Study of Anticoagulant, Procoagulant, and Fibrinolytic Pathways in Mexican Patients With Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: In Mexico, the frequency of thromboembolic events associated to paroxysmal nocturnal hemoglobinuria is 3%; a clone size > 50% in granulocytes has been associated with a higher risk of thromboembolic events. METHODS: Between 2001 and 2012, 40 patients with paroxysmal nocturnal hemoglobinuria were studied. In 12 cases anticoagulant, procoagulant, and fibrinolytic pathways were analyzed. RESULTS: Only two of 40 patients (5%) developed a thromboembolic event over a 25.5-year follow-up period. From 12 patients, 91.7% had a paroxysmal nocturnal hemoglobinuria clone > 50% in granulocytes and 83.3% a clone > 50 % in monocytes. Five of 12 cases had elevated FV levels and four showed increased FVIII, von Willebrand factor antigen, von Willebrand factor ristocetin cofactor activity and FX. Protein S and protein C were decreased in nine and three patients, respectively. Only antithrombin correlated positively with paroxysmal nocturnal hemoglobinuria clone size in monocytes (p = 0.0442), whereas von Willebrand factor ristocetin cofactor correlated negatively with lactic dehydrogenase levels (p = 0.0186). No statistically significant associations were recorded with all other factors. CONCLUSION: The low frequency of thromboembolic events in Mexican patients could partly be explained by the associations between anticoagulant system (antithrombin) with paroxysmal nocturnal hemoglobinuria monocyte clone size, and procoagulant system (von Willebrand factor ristocetin cofactor) with lactic dehydrogenase levels.

Platelet activation and aggregation response to dengue virus nonstructural protein 1 and domains.

BACKGROUND: Platelets are now recognized as immunological sentries in the first line of defense that participate in the detection and response to pathogens. This frequently results in a decrease in the number of circulating platelets. Different mechanisms have been hypothesized to explain the thrombocytopenia in patients with severe dengue, one of them is the participation of the non-structural protein 1 (NS1) of dengue virus (DENV), which can be secreted into circulation during DENV infection and promotes a more efficient infection. OBJECTIVE: The present study aimed to investigate the ability of platelet response to stimulation with full-length DENV NS1 protein and its domains. METHODS: DENV NS1 plasmid was transfected into HEK-293T. Proteins were purified by Niquel Sepharose affinity chromatography. Secreted proteins were assessed by sodium dodecylsulfate polyacrylamide gel electrophoresis, Coomassie staining and western blot. Platelet-rich plasma was directly incubated with DENV NS1 proteins. Platelet activation was confirmed by expression of αIIbßIII and P-selectin by flow cytometry. Platelet aggregation was also assessed using DENV NS1 protein and its individual domains as agonists. RESULTS: DENV NS1 protein and its domains induce P-selectin and αIIbß3 complex expression on platelet surfaces. DENV NS1 induce a stable platelet aggregation after the addition of a minimal dose of adenosine diphosphate (ADP), epinephrine (EPI), or collagen. Interestingly, only EPI could induce the formation of platelet aggregates after incubation with the protein domains of NS1. CONCLUSION: Our results suggest that the full DENV NS1 protein and also its domains promote platelet recognition, activation, and aggregation.

Prevalence of iron, folate, and vitamin B12 deficiency anemia after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: One of the most common bariatric operations is the laparoscopic Roux-en-Y gastric bypass (LRYGBP) in which the gastric capacity is restricted and the absorption by the small intestine is reduced. The objective of this study was to evaluate the incidence of iron, folate, and vitamin B12 deficiency anemia in patients undergoing LRYGBP. PATIENTS AND METHODS: Clinical records of 30 patients who underwent LRYGBP between July 2003 and January 2005 and had a minimum follow up of 24 months at our outpatient clinic were included. Multivitamin supplementation was prescribed to all patients. The complete blood cell count, plasma iron, total iron-binding capacity, transferrin saturation, serum folate, and cobalamin levels before surgery, 6 months, 1, 2, and 3 years after the surgery were analyzed. RESULTS: There were 25 women (83.4%) and five men (16.6%) with ages from 21 to 56 years. Before surgery, two patients (6.6%) presented ferropenic anemia. Iron deficiency was seen in 40 and 54.5% 2 and 3 years after surgery, respectively. Cobalamin deficiency was observed in 33.3% at 2 years and in 27.2% at 3 years. At 2-year follow-up, 46.6% of the patients had already developed anemia and 63.6% at 3 years. Folate deficiency was not observed in any patient. CONCLUSION: Our routine scheme of vitamin supplementation is not sufficient to prevent iron and vitamin B12 deficiencies in most patients.

Consenso mexicano para el diagnóstico y tratamiento de la trombastenia de Glanzmann / Mexican consensus on the diagnosis and treatment of Glanzmann thrombasthenia

Resumen Las plaquetas tienen un papel central en diferentes escenarios fisiológicos, incluyendo la hemostasia; se unen unas con otras en la agregación plaquetaria, lo cual permite formar un coágulo plaquetario. Para que la agregación sea apropiada se requiere del complejo glicoproteico IIb/IIIa (GPIIb/IIIa) en la superficie plaquetaria. Toda alteración funcional plaquetaria, hereditaria o adquirida, impide la formación adecuada del coágulo y se manifiesta como hemorragia. Las enfermedades plaquetarias hereditarias son raras y, hasta recientemente, fueron ignoradas. Una de las más reconocidas y estudiadas es la trombastenia de Glanzmann (TG), entidad en la cual el número de plaquetas puede ser normal pero la función está alterada. Es un padecimiento autosómico y recesivo que causa hemorragia de diferente intensidad toda la vida y en la cual el problema radica en precisamente en la GPIIb/IIIa. Las hemorragias son típicamente mucocutáneas: equimosis, púrpura, epistaxis, gingivorragia; menos frecuentes son la hemorragia gastrointestinal, hemartrosis o en sistema nervioso central. La hiperpolimenorrea es común en las mujeres y llega a ser tan importante que amerita transfusiones en la menarca. La TG afecta a todos los grupos étnicos y su prevalencia varía entre 1/40,000 y 1/400,000. A pesar de esta información acerca de la TG en el mundo, hay pocas guías o recomendaciones basadas en la opinión de expertos y experiencias unicéntricas. En México la TG es rara y no se cuenta con una recomendación general para su diagnóstico y tratamiento. El objetivo de este documento fue establecer un consenso y hacer sugerencias generales para su diagnóstico y tratamiento.

Abstract Platelets have a central role in several physiological scenarios including hemostasis. Platelets bind each other during platelet aggregation allowing the proper formation of the clot; to be appropriate, platelet aggregation requires the glycoproteic complex IIb/IIIa (GPIIb/IIIa). Every platelet function abnormality both, congenital or acquired, impedes clot formation and favors bleeding episodes. Hereditary platelet abnormalities are rare and, until recently, they were almost ignored. Among these disorders, Glanzmann Thrombasthenia (GT) is a widely recognized abnormality in which platelet counts may be normal, but their function is affected. GT is an autosomal, recessive disease that causes life-long bleeding of different intensity. Main biochemical abnormality resides in GPIIb/IIIa. Bleeding is typically mucocutaneous: easy bruising, purpura, and nose and gum bleeds; less frequently are gastrointestinal bleeds, hemarthrosis, or intracranial. Menorrhagia and hyperpolymenorrhea are common findings in in women and may be the cause of anemia requiring blood transfusions at fertile age. GT affects all ethnic groups and its prevalence ranges between 1/40,000 to 1/400,000. Despite this worldwide information regarding GT, only a few guidelines and recommendations have been published, most of them based on expert opinions. In Mexico, GT is rare and there is not a general recommendation regarding its diagnosis and treatment. The aim of this document was to establish a consensus to suggest a general guideline for the diagnosis and treatment of GT in Mexico.

Coagulopatía, tratamiento anticoagulante en COVID-19 y trombosis posvacunación / Coagulopathy, anticoagulant treatment in COVID-19 and thrombosis postvaccine

Resumen La coagulopatía y la trombosis son situaciones graves que afectan a los pacientes con enfermedad por coronavirus 2019 (COVID-19) que requieren hospitalización. En estos pacientes se alteran mecanismos procoagulantes y fibrinolíticos que condicionan un estado procoagulante progresivo y grave. La anticoagulación oportuna en estos pacientes es importante, pero han surgido preguntas sobre el tipo, la dosis y el momento adecuado de la anticoagulación. Las directrices y documentos de consenso existentes ofrecen sugerencias generales sobre la dosis de heparinas de bajo peso molecular en función de la gravedad de la enfermedad y el riesgo de trombosis, pero todavía falta una relación entre los marcadores de coagulación y el régimen de anticoagulación. Se están llevando a cabo muchos ensayos clínicos que abordan estas cuestiones; se alienta la participación en estos ensayos para determinar las mejores estrategias de tratamiento para los pacientes de COVID-19. Es necesario aumentar los conocimientos con un rápido intercambio para atender adecuadamente a los pacientes en esta pandemia.

Abstract Coagulopathy and thrombosis are serious situations that COVID-19 patients require hospitalization. In these patients, procoagulant and fibrinolytic mechanisms are altered that condition a progressive and severe procoagulant state. Timely anticoagulation in these patients is important, but questions have been raised about the type, dose, and timing of anticoagulation. The guidelines and consensus documents offer general suggestions on the dose of LMWH based on the severity of the disease and the risk of thrombosis, but a relationship between coagulation markers and anticoagulation regimen is still lacking. Many clinical trials are underway that address these issues; Participation in these trials to determine the best treatment strategies for COVID-19 patients is encouraged. Increasing knowledge with rapid exchange is necessary to adequately care for patients in this pandemic.

Primary thrombophilia in Mexico: a single tertiary referral hospital experience.

Thrombophilia is a complex hypercoagulable state that increases the risk of thrombosis. Most reports in medical literature of the Mexican population with this disease lack statistical validity. Therefore, the aim of this study is to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. This is a study of patients referred to our hospital because of a hypercoagulable state and who later on were diagnosed with primary thrombophilia. The thrombophilia workup included methylenetetrahydrofolate reductase (MTHFR) C677T, antiphospholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, activated protein C resistance, JAK2 V617F and homocysteine. Ninety-five individuals were tested. The MTHFR C677T polymorphism was the most frequent anomaly in 84.1% of the tested individuals. There was a relatively low prevalence of factor V Leiden (5.2%) and anticoagulant protein deficiency (8.3%). The MTHFR C677T polymorphism has a very high prevalence compared with the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation in Mexicans.

Pulmonary hypertension secondary to hyperviscosity in a patient with rheumatoid arthritis and acquired von Willebrand disease: a case report.

INTRODUCTION: Acquired von Willebrand disease is initiated by autoantibodies and hyperviscosity syndrome caused by a massive polyclonal hypergammaglobulinemia. Acquired von Willebrand disease associated with autoimmune disease in addition to pulmonary hypertension during emergency room presentation is a rare condition. To the best of our knowledge, this is the second case reported in the literature treated with success; the first one was reported in 1987. CASE PRESENTATION: A 28-year-old mestizo man with a 3-year history of inflammatory arthritis was admitted to our hospital. An overlap of rheumatoid arthritis with systemic lupus erythematosus was suspected; therefore methotrexate was initiated, and later changed to leflunomide because of liver toxicity. Prothrombin time, international normalized ratio and activated partial thromboplastin times were normal (11/10.4 seconds; 1.2; 31.1/26.9 seconds, respectively), von Willebrand factor activity was observed with low ristocetin cofactor at 33.6UI/dL, high von Willebrand factor antigen >200UI/dL, and a low von Willebrand factor: ristocetin cofactor to von Willebrand factor antigen ratio. He was admitted to the emergency room with a 24-hour evolution of progressive dyspnea, cough, thoracic pain, and palpitations, 104 beats/min, 60/40 mmHg, temperature of 38°C, pulse oximetric saturation 88% and 30 breaths/minute. Cold, pale and mottled skin was also observed. He was then transferred to the intensive care unit. The placement of a pulmonary artery catheter was made. The initial patterns showed a precapillary pulmonary hypertension; acute pulmonary embolism was the first choice for diagnosis. Pulmonary angiography was conducted, and when no clot was discovered, pulmonary artery hypertension associated with connective tissue disease was considered. Serum protein electrophoresis confirmed the presence of a massive polyclonal hypergammaglobulinemia, and no paraproteinemia or monoclonal cell population was found from the electrophoretic pattern of the patient's plasma. Hypergammaglobulinemia was the cause of hyperviscosity syndrome associated with autoantibodies. Three sessions of plasma exchange therapy were made, and clinical improvement was observed. He was then discharged from the intensive care unit and hospital, respectively. He is now attended by an external consult and has no respiratory symptomatology. CONCLUSIONS: Hyperviscosity syndrome with pulmonary arterial hypertension presentation in a patient with acquired von Willebrand disease in an autoimmune context is a rare condition that can be treated successfully with plasmapheresis and critical care support.