Déficit Combinado de Proteína C y S de la Coagulación en Paciente Joven como Causa de Enfermedad Cerebrovascular Isquémica, a Propósito de 1 caso Clínico

Protein C (PC) is a precursor of the serine protease, activated protein C (APC). Its proteolytic activation by thrombin occurs on the surface of endothelial cells and involves thrombomodulin and endothelial PC receptor (ERCP). Protein S (PS) also exerts an PCA-independent direct inhibitory effect on the prothrombinase complex by binding to FXa and FVa, and thus results in impaired prothrombin activation. In addition, PS stimulates the tissue factor pathway inhibitor. (TFPI) on FXa inactivation. Patients with hereditary deficiency of PC/PS are at high risk of recurrence of venous thromboembolism (VTE). A retrospective study in a large cohort of families has shown that the annual incidence of first recurrence after a first VTE episode was 6.0% (95% CI, 3.9–8.7) in patients with deficiency. of PC and 8.4% (95% CI, 5.8–11.7) in patients with PS deficiency. We present the case of a young male patient who developed an ischemic cerebrovascular event. The ranking prior to the event was 1 point. He had no relevant history. He denies intake of medications or cardiometabolic conditions. On physical examination, he presented a right crural monoparesis of 2/5. The simple skull tomography study showed an ischemic zone in the territory of the left anterior circuit. No arrhythmic alterations, structural cardiac lesion, no images were identified in the study of angiotomography of the skull. Thrombophilia tests were ordered, which identified a combined protein C and S deficiency. The risk of an arterial thrombotic event expressed as a cerebrovascular event is unknown since it is a truly atypical event. The present case is anecdotal given the infrequency of this type of event.La proteína C (PC) es un precursor de la serina proteasa, proteína C activada (PCA). Su activación proteolítica por trombina ocurre en la superficie del endotelio células e involucra trombomodulina y receptor de PC endotelial (RPCE). La proteína S (PS) también ejerce un efecto inhibidor directo independiente de PCA sobre el complejo de protrombinasa al unirse a FXa y FVa, y por tanto produce en la activación alterada de la protrombina. Además, la PS estimula el inhibidor de la vía del factor tisular. (IFT) en la inactivación de FXa. Los pacientes con deficiencia hereditaria de PC/PS tienen un alto riesgo de recurrencia de tromboembolismo venoso (TEV). Un estudio retrospectivo en una gran cohorte de familias ha demostrado que la incidencia anual de la primera recurrencia después de un primer episodio de TEV fueron del 6,0% (IC del 95%, 3,9–8,7) en pacientes con deficiencia de PC y del 8,4% (IC del 95%, 5,8–11,7) en pacientes con deficiencia de PS. Presentamos el caso de un paciente masculino joven quien desarrollo un evento cerebrovascular isquémico. El rankin previo al evento era de 1 punto. No presentaba antecedentes de importancia. Niega ingesta de medicaciones o condiciones cardiometabolicas. Al examen físico presento una monoparesia crural derecha de 2/5. El estudio de tomografía de cráneo simple mostro una zona isquémica en el territorio del circuito anterior izquierdo. No se identificaron alteraciones arrítmicas, lesión cardiaca estructural, no imágenes en el estudio de angiotomografia de cráneo. Se ordenaron pruebas de trombofilia las cuales identificaron déficit combinado de proteína C y S. El riesgo de un evento trombotico arterial expresado como evento cerebrovascular es desconocida ya que es un evento realmente atípico. El presente caso es anecdótico dada la escasa frecuencia de este tipo de eventos

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality