Comprehensive evaluation of genetic and acquired thrombophilia markers for an individualized prediction of clinical thrombosis in patients with lymphoma and multiple myeloma.

Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting.

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.

Incidence and clinical profile of venous thromboembolism in hospitalized COVID-19 patients from Madrid region.

BACKGROUND: COVID-19 related in-hospital venous thromboembolism (VTE) incidence is high but data reported vary significantly. Some studies show that up to half of the events are diagnosed early after admission. OBJECTIVES: To study symptomatic VTE incidence in acute COVID-19 hospitalized patients and to describe timing of VTE diagnosis. METHODS: Multicenter cohort of 5966 patients hospitalized with acute COVID-19. Multicenter Registry of 844 hospitalized patients with acute COVID-19 and associated acute VTE. RESULTS: By the time of cohort data collection, 68 patients (1.14%) were still hospitalized, 19.8% had died, and 5.4% required ICU. During a median follow-up of 6 days (IQR, 4-12), 183 patients (3.07%; 95% CI, 2.64-3.55) presented a symptomatic VTE event. The cumulative incidences of VTE at 7, 14 and 21 days in wards [2.3% (95% CI, 1.9-2.7), 3.6% (95% CI, 3.0-4.3), and 4.3% (95% CI, 3.5-5.1)] were similar to the ones reported in ICU [2.2% (95% CI, 1.0-4.4), 2.9% (95% CI, 1.5-5.3), and 4.1% (95% CI, 2.2-6.8)], but at 30 and 60 days were higher in ICU [6.9% (95% CI, 4.2-10.5), and 12.8% (95% CI, 8.1-18.5)] than in wards. Eighty-eight VTE events (48%) were diagnosed early, within 48 h of admission. VTE was not associated with death (HR, 0.79; 95% CI, 0.55-1.12). CONCLUSIONS: Incidence of symptomatic VTE in our COVID-19 cohort is consistent with that of other real-life studies recently published. Early VTE events are, along with COVID-19, the reason for admission rather than an in-hospital complication.

Autoimmune haemolytic anaemias: A retrospective study of 93 patients. / Anemias hemolíticas autoinmunes: estudio retrospectivo de 93 pacientes.

INTRODUCTION: Autoimmune haemolytic anaemia (AIHA) is an infrequent and heterogeneous disease in its pathophysiology and clinical behaviour, therefore it is generally managed empirically. PATIENTS AND METHODS: We conducted an observational, retrospective and multicentre study of 93 patients diagnosed with AHAI in 9 Spanish hospitals between 1987 and 2017, with a median follow-up of 28 months. RESULTS: Median age of 67 years; 85% AHAI for hot antibodies and 64% primary AHAI. The lowest haemoglobin values at diagnosis related to patients under 45 years of age and serological type IgG+C. Of the patients, 92% received first line treatment, 54% second line, and 27% third line. The warm AHAI were treated in first line with steroids, with overall responses of 83% and complete of 58%. Rituximab in monotherapy or in association with steroids was administered to 34 patients with overall responses close to 100% (complete responses 40-60%), relegating splenectomy to the third line. The immunosuppressive treatment was administered in patients with autoimmune diseases or in corticoid-dependent patients. DISCUSSION: We found high rates of response to steroids, with very prolonged treatments that cause side effects and corticoid dependence in a third of patients. The combination of steroids with rituximab in the first line, could be indicated in patients with low levels of haemoglobin and serological type IgG+C. The high relapse rates make necessary the development of randomised studies with new drugs or the combination with existing ones, which allow longer response times and with fewer side effects.

Anemias hemolíticas autoinmunes: estudio retrospectivo de 93 pacientes / Autoimmune haemolytic anaemias: A retrospective study of 93 patients

INTRODUCCIÓN: Las anemias hemolíticas autoinmunes (AHAI) son enfermedades poco frecuentes y heterogéneas en su fisiopatología y comportamiento clínico, siendo el manejo de las mismas fundamentalmente empírico. PACIENTES Y MÉTODOS: Realizamos un estudio observacional, retrospectivo y multicéntrico de 93 pacientes diagnosticados de AHAI en 9 hospitales españoles entre 1987 y 2017, con una mediana de seguimiento de 28 meses. RESULTADOS: Mediana de edad de 67 años; un 85% de AHAI por anticuerpos calientes y un 64% AHAI primarias. Los valores de hemoglobina más bajos al diagnóstico se relacionaron con edad<45 años y el tipo serológico IgG+C. Un 92% recibieron tratamiento de primera línea, un 54% de segunda línea y un 27% de tercera línea. Las AHAI calientes fueron tratadas en primera línea con esteroides, con respuestas globales del 83% y completas del 58%. El rituximab en monoterapia o asociado a esteroides se administró a 34 pacientes con respuestas globales cercanas al 100% (respuestas completas 40-60%), relegando la esplenectomía a tercera línea. El tratamiento inmunosupresor se administró en pacientes con enfermedades autoinmunes o en dependientes de corticoides. DISCUSIÓN: Encontramos altas tasas de respuesta a esteroides, con tratamientos muy prolongados que provocan efectos secundarios y corticodependencia en un tercio de los pacientes. La asociación de esteroides con rituximab en primera línea podría estar indicada en pacientes con bajos niveles de hemoglobina y tipo serológico IgG+C. Las altas tasas de recaída hacen necesario el desarrollo de estudios aleatorizados con nuevos fármacos o la asociación con los ya existentes, que permitan mayor duración de las respuestas y con menores efectos secundarios

INTRODUCTION: Autoimmune haemolytic anaemia (AIHA) is an infrequent and heterogeneous disease in its pathophysiology and clinical behaviour, therefore it is generally managed empirically. PATIENTS AND METHODS: We conducted an observational, retrospective and multicentre study of 93 patients diagnosed with AHAI in 9 Spanish hospitals between 1987 and 2017, with a median follow-up of 28 months. RESULTS: Median age of 67 years; 85% AHAI for hot antibodies and 64% primary AHAI. The lowest haemoglobin values at diagnosis related to patients under 45 years of age and serological type IgG+C. Of the patients, 92% received first line treatment, 54% second line, and 27% third line. The warm AHAI were treated in first line with steroids, with overall responses of 83% and complete of 58%. Rituximab in monotherapy or in association with steroids was administered to 34 patients with overall responses close to 100% (complete responses 40-60%), relegating splenectomy to the third line. The immunosuppressive treatment was administered in patients with autoimmune diseases or in corticoid-dependent patients. DISCUSSION: We found high rates of response to steroids, with very prolonged treatments that cause side effects and corticoid dependence in a third of patients. The combination of steroids with rituximab in the first line, could be indicated in patients with low levels of haemoglobin and serological type IgG+C. The high relapse rates make necessary the development of randomised studies with new drugs or the combination with existing ones, which allow longer response times and with fewer side effects