COVID-19 Infection and Myocardial Infarction Pathophysiology and Therapy

The relationship between COVID-19 and cardiovascular disease has been of interest since the beginning of the pandemic, with the focus more recently shifting towards thrombotic complications, including myocardial infarction (MI). While the inflammatory burden of infection has previously been implicated in the pathogenesis of MI, at least early in the pandemic, many hospitals were seeing fewer ST-elevation MI admissions and the delivery of acute coronary syndrome care was disrupted in multiple ways. Furthermore, patients presenting with both COVID-19 infection and MI have been noted in small studies to have unique characteristics that pose clinical challenges, and there is reason to believe that standard therapy for both the prevention and treatment of all thrombotic events, including MI, may not be adequate. The aim of this article is to review the data regarding MI and other thrombotic events during the pandemic, to explore the link between inflammation and thrombosis, and to suggest possible novel therapeutic options for the treatment and prevention of thrombosis in patients with COVID-19.

Protective Role of Platelets in Myocardial Infarction and Ischemia/Reperfusion Injury

Thrombotic occlusion of the coronary artery is a key component in the pathogenesis of myocardial ischemia and myocardial infarction (MI). The standard therapy for ischemia is revascularization and restoration of blood flow to previously ischemic myocardium. Paradoxically, reperfusion may result in further tissue damage called ischemia/reperfusion injury (IRI). Platelets play a major role in the pathogenesis of MI and IRI, since they contribute to the thrombus and microthrombi formation, inflammation, release of immunomodulatory mediators, and vasoconstrictive molecules. Antiplatelet therapies have proven efficacy in the prevention of thrombosis and play a protective role in cardiac IRI. Beyond the deterioration effect of platelets in MI and IRI, in the 90s the first reports on a protective effect of molecules released from platelets during MI appeared. However, the role of platelets in cardioprotection is still poorly understood. This review describes the involvement of platelets in MI, IRI, and inflammation. It mainly focuses on the protective role of platelets in MI and IRI. Platelets are involved in cardioprotection based on platelet-releasing molecules and antiplatelet therapy, apart from antiaggregatory effects. Additionally, the use of platelet-derived microparticles as possible markers of MI, with and without comorbidities, and their role in cardioprotection are discussed. This review is aimed at illustrating the present knowledge on the role of platelets in MI and IRI, especially in a context of cardioprotection.

Antithrombotic Effects of Montelukast by Targeting Coagulation Factor XIa

Current oral anticoagulants prescribed for the prevention of thrombosis suffer from severe hemorrhagic problems. Coagulation factor XIa (FXIa) has been confirmed as a safer antithrombotic target as intervention with FXIa causes lower hemorrhagic risks. In this study, by a high-throughput virtual screening, we identified Montelukast (MK), an oral antiasthmatic drug, as a potent and specific FXIa inhibitor (IC50 = 0.17 µM). Compared with the two mostly prescribed anticoagulants (Warfarin and Apixaban), MK demonstrated comparable or even higher antithrombotic effects in three independent animal models. More importantly, in contrast to the severe hemorrhage caused by Warfarin or Apixaban, MK did not measurably increase blood loss in vivo. In addition, MK did not affect the hemostatic function in plasma from healthy individuals. In contrast, MK suppressed clot formation in clinical hypercoagulable plasma samples. This study provides a lead compound of anticoagulants targeting FXIa, and suggests the exploratory clinical researches on antithrombotic therapies using MK.

Secondary prevention of thrombosis with direct oral anticoagulants for hereditary hematogenous thrombophilia

Aim. The article describes the experience of using direct oral anticoagulants – drugs Dabigatran, Rivaroxaban and Apixaban for the secondary prevention of thrombosis in patients with the most common variants of hereditary hematogenous thrombophilia.Materials and methods. 86 patients were under observation: 53 men, 33 women. Only the registered fact of thrombosis, thromboembolism, ischemia or organ infarction was the basis for the diagnosis of hematogenous thrombophilia and further secondary prevention of thrombosis. In 80 cases, there was a combined form of thrombophilia. In addition to hereditary factors, there were acquired thrombogenic factors. Dabigatran etexilate (Pradaxa®) for the prevention of thrombus formation was prescribed to 41 patients aged 20 to 60 years; duration of admission from 12 months to 9 years, the dose of the drug was selected individually from 150 to 300 mg per day. Rivaroxaban (Xarelto®) for the prevention of thrombus formation was prescribed to 25 patients aged 18 to 54 years, duration of admission from 12 months to 7 years, the dose of the drug is 10-20 mg per day. Apixaban (Eliquis®) was prescribed to 10 patients, aged 30 to 50 years, the duration of admission was from 6 months up to 2 years, dosage 5-10 mg per day. For hyperhomocysteinemia, Angiovit® or Pentavit® was prescribed. Protein C and antithrombin III preparations with their congenital deficiency were used according to indications.Results. After Dabigatran was prescribed, only one patient had a recurrent pulmonary embolism due to low adherence to treatment. In other patients who were prescribed direct oral anticoagulants, no recurrence of thrombotic complications was recorded. No hemorrhagic complications were diagnosed with the use of Dabigatran and Apixaban. In 5 patients receiving Rivaroxaban, there were minor epistaxis; in three cases they stopped when the dose was reduced from 20 to 15-10 mg, two patients were transferred to dabigatran. No life-threatening bleeding has been reported.Conclusion. Dabigatran, Rivaroxaban and Apixaban are effective and safe drugs for antithrombotic therapy. The absence of the need for constant laboratory monitoring and extremely rare hemorrhagic complications makes it possible to use them in patients living in areas remote from large medical centers. Only 10 patients under our supervision with a diagnosis of “hematogenous thrombophilia” are currently taking warfarin. Timely diagnosis of the variant of hematogenous thrombophilia and the appointment of adequate anti-thrombotic therapy contributes to the relapse-free course of the disease.

Oral Squamous Cell Carcinoma Is Associated with a Low Thrombosis Risk Due to Storage Pool Deficiency in Platelets

Venous thrombo-embolism (VTE) disease is the second most common cause of mortality in cancer patients, and evaluation and prevention of thrombosis risk is essential. VTE-associated risk varies according to the type of tumor disease. Oral cancer is the most frequent type of head and neck cancer, and it represents approximately 2.1% of all cancers worldwide. Most tumors are squamous cell carcinomas and are mainly due to tobacco and alcohol abuse. VTE risk associated with oral squamous cell carcinoma (OSCC) is low. However, many studies have shown that OSCC has the following biological features of cancers associated with a high thrombosis risk: modified thrombosis and fibrinolysis mechanisms; strong expression of procoagulant proteins; secretion of procoagulant microparticles; and production of procoagulant cytokines. Using an original mouse model of tongue squamous cell carcinoma, our study aimed to clarify this paradoxical situation. First, we showed that OSCC tumors have a pro-aggregatory phenotype and a high local thrombosis risk. Second, we found that tongue tumor mice do not have an elevated systemic thrombosis risk (the risk of an “at distance” thrombosis event such as lower extremity deep venous thrombosis or pulmonary embolism) and even show a reduction in risk. Third, we demonstrated that tongue tumor mice show a reduction in platelet reactivity, which explains the low systemic thrombosis risk. Finally, we found that tongue tumor mice present granule pool deficiency, thereby explaining the reduction in platelet reactivity and systemic thrombosis risk.

Possibility to use direct oral anticoagulants to prevent thromboembolic events in patients with COVID-19

Hospitalized patients with COVID-19 who have not previously received DOAK by it is not advisable to prescribe POAC for the prevention of thrombosis in patients with COVID-19 due to the lack of clinical trial results, significant potential interactions.

Thrombotic coagulopathy and COVID-19

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). COVID-19 has been an exceptional challenge for the health system thoughout the world. Many publications have emerged in a very short time and have had to be interpreted quickly to try to clarify the doubts generated by the new disease. Evidence of abnormal coagulation parameters associated with COVID-19 appeared in early reports from China. Venous thromboembolism (VTE) and microvasculature thrombosis have been found in many of hospitalized patients, specially in more severe cases. Severe inflammation is presents in patients with SARS-CoV2 infection. The coagulation activation has been associated to reaction of host defense systems, such as immflamatory response and innate immunity pathways, a term called immunothrombosis or thromboinflammation. COVID-19-associated coagulopathy reflects unusual abnormalities present in hypercoagulable states that accompany other infections. Here, we review clinical data and mechanisms of coagulation abnormalities that occur in association with COVID-19. Moreover we show several Guides to provide practical information for the prophylaxis and management of VTE in hospitalized patients with COVID-19. The knowledge of this new pathogen, of its pathogenicity and treatment are evolving rapidly, and our understanding and approach for the therapy and prevention of thrombosis will continue to evolve.

Causes and Management of Non-cirrhotic Portal Hypertension​

Purpose of the Review Non-cirrhotic portal hypertension (NCPH) includes a heterogeneous group of conditions. The aim of this paper is to make an overview on the denominations, diagnostical features and management of porto-sinusoidal vascular disease (PSVD) and chronic portal vein thrombosis (PVT) being the main causes of NCPH in the Western world. Recent Findings The management of NCPH consists in the treatment of associated diseases and of portal hypertension (PH). PH due to PSVD or PVT is managed similarly to PH due to cirrhosis. TIPS placement and liver transplantation are considerable options in patients with refractory variceal bleeding/ascites and with progressive liver failure. Anticoagulation is a cornerstone both in the treatment of thrombosis in PSVD and in the prevention of thrombosis recurrence in patients with portal cavernoma. Summary Physicians should be aware of the existence of PSVD and chronic PVT and actively search them in particular settings. To now, the management of portal hypertension-related complications in NCPH is the same of those of cirrhosis. Large cooperative studies on the natural history of NCPH are necessary to better define its management.