Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group.

Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.

Real-world data with the use of caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura: A single-center with homogeneous treatment experience.

BACKGROUND: Recently, real-world data confirmed the effectiveness of caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP); however, limitations as different treatment protocols from multicenter experiences and the front-line use of rituximab could overshadow the real impact of the addition of caplacizumab. STUDY DESIGN AND METHODS: We report the clinical characteristics and response to treatment of 30 consecutive cases of aTTP treated under a homogeneous therapeutic protocol with the only exception of the addition of caplacizumab in the last 10 cases (caplacizumab group), whose primary outcome we compare with the previous 20 cases (control group). RESULTS: Caplacizumab was started at a median of 2.5 days after diagnosis (interquartile range [IQR] 1-4) and maintained for a median of 37.5 days (IQR 32-39). Safety was in line with previous reports with 30% of patients showing mild adverse events, the most common bleeding. The caplacizumab group achieved platelet count normalization after a median of 3 (IQR 2-5) versus 4 (IQR 2-8.5) days in the control group (p = .067). The caplacizumab group required a lower median number of plasma exchanges, 10 (IQR 9-11) versus 16.5 (IQR 11-20) in the control group (p = .0053) and a shorter length of hospitalization, 12 (IQR 12-14) vs. 22 (IQR 15-27) days (p = .0025). There were no refractory cases and no deaths in the caplacizumab group compared to five refractory cases and three aTTP-related death (15%) in the control group. DISCUSSION: Our experience confirms improvement in the outcomes with a decrease in refractoriness and mortality since the introduction of caplacizumab.

Plasmapheresis for the Treatment of Acute Pancreatitis due to Severe Hypertriglyceridemia.

Severe hypertriglyceridemia (HTG) is associated with acute pancreatitis (AP). Treatment options include total plasma exchange (TPE). We report a case of AP due to severe HTG treated with TPE.

Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos / Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants

Antecedentes y objetivos: En los últimos años los anticoagulantes orales directos (ACOD) se han convertido en una alternativa a los antagonistas de la vitamina K (AVK) para la prevención del ictus y embolia sistémica en pacientes con fibrilación auricular no valvular (FANV), así como para la prevención y tratamiento de la trombosis venosa profunda. Los ensayos clínicos han demostrado la no inferioridad y la potencial superioridad en comparación con la warfarina, lo cual permite ampliar las opciones de anticoagulación. En nuestro medio, las Unidades de Tratamiento Anticoagulante (UTA) y los Centros de Atención Primaria (CAP) son los encargados de la educación, seguimiento, control de adherencia y del manejo en situaciones especiales de los pacientes anticoagulados. Estas consideraciones han motivado la preparación del presente documento de consenso, que tiene como objetivo establecer recomendaciones que incorporen los hallazgos de la investigación científica a la práctica clínica para mejorar la calidad asistencial en el ámbito de la anticoagulación. Material y métodos: Un grupo de expertos del Grupo Catalán de Trombosis (TROMBOC@T) ha revisado la bibliografía publicada entre 2007 y 2016 para poder establecer recomendaciones basadas en la evidencia clínica. Resultados: Como resultado del proyecto se han establecido un conjunto de recomendaciones de carácter práctico que facilitarán el tratamiento, educación, seguimiento y manejo en situaciones especiales de los pacientes anticoagulados con ACOD. Conclusiones: El aumento progresivo del uso de los ACOD requiere establecer y homogeneizar las directrices de actuación clínica en el paciente anticoagulado con estos antitrombóticos tanto en las UTA como en los CAP

Background and objectives: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. Material and methods: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. Results: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. Conclusions: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs

Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants. / Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos.

BACKGROUND AND OBJECTIVES: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. MATERIAL AND METHODS: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. RESULTS: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. CONCLUSIONS: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Impact of Implementing a Protocol on the Perioperative Management in Patients Treated with Antithrombotics Admitted for Hip Fracture Surgery: an Observational Study.

This study aimed to describe the impact of implementing a protocol on the perioperative management of patients admitted for hip fracture treated with antithrombotics. A protocol was designed based on the recommendations from the American College of Chest Physicians (ACCP). After its implementation (May 2012), information on antithrombotic management was collected from admission to 3 months after surgery in retrospective (October 2011-March 2012) and prospective (October 2012-March 2013) cohorts. Patients' thromboembolic risk was classified into high, moderate or low according to the ACCP categories. A total of 113 and 101 cases were included in the retrospective and prospective cohorts, respectively. No differences in age, gender, American Society of Anaesthesiology score or thrombotic risk categories were observed between cohorts. Most patients were treated with aspirin or triflusal (55.1% and 48.1% in each cohort, respectively), clopidogrel (24.5% and 26.6%) or acenocoumarol (16.3% and 20.2%). In moderate to high thromboembolic risk patients, a higher rate of bridging therapy with full doses of enoxaparin (18.5% and 50%, p = 0.04 before and 9.1% and 43.7%, p = 0.02 after surgery) and a lower rate of aspirin discontinuation (76% and 55.3%, p = 0.03) were observed in the prospective cohort. Both cohorts had a similar percentage of cases with bleeding (68.1% and 68.3%) and thrombotic events (11.5% and 13%). No differences in the timing between surgery and the discontinuation or resumption of antithrombotics were noted. After the protocol implementation, aspirin was less often stopped and bridging therapy with therapeutic doses of enoxaparin was used more often. However, interruption and resumption times of antithrombotics remained almost unchanged. In order to achieve these goals, more efforts should be made to implement the protocol in clinical practice.

Beyond hemostasis: the challenge of treating plasminogen deficiency. A report of three cases.

Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.

A spectrum of severe familial liver disorders associate with telomerase mutations.

BACKGROUND: Telomerase is an enzyme specialized in maintaining telomere lengths in highly proliferative cells. Loss-of-function mutations cause critical telomere shortening and are associated with the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia and with idiopathic pulmonary fibrosis. Here, we sought to determine the spectrum of clinical manifestations associated with telomerase loss-of-function mutations. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-nine individuals from five unrelated families with a variety of hematologic, hepatic, and autoimmune disorders were screened for telomerase complex gene mutations; leukocyte telomere length was measured by flow fluorescence in situ hybridization in mutation carriers and some non-carriers; the effects of the identified mutations on telomerase activity were determined; and genetic and clinical data were correlated. In six generations of a large family, a loss-of-function mutation in the telomerase enzyme gene TERT associated with severe telomere shortening and a range of hematologic manifestations, from macrocytosis to acute myeloid leukemia, with severe liver diseases marked by fibrosis and inflammation, and one case of idiopathic pulmonary fibrosis but not with autoimmune disorders. Additionally, we identified four unrelated families in which loss-of-function TERC or TERT gene mutations tracked with marrow failure, pulmonary fibrosis, and a spectrum of liver disorders. CONCLUSIONS/SIGNIFICANCE: These results indicate that heterozygous telomerase loss-of-function mutations associate with but are not determinant of a large spectrum of hematologic and liver abnormalities, with the latter sometimes occurring in the absence of marrow failure. Our findings, along with the link between pulmonary fibrosis and telomerase mutations, also suggest a common pathogenic mechanism for fibrotic diseases in which defective telomere repair plays important role.