July 2023 Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1

This study investigated the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines. The researchers analysed 12.3 million (16+ years old) individuals between December 2020 and June 2022; 6,306,306 with BNT162b2 and 6,046,785 were vaccinated with ChAdOx1.

Results found no increased risk of venous thromboembolic events (VTE) and cerebral venous sinus thrombosis (CVST) for both vaccines. Additionally, there was no elevated risks for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events.

November 2022 Acute and postacute sequelae associated with SARS-CoV-2 reinfection.

This article investigated whether there is increased risk with reinfection of the SARS-CoV-2 virus. The cohort consisted of people infected once (443,588), infected 2+ times (40,947) and a control comprising of 5,334,729 individuals who have not been infected.

The risks were mostly prominent in the acute phase but persevered into the post-acute phases - 6 months later at 30-day increments. Those with reinfection of the SARS-CoV-2 virus demonstrated increased risk and excess burden of all-mortality, hospitalisation and at least one sequelae (pulmonary, cardiovascular, coagulation and haematological disorders, diabetes, gastrointestinal and neurological), in the acute and was still evident 180 days after reinfection.

All-cause mortality and excess burden of all-cause mortality was estimated at 19.33 per 1,000 persons at 6-months, compared to those with no reinfection. The risks were apparent regardless of vaccination status. Compared to those who have not been infected, cumulative risks and burdens of repeat infection increased according to the number of infections. This study demonstrates that prevention of reinfection of the SARS-CoV-2 virus may protect from additional health risks.

September 2022 Association of COVID-19 with major arterial and venous thrombotic diseases.

A population wide study of 48 million adults in England and Wales found that the incidence of venous thromboembolism persisted for up to 49 weeks after COVID-19 diagnosis. There was a markedly higher incidence of arterial thromboses in the first weeks after COVID-19 diagnosis compared to no COVID-19 diagnosis, however the risk declined rapidly. The rate of VTEs did not weaken as quickly with a twofold higher incidence of deep vein thrombosis and pulmonary embolism for an extended period of time.

July 2022 Hypercoagulability, endotheliopathy and inflammation approximating 1 year after recovery: Assessing the long-term outcomes in COVID-19 patients.

COVID-19 patients experience hypercoagulability and endotheliopathy up to 4-months after recovery. This study evaluated the haemostatic, endothelial and inflammatory profiles of 39 COVID-19 patients up to 16 months post recovery compared to 124 healthy participants. The cohort consisted of 11 asymptomatic, 19 mild-moderate symptoms, 2 severe and 7 critical patients.

All recovered COVID-19 patients showed significantly higher biomarkers of hypercoagulability, endotheliopathy and inflammation compared to the control group. These findings were associated with thrombin generation showing a higher median endogenous thrombin potential, and the median anti-thrombin levels were also 97% lower in the patient group compared to the controls. Other inflammatory markers were also raised in recovered COVID-19 patients.

Despite this study having a small sample size and used a limited number of parameters and biomarkers, these findings suggest that thromboprophylaxis may be recommended for high-risk COVID-19 patients who show elevated hypercoagulability, endotheliopathy and inflammation biomarkers after recovery. However, the role of extended duration of thromboprophylaxis for this group is controversial and no consensus has been founded.

May 2022 The role of zinc and copper in platelet activation and pathophysiological thrombus formation in patients with pulmonary embolism in the course of SARS-CoV-2 infection.

Recent research connects COVID-19 with coagulation dysfunction, with an increased risk of thromboembolism. C-Reactive protein (CRP) is a substance produced by the liver to indicate inflammation and was linked to higher rates of pulmonary embolism and thrombus formation. Recent studies have shown that COVID-19 promotes coagulopathy through the activation of immune cells in reaction to tissue damage, resulting in thrombosis.

The micronutrients, zinc and copper were shown to present anti-inflammatory and anti-oxidative properties. Their supplementation could possibly improve clinical outcomes in COVID-19 patients. However, high levels of copper may enhance the genetic predisposition to increase CRP, which may trigger inflammation. Also, higher zinc plasma concentration may lessen the interaction between copper and CRP.

Zinc is important in regulating glutathione (an antioxidant) however zinc competes with copper and iron in the cell membrane by inhibiting the enzyme NADPH oxidase. NADPH oxidase is important for the reduction of chronic inflammation and reduces the toxicity of reactive oxygen species (ROS) or free radicals. Zinc is also involved in the blood clotting process, and when zinc in the blood is defective, blood clots can form. Therefore, zinc is important for generating thrombolytic processes during COVID, fibrin degradation, blood flow, ROS generation and restoring blood flow after thrombolysis. The maintenance of ideal zinc levels is imperative for the proper functioning of antioxidant defences.

May 2022 Influence of sex on development of thrombosis in patients with COVID-19.

This observational research aimed to determine if sex was a determining factor for risk of thrombosis among COVID-19 patients. The study group consisted of 1885 men and 1009 women COVDI-19 hospitalised patients from 16 centres across Japan, from April to September 2021.

Mild and moderate levels of COVID-19 were similar between the groups, however, men had more severe COVID-19 at admission, 9.1% compared to women (5.7%). Males also developed thrombosis and received pharmacological thromboprophylaxis more often than females. Understanding that men have more severe COVID-19 than women could be useful in forming a patient-specific optimal management strategy.

April 2022 Persistent lung injury and prothrombotic state in long COVID.

Microthrombus and arteriovenous thrombus play a significant role in the process of pulmonary functional lesions. This review studies the possibility that prothrombotic states, including hypercoagulability and pulmonary vascular endothelial cell (EC) activation, may affect long-term pulmonary symptoms in long COVID.

With regards to pulmonary vulnerability, in the early stage of COVID, damage to the local vascular ECs is difficult to predict, however impairment to these cells often serve as the initial site of thrombosis. This is the stage, activated vascular ECs are frequently ignored, however they are the susceptible basis of long COVID after hospital discharge. The heightened defence system will unavoidably cause tissue damage while killing the virus, along with initiating the coagulation cascade system, activating Factor X and promoting thrombin production, catalysing the conversion of fibrinogen to fibrin and forming pulmonary microthrombi.

Early therapy may be effective in blocking the occurrence of thrombotic events with the early use of anticoagulant and antiplatelet therapy combined. This is an encouraging treatment to reduce the incidence of pulmonary sequelae.

April 2022 Long COVID: The nature of thrombotic sequelae determines the necessity of early anticoagulation.

Ongoing vascular endothelial damage is one of the long-term effects of COVID-19. This damage promotes adhesion and coagulation which results in the impairment of various organ functions. In addition, thrombosis will additionally exacerbate vasculitis contributing to further deterioration. Therefore, “long COVID is essentially a thrombotic sequela”. (sequela refers to a pathological condition which results from a disease)

This review summarises the evidence for coagulation abnormalities associated with long COVID, focusing on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) discharged by various cells can carry SARS-CoV-2 within the circulatory system and attack tissues and organs; and express tissue factor and phosphatidylserine (PS) which can aggravate thrombosis. The determination of the COVID-19 virus makes chronic inflammation and endothelial damage inevitable. (EVs play an essential role in different physiological functions and pathological processes and have been utilised as diagnostic markers and therapeutic tools in several conditions)

Several studies found several vein thromboses (DVT, PE, splanchnic vein) among COVID-19 patients months post recovery. Other research findings after 4 months showed enhanced thrombin-generating capacity and decreased plasma fibrinolytic potential, demonstrating a sustained prothrombotic state.

Other factors include endothelial cell biomarkers such as von Willebrand Factor and Factor VIII which are significantly elevated in recovered COVID-19 patients. Platelets also play a major role as they release a wide variety of molecules at different phases of the disease, with increased PS exposure in platelet extracellular vesicles.

To date there is no effective treatment for long COVID. Investigating the pathophysiological mechanism and impact of long COVID thrombosis will assist with improving an understanding of early antithrombotic treatment and avoid thrombotic sequelae.

April 2022 Risk of venous thromboembolism after COVID-19 vaccination.

This US study looked at the occurrence of VTE before and after vaccination over a 12-month period (November 2020-2021). There were 792,010 participants who had at least one vaccination: Pfizer (452,950), Moderna (290,607) and Johnson & Johnson (48,453) with the average age being 57 years.

Results found that 772 VTE events were recorded 90 days prior to vaccination and 793 (489 had DVT and 426 had PE) events 90 days after a vaccine being administered. The overall incidence rates were similar per 1000 person-years at 4.0 pre-vaccination and 4.1 post-vaccination.

April 2022 Risks of DVT, PE and bleeding after COVID-19.

This study consisted of just over 1 million people who tested positive for SARSCoV-2 between 1 February 2020 and 25 May 2021 in Sweden and a control group of approx. 4 million participants. The results found that after having COVID-19 there was an increased risk for deep vein thrombosis after three months, for pulmonary embolism after six months, and bleeding at two months.

The study also found a higher risk for these conditions in patients with comorbidities or had more severe symptoms associated with COVID-19. Patients who had COVID-19 in the first wave also were at higher risk compared to those in the second wave.

These results provide useful information which could impact recommendations for diagnosis and preventative strategies against DVT, PE and bleeding after having COVID-19.

February 2022 Contribution of the elevated thrombosis risk of males to the excess male mortality observed in COVID-19.

This observational study measured the rate of thrombotic diagnoses among COVID-19 patients during hospitalisation in both males and females and the mortality rate when evidence of thrombosis was present. The study found males had a 35.8% higher rate of receiving a thrombotic diagnosis compared with females. The mortality rate of all patients with a thrombotic diagnosis was 40.0%, more than twice that of patients with COVID-19 without a thrombotic diagnosis. COVID-19 male mortality rate was also higher at 29.9% which could be explained by an increased thrombotic risk.

February 2022 Adenovirus-Based Vaccines and Thrombosis in Pregnancy.

There have been rare cases of thrombosis and thrombocytopenia (TTS) associated with the AstraZeneca and Johnson & Johnson COVID-19 vaccine, which are adenovirus-based vaccines. As most cases of TTS occurs in women of childbearing age, pregnancy as an important risk factor was investigated.

The review included studies from 1966 to 2021 and from 28 studies containing 1731 women. Analysis comprised of adenovirus-based vector vaccines to document cases of thrombocytopenia and coagulopathy. Over this period of time, no coagulopathy events were reported.

January 2022 COVID-19 vaccination and cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) has been reported following COVID-19 vaccination. This observational prospective study aimed to investigate any increased risk to patients with prior CVST after receiving a COVID-19 vaccination.

Of the 62 patients with prior CVST, 43 received Pfizer-BioNTech, 7 patients received Moderna mRNA-1273 and 7 received ChAdOx1 with 5 receiving Janssen Ad26.COV2.S. From these cases, no thrombotic events reoccurred within 30 days after vaccination. Despite the small sample size of this study, the data supports that COVID-19 vaccines are safe in patients who have previously had CVST.

December 2021 Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19.

Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge.

The study found that extended post-discharge thromboprophylaxis with rivaroxaban for 35 days when compared with no anticoagulation, resulted in better clinical outcomes, including a reduction in major and fatal thromboembolic events without increasing major bleeding. (thromboprophylaxis - any preventive measure that reduces the likelihood of the formation of blood clots)

June 2021 - ATAGI & THANZ COVID-19 Vaccine Statement

March 2021 - Message from our CEO

March 2021 - Symptoms of VTE after COVID-19 vaccination

April 2020 - COVID-19 and Thrombosis - International Society of Thrombosis and Haemostasis

March 2020 - Impact on blood transfusions and blood donations

COVID-19 National Guidelines for Public Health Units

These guidelines provide nationally consistent guidance on how to respond to coronavirus (COVID-19).