COVID-19 coagulopathy - what should we treat?

NEW FINDINGS: What is the topic of this review? Overview of the coagulation abnormalities, including elevated D-dimers widely reported with COVID-19, often labelled as COVID coagulopathy. What advances does it highlight? The review highlights the changes in bronchoalveolar haemostasis due to apoptosis of alveolar cells, which contributes to acute lung injury and acute respiratory distress syndrome; the pathophysiological mechanisms, including endothelial dysfunction and damage responsible for thrombosis of pulmonary microcirculation and potential contribution to the hypoxaemia of COVID-19 acute lung injury; and changes in coagulation proteins responsible for the hypercoagulability and increased risk of thrombosis in other venous and arterial beds. The rationale for anticoagulation and fibrinolytic therapies is detailed, and potential confounders that might have led to less than expected improvement in the various randomised controlled trials are considered. ABSTRACT: Coronavirus disease 19 (COVID-19) causes acute lung injury with diffuse alveolar damage, alveolar-capillary barrier disruption, thrombin generation and alveolar fibrin deposition. Clinically, hypoxaemia is associated with preserved lung compliance early in the disease, suggesting the lack of excessive fluid accumulation typical of other lung injuries. Notably, autopsy studies demonstrate infection of the endothelium with extensive capillary thrombosis distinct from the embolic thrombi in pulmonary arteries. The inflammatory thrombosis in pulmonary vasculature secondary to endothelial infection and dysfunction appears to contribute to hypoxaemia. This is associated with elevated D-dimers and acquired hypercoagulability with an increased risk of deep vein thrombosis. Hypercoagulability is secondary to elevated plasma tissue factor levels, von Willebrand factor, fibrinogen, reduced ADAMTS-13 with platelet activation and inhibition of fibrinolysis. Multi-platform randomised controlled studies of systemic therapeutic anticoagulation with unfractionated and low molecular mass heparins demonstrated a survival benefit over standard care with full-dose anticoagulation in patients with non-severe disease who require supplemental oxygen, but not in severe disease requiring ventilatory support. Late intervention and the heterogeneous nature of enrolled patients can potentially explain the apparent lack of benefit in severe disease. Improvement in oxygenation has been demonstrated with intravenous fibrinolytics in small studies. Inhaled anticoagulants, thrombolytic agents and non-specific proteolytic drugs in clinical trials for decreasing alveolar fibrin deposition might benefit early disease. Essentially, COVID-19 is a multi-system disorder with pulmonary vascular inflammatory thrombosis that requires an interdisciplinary approach to combination therapies addressing both inflammation and intravascular thrombosis or alveolar fibrin deposits to improve outcomes.

Fibrinolytic Administration via EkoSonic™ Endovascular System (EKOS) Catheter Used in Acute Aortic Occlusion Secondary to COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 is the virus responsible for the 2019 global pandemic. Pulmonary complications of COVID-19 are well established in the literature. However, the virus causes numerous extrapulmonary manifestations, notably acute aortic occlusion (AAO). COVID-19 creates a hypercoagulable state via the upregulation of numerous procoagulant cytokines in endothelial cells of blood vessels. We present a case of a 63-year-old patient without a previous history of prothrombotic disorders who developed AAO in the distal abdominal aorta and bilateral common iliac arteries after contracting COVID-19. The patient was a poor surgical candidate and was treated with fibrinolytics that were administered via an EkoSonic™ Endovascular System (EKOS) catheter using a bilateral transfemoral approach. This case highlights a unique treatment option for non-surgical candidates with AAO.

The Potency of Seaweed Sulfated Polysaccharides for the Correction of Hemostasis Disorders in COVID-19.

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.

Treatment of ST-Segment Elevation Myocardial Infarction During COVID-19 Pandemic.

The number of cases of the coronavirus-induced disease-2019 (COVID-19) continues to increase exponentially worldwide. In this crisis situation, the management of ST-segment elevation myocardial infarction (STEMI) is challenging. In this review, we outline the risks and benefits of primary PCI vs. thrombolysis for STEMI. While thrombolysis may seem like a good choice, many patients have a contraindication and could end up using more resources. Also, with a high probability of the angiogram showing non-obstructed coronary arteries during acute infections, primary PCI should be the preferred strategy.