic assays; and cell salvage.
The new guideline recommends MHPs be established as standard of care in all institutions managing patients with critical bleeding. In addition to routine physiological markers, the new guideline recommends temperature, biochemistry and coagulation profiles be measured early and frequently, providing parameters that define critical derangements. Ratio-based MHPs should include no fewer than four units of fresh frozen plasma and one adult unit of platelets for every eight units of red blood cells. In the setting of trauma and obstetric haemorrhage, administration of tranexamic acid within three hours of bleeding onset is recommended. The use of recombinant activated factor VII (rFVIIa) is not recommended. There was insufficient evidence to make recommendations on the use of viscoelastic haemostatic assays or cell salvage as part of MHPs.

UNASSIGNED: Peripartum haemorrhage (PPH) is a potentially life-threatening complication. Although still rare, the incidence of peripartal haemorrhage is rising in industrialised countries and refractory bleeding remains among the leading causes of death in the peripartal period.
UNASSIGNED: The interdisciplinary German, Austrian, and Swiss guideline on \"Peripartum Haemorrhage: Diagnostics and Therapies\" has reviewed the evidence for the diagnostics and medical, angiographic, haemostatic, and surgical treatment and published an update in September 2022 . This article reviews the updated recommendations regarding the early diagnosis and haemostatic treatment of PPH. Keystones of the guideline recommendations are the early diagnosis of the bleeding by measuring blood loss using calibrated collector bags, the development of a multidisciplinary treatment algorithm adapted to the severity of bleeding, and the given infrastructural conditions of each obstetric unit, the early and escalating use of uterotonics, the therapeutic, instead of preventative, use of tranexamic acid, the early diagnostics of progressive deficiencies of coagulation factors or platelets to facilitate a tailored and guided haemostatic treatment with coagulation factors, platelets as well as packed red blood cells and fresh frozen plasma when a massive transfusion is required.
UNASSIGNED: Essential for the effective and safe treatment of PPH is the timely diagnosis. The diagnosis of PPH requires the measurement rather than estimation of blood loss. Successful treatment of PPH consists of a multidisciplinary approach involving surgical and haemostatic treatments to stop the bleeding. Haemostatic treatment of PPH starts early after diagnosis and combines tranexamic acid, an initially ratio-driven transfusion with RBC:plasma:PC = 4:4:1 (when using pooled or apheresis PC) and finally a goal-directed substitution with coagulation factor concentrates for proven deficiencies. Early monitoring of coagulation either by standard parameters or viscoelastic methods facilitates goal-directed haemostatic treatment.

BACKGROUND: Prehospital (PH) tranexamic acid (TXA) improves survival from trauma haemorrhage. Injury mechanism, physiology, and sex demographics vary with patient age. The authors hypothesised that these factors influence TXA guideline compliance and examined national trends in PH use to identify any systematic biases in bleeding management.
METHODS: The UK Trauma Audit and Research Network data for TXA eligible patients admitted to major trauma centres were divided into two cohorts: 2013-2015 ( n =32 072) and 2017-2019 ( n =14 974). Patients were stratified by PH, emergency department or no TXA use. Logistic regression models explored interaction between PH variables and TXA administration. Results are presented as odds ratios with a 95% CI.
RESULTS: PH TXA use increased from 8% to 27% over time ( P <0.001). Only 3% of eligible patients who fell less than 2 m received PH TXA versus 63% with penetrating injuries ( P <0.001). Older patients eligible for PH TXA were less likely to receive it compared to younger patients [≥65 years old: 590 (13%) vs. <65 years old: 3361 (33%), P <0.001]. There was a significant interaction between age and sex with fewer older women receiving PH TXA. In shocked patients, one third of females compared to a fifth of men did not receive TXA ( P <0.001). There was a decrease in PH TXA use as age increased ( P <0.001).
CONCLUSIONS: Despite a threefold increase in use, treatment guidance for PH TXA is not universally applied. Older people, women, and patients with low energy injury mechanisms appear to be systematically under treated. Training and education for PH providers should address these potential treatment biases.

Introduction There is ambiguity regarding usage of tranexamic acid for melasma in India, be it in its pre-administration evaluation, administration route, dosing or monitoring. Hence, we conducted this study to understand various tranexamic-acid prescribing patterns and provide practical guidelines. Materials and methods A Google-form-based questionnaire (25-questions) was prepared based on the key areas identified by experts from the Pigmentary Disorders Society, India and circulated to practicing dermatologists across the country. In rounds 2 and 3, the questionnaire was re-presented to the same group of experts and their opinions were sought. The results of the practitioners\' survey were denoted graphically alongside, to guide them. Consensus was deemed when at least 80% of respondents chose an option. Results The members agreed that history pertaining to risk factors for thromboembolism, cardiovascular and menstrual disorders should be sought in patients being started on oral tranexamic-acid. Baseline coagulation profile should be ordered in all patients prior to tranexamic-acid and more exhaustive investigations such as complete blood count, liver function test, protein C and S in patients with high risk of thromboembolism. The preferred oral dose was 250 mg orally twice daily, which can be used alone or in combination with topical hydroquinone, kojic acid and sunscreen. Repeated dosing of tranexamic-acid may be required for those relapsing with melasma following initial tranexamic-acid discontinuation. Coagulation profile should ideally be repeated at three monthly intervals during follow-up, especially in patients with clinically higher risk of thromboembolism. Treatment can be stopped abruptly post improvement and no tapering is required. Limitation This study is limited by the fact that open-ended questions were limited to the first general survey round. Conclusion Oral tranexamic-acid provides a valuable treatment option for melasma. Frequent courses of therapy may be required to sustain results and a vigilant watch is recommended for hypercoagulable states during the course of therapy.

Hereditary angioedema (HAE) is an uncommon disorder characterized clinically by recurrent episodes of nonitchy subcutaneous and/or submucosal swellings. The estimated prevalence of HAE is ~ 1: 10,000 to 1: 50,000. There are no prevalence data from India, however, estimates suggest that there are 27,000 to 135,000 patients with HAE in India at present. The majority of these, however, remain undiagnosed. Replacement of plasma-derived or recombinant C1-esterase inhibitor (C1-INH) protein, administered intravenously, is the treatment of choice during the management of acute episodes of angioedema (i.e., \"on-demand treatment\") and is also useful for short-term prophylaxis (STP) and long-term prophylaxis (LTP). This has been found to be effective and safe even in young children and during pregnancy. Until recently, none of the first-line treatment options were available for \"on-demand treatment,\" STP or LTP in India. As a result, physicians had to use fresh frozen plasma for both \"on-demand treatment\" and STP. For LTP, attenuated androgens (danazol or stanozolol) and/or tranexamic acid were commonly used. These drugs have been reported to be useful for LTP but are associated with a significant risk of adverse effects. Intravenous pd-C1-INH, the first-line treatment option, is now available in India. However, because there is no universal health insurance, access to pd-C1-INH is a significant challenge. HAE Society of India has developed these consensus guidelines for India and other resource-constrained settings where plasma-derived C1-INH therapy is the only available first-line treatment option for the management of HAE and diagnostic facilities are limited. These guidelines have been developed because it may not be possible for all patients to access the recommended therapy and at the recommended doses as suggested by the international guidelines. Moreover, it may not be feasible to follow the evaluation algorithm suggested by the international guidelines.

The S3 guideline on the treatment of patients with severe/multiple injuries by the German Association of the Scientific Medical Societies was updated between 2020 and 2022. This article describes the essence of the new chapter \"Stop the bleed-prehospital\" and the revised chapter \"Coagulation management and volume therapy\".

Because of its complex pathogenesis, chronicity, and high rates of recurrence, melasma is regarded as a challenging skin disorder. Topical treatments are often offered as first-line therapy. However, many patients are unaware that melasma is recurrent and requires long-term management. Hydroquinone is effective for controlling relapses and has become the standard of care for melasma in many countries. Nonetheless, it is limited by its side effect profile. Certain patient profiles who have had prior therapy and/or are refractory to treatment may be offered an alternative, that is topical tranexamic acid (TXA) alone or in combination with other modalities. This review provides a summary of current evidence on topical TXA as a treatment for certain case profiles. This paper aims to fill knowledge gaps in terms of currently available options, highlighting the role of topical TXA alone or in combination with other active ingredients (ie, topical TXA 2% with patented delivery technology). J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7104 Citation: Desai SR, Chan LC, Handog E, et al. Optimizing melasma management with topical tranexamic acid: An expert consensus. J Drugs Dermatol. 2023;22(4):386-392. doi:10.36849/JDD.7104.