Documento multidisciplinar de consenso sobre el manejo de la hemorragia masiva. Primera actualización 2023 (documento HEMOMAS-II) / Multidisciplinary consensus document on the management of massive haemorrhage. First update 2023 (document HEMOMAS-II)

El presente documento supone una puesta al día del documento multidisciplinar HEMOMAS, publicado en el año 2016 con el aval de las Sociedades Científicas Españolas de Anestesiología y Reanimación (SEDAR), Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y de Trombosis y Hemostasia (SETH). El objetivo de este documento fue revisar y actualizar las recomendaciones existentes sobre el manejo de la hemorragia masiva (HM). Se siguió una metodología basada en elementos del método ADAPTE (búsqueda y adaptación de guías publicadas en el ámbito específico de la HM desde 2014, más búsqueda bibliográfica en PubMed y EMBASE desde enero-2014 hasta junio-2021). Tras la revisión de nueve guías y 207 artículos seleccionados, se actualizaron las 47 recomendaciones existentes en el artículo original, manteniendo, suprimiendo o modificando cada una de ellas y sus grados de recomendación y evidencia. Consensuadamente, los autores aprobaron la redacción final del artículo y las 41 recomendaciones resultantes (AU)

This document is an update of the multidisciplinary document HEMOMAS, published in 2016 with the endorsement of the Spanish Scientific Societies of Anaesthesiology (SEDAR), Intensive Care (SEMICYUC) and Thrombosis and Haemostasis (SETH). The aim of this document was to review and update existing recommendations on the management of massive haemorrhage. The methodology of the update was based on several elements of the ADAPTE method by searching and adapting guidelines published in the specific field of massive bleeding since 2014, plus a literature search performed in PubMed and EMBASE from January 2014 to June 2021. Based on the review of 9 guidelines and 207 selected articles, the 47 recommendations in the original article were reviewed, maintaining, deleting, or modifying each of them and the accompanying grades of recommendation and evidence. Following a consensus process, the final wording of the article and the resulting 41 recommendations were approved by all authors (AU)

Successful immune tolerance induction with a plasma-derived FVIII concentrate and intravenous immunoglobulins in a pediatric patient with congenital severe hemophilia A and poor prognostic factors.

We present the case of a pediatric patient born in July 1991, diagnosed with severe hemophilia A at 8 months of life after a hemarthrosis. He was treated with regular factor replacement therapy on-demand until an inhibitor was detected (1.75-2.5 BU) at the age of 6. The patient started an immunotolerance induction (ITI) program, which was discontinued 3 months later because of parental decision based on inhibitor persistence (3.75-6.75 BU). On-demand treatment with recombinant activated FVII in bleeding episodes was applied. Titer peaked 13 months later (37 BU). On May 2003 (age 11), rescue ITI with plasma-derived FVIII (Fanhdi, 100 IU/kg per 24 h daily) and intravenous immunoglobulin (IVIg) (Flebogamma, 1 g/kg per 24 h for 2 days every 3 weeks) was started. Inhibitor eradication was achieved after 16 months of ITI. The patient continued with FVIII+IVIg treatment for 3 additional months when he was switched to FVIII prophylaxis (40 IU/kg 3 times a week). At present, the patient is inhibitor-free.

Organellar proteomics of human platelet dense granules reveals that 14-3-3zeta is a granule protein related to atherosclerosis.

Dense granules, a type of platelet secretory organelle, are known to accumulate high concentrations of small molecules such as calcium, adenine nucleotides, serotonin, pyrophosphate, and polyphosphate. Protein composition of these granules has been obscure, however. In this paper, we use proteomics techniques to describe, for the first time, the soluble protein composition of platelet dense granules. We have isolated highly enriched human platelet dense granule fractions that have been analyzed using two proteomics methods. Using this approach, we have identified 40 proteins, and most of them, such as actin-associated proteins, glycolytic enzymes, and regulatory proteins, have not previously been related to the organelle. We have focused our efforts on studying 14-3-3zeta, a member of a conserved family of proteins that interact with hundreds of different proteins. We have demonstrated that 14-3-3zeta is localized mostly on dense granules and that it is secreted after platelet activation. As some proteins secreted from activated platelets could promote the development of atherosclerosis and thrombosis, we have studied the expression of 14-3-3zeta in sections of human abdominal aorta of patients with aneurysm, identifying it at the atherosclerotic plaques. Together, our results reveal new details of the composition of the platelet dense granule and suggest an extracellular function for 14-3-3zeta associated with atherosclerosis.

Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals.

OBJECTIVE: We carried out a prospective analysis of clinical and analytical findings in individuals with antiphospholipid antibodies (aPL). METHODS: We prospectively studied 404 individuals, classified in 2 groups: (1) patients with primary or secondary antiphospholipid syndrome (APS, n = 226); and (2) asymptomatic carriers of aPL (n = 178). Patients with APS and thrombosis were treated with dicumarin, and an international normalized ratio around 3.0 (range 2.5-3.5) was targeted. Asymptomatic carriers were not treated, but specific prophylaxis with low molecular weight heparin or aspirin was prescribed for the periods when individuals were at increased risk of thrombosis. Both groups of individuals were followed up at semester intervals for 36 months. RESULTS: Patients with APS presented with venous (n = 106, 46.9%) and/or arterial (n = 70. 31%) thrombosis or fetal loss (n = 58 out of 112 women of fertility age, 51.8%). At the time of the first thrombotic event, 50.0% of patients with APS had coincident risk factors for thrombosis (previous surgery and prolonged immobilization were significantly associated with venous thrombosis, and hypercholesterolemia and arterial hypertension with arterial thrombosis). Eighteen patients with APS died during the study period. Recurrence of thrombosis in patients with APS was linked to insufficient anticoagulation. During the followup, no episode of thrombosis was detected in any asymptomatic carrier. The proportion of subjects with aPL was similar in patients and in asymptomatic carriers. The proportion of subjects with aPL decreased during the followup, in both patients and carriers. CONCLUSION: Differences between patients and asymptomatic carriers with aPL are at least partially dependent on the proportion of coincident vascular risk factors. The decline in aPL during the followup defines a subgroup in which an anticoagulation suppression assay could be tried.