Heparin Therapy Improving Hypoxia in COVID-19 Patients - A Case Series.

INTRODUCTION: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in São Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. RESULTS: PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(±90) to 325(±80), p = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events. DISCUSSION: Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.

Heparin therapy improving hypoxia in COVID-19 patients - a case series [preprint]

INTRODUCTION: Elevated D-dimer is predictor of severity and mortality in COVID-19 patients and heparin use during in hospital stay has been associated to decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting intravascular coagulation as a prominent feature of organ failure in these patients. Interestingly, in COVID19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to the Pulmonology service at Sirio-Libanes Hospital in São Paulo-Brazil treated with heparin in therapeutic doses tailored to clinical severity. RESULTS: PaO2/FiO2 ratio increased significantly over the 72 hours following the start of anticoagulation, from 254(±90) to 325(±80), p=0.013, and over half of the patients were discharged home within an average time of 7.3 (±4.0) days. Half of mechanically ventilated patients were extubated within 10.3 (±1.5) days. The remaining patients showed progressive improvement and there were no bleeding complications or fatal events. DISCUSSION: Even though this uncontrolled case series does not offer absolute proof of DIC as the underlying mechanism of respiratory failure in COVID-19, as well as patients positive response to tailored dose heparinization, it contributes to the understanding of the physiopathological mechanism of the disease and provides valuable information for the treatment of these very sick patients while we await the results of further prospective controlled studies

New anticoagulants for the treatment of venous thromboembolism.

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

New anticoagulants for the treatment of venous thromboembolism / Os novos anticoagulantes no tratamento do tromboembolismo venoso

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

O tromboembolismo venoso (TEV) está entre as principais causas de morte por doenças cardiovasculares no mundo, atrás apenas do infarto agudo do miocárdio e do acidente vascular cerebral. O TEV possui espectro de apresentação que vai desde a trombose venosa profunda até o tromboembolismo pulmonar agudo, de acordo com gravidade crescente de acometimento, sendo seu tratamento baseado na anticoagulação plena dos pacientes. Há muitas décadas, sabe-se que a anticoagulação interfere diretamente na mortalidade associada ao TEV. Até o início deste século a terapia anticoagulante se baseava no uso de heparina, em suas formas não fracionada ou de baixo peso molecular, e de antagonistas da vitamina K, principalmente a varfarina. Ao longo das últimas décadas, foram desenvolvidos novas classes de medicamentos anticoagulantes, inibidores do fator Xa e inibidores diretos da trombina, que mudaram significativamente o arsenal terapêutico do TEV, em função de suas características de eficácia e segurança em relação ao tratamento convencional, sendo o foco principal de esta revisão avaliar seu papel neste contexto clínico.

Skeletal muscle abnormalities in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH. METHODS: The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls. RESULTS: PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO2 max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output. CONCLUSION: Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH.

Schistosomiasis and pulmonary hypertension.

Schistosomiasis is one of the most prevalent chronic infectious diseases in the world. One of its most severe complications, pulmonary hypertension, occurs in up to 5% of patients with hepatosplenic schistosomiasis. The prevalence of schistosomiasis is so overwhelming that schistosomiasis-associated pulmonary hypertension (Sch-PH) may be the most prevalent cause of pulmonary hypertension around the world. Multiple pathways have been described as potential mechanisms of disease in Sch-PH, such as egg embolism, inflammatory disease or pulmonary blood overflow. The possible physiopathological mechanisms will be discussed in this article, as well the disease's clinical course and response to the treatment available.