COVID-19 vaccines and thrombosis with thrombocytopenia syndrome

Authors: Chih-Cheng Lai 1Wen-Chien Ko 2Chih-Jung Chen 3Po-Yen Chen 4Yhu-Chering Huang 3Ping-Ing Lee 5Po-Ren Hsueh 6 7

Abstract

Introduction: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination.

Areas covered: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS.

Expert opinion: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity.

Plain language summary: What is the context? Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines. TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality. What is new? TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated. What is the impact? TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.

For More Information: https://pubmed.ncbi.nlm.nih.gov/34176415/

Anticoagulation in COVID-19: current concepts and controversies

  1. Authors: http://orcid.org/0000-0002-3809-8926Atanu Chandra16289Uddalak Chakraborty2, Shrestha Ghosh1, Sugata Dasgupta3

Abstract

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

Introduction

The novel beta-coronavirus, appropriately named SARS-CoV-2 by the International Committee of Taxonomy of Viruses, belongs to a family of single-stranded RNA viruses, members of which have been recognised as causative agents of the SARS-CoV and Middle East respiratory syndrome coronavirus outbreak in 2002 and 2012, respectively.1 2 Presently, the novel COVID-19 poses a major global health crisis, having been declared a pandemic on 11 March 2020 by the WHO.

Over the past several months, an overwhelming amount of literature suggests an increased risk of thromboembolic manifestations associated with COVID-19.2 Several hypotheses have been suggested to understand the underlying pathophysiology behind development of a prothrombotic state in COVID-19 such as exaggerated inflammatory response resulting in activation of the coagulation cascade and endothelial injury.3 4 Usage of anticoagulants in COVID-19 remains an area of conjecture with no definite guidelines published to date highlighting the timing, dosage and duration of anticoagulation as well as the drug of choice. Most internationally published guidelines, based on consensus statements and expert opinions, recommend therapeutic doses of heparin only in patients diagnosed with or highly suspected of developing macrothrombi such as pulmonary embolism (PE) or deep vein thrombosis (DVT). However, these guidelines including those by CHEST, rarely address the requirement of post discharge thromboprophylaxis.5

For More Information: https://pmj.bmj.com/content/early/2021/04/12/postgradmedj-2021-139923

Better Anticoagulated Than Not! Hypercoagulability in COVID-19

Authors: Dhauna P. Karam, MD1

Incidence of thrombotic complications in patients with COVID-19 who are critically ill is high, with an estimated incidence of 31% for arterial or venous thromboembolism (VTE), acute pulmonary embolism, ischemic stroke, and myocardial infarction. On the basis of the study by Klok et al,1 pulmonary embolism was the most common thrombotic complication in critically ill patients with COVID-19 despite being on standard anticoagulation. Prevention of thromboembolism with anticoagulants is recommended in all critically ill patients with COVID-19.

The American Society of Hematology (ASH) guideline panel (updated April 7, 2021) recommends prophylactic anticoagulation in all critically ill patients with COVID-19 without suspected or confirmed venous thromboembolism (VTE). ASH defines patients with COVID-19 critical illness as someone who is suffering from a life-threatening condition, typically admitted in an intensive care unit. It is recommended that individualized assessment of the patient’s thrombotic and bleeding risk needs to be performed before deciding on anticoagulation.2 What about hospitalized patients with COVID-19 who are not critically ill? What are some clinical parameters that can be used to guide decisions on anticoagulant use in such patients?

The accompanying manuscript by Gaddh et al3 reports guidelines used in a large academic institution, Emory University School of Medicine, Atlanta, Georgia, to determine anticoagulation in hospitalized patients with COVID-19. The guidelines were created by a multidisciplinary panel of experts and were incorporated into frontline care at Emory. The three-tiered algorithm was used to risk stratify patients admitted with a primary diagnosis of COVID-19. It was not recommended for use in patients incidentally found to have COVID-19 during hospitalization for other causes. On the basis of the guidelines, patients with normal D-dimer, no evidence of thromboembolism and not critically ill were given prophylactic anticoagulation (group 1). Patients with elevated D-dimer (> 6 times upper limit normal) with no evidence of thromboembolism and not critically ill were given intermediate-dose anticoagulation. Patients critically ill without any evidence of thromboembolism and without elevation of D-dimer were also given intermediate-dose anticoagulation. Patients with confirmed thromboembolism or those with other markers of possible thromboembolism (worsening hypoxia or pulmonary status without identifiable cause and limb edema) received therapeutic anticoagulation. Anticoagulation was continued for 1 week after discharge in group 1 patients. Group 2 received anticoagulation for 4-6 weeks after discharge. Finally, group 3 received anticoagulation for minimum 3 months postdischarge. Preliminary findings revealed low bleeding complications. Data on type of anticoagulant used, incidence of thromboembolism in the hospitalized group following the above guidelines, and improvement in morbidity and mortality rates were not provided. The algorithm is a simple, practical statement, which can guide frontline caregivers until evidence-based recommendations become available. Group 1 and 3 recommendations are supported by major organizational guidelines such as ASH and International Society on Thrombosis and Haemostasis (ISTH). Preliminary guidelines from these organizations refrain from commenting strongly on intermediate-dose anticoagulation in the absence of supporting data from clinical trials but do support anticoagulant dose escalation on the basis of clinician’s assessment for high-risk patients.2,4

For More Information: https://ascopubs.org/doi/full/10.1200/OP.21.00359