Tag: blood clotting

New Treatment-resistant Blood-clotting Disorder Identified

Thrombophilia. Credit: Scientific Animations CC4.0.

Researchers at McMaster University have made a groundbreaking discovery in the field of haematology, providing an explanation for spontaneous and unusual blood-clotting that continues to occur despite treatment with full-dose blood thinners.

The discovery, published in The New England Journal of Medicine, is expected to influence how doctors test for, and treat patients with, unusual or recurrent blood clotting, with the potential to improve patient outcomes.

Researchers found this new blood clotting disorder to have certain similarities to vaccine-induced immune thrombocytopenia and thrombosis (VITT) – a rare but aggressive clotting disorder that was caused by certain discontinued COVID-19 vaccines.

The research reveals that certain patients can develop severe blood clotting due to antibodies that closely resemble those that cause VITT, even in the absence of known triggers for such antibodies, such as blood thinners (heparin) or prior vaccination.

The newly identified disorder has been termed VITT-like monoclonal gammopathy of thrombotic significance (MGTS).

“Our study highlights the importance of recognising and diagnosing this new blood-clotting disorder,” said Theodore (Ted) Warkentin, co-first author and corresponding author of the study and professor emeritus in the Department of Pathology & Molecular Medicine at McMaster University.

“By understanding how to diagnose VITT-like MGTS, we can develop more effective treatment strategies that go beyond traditional anticoagulation,” said Warkentin, a hematologist in the Department of Medicine based at Hamilton Health Sciences’ Hamilton General Hospital.

Specialized testing was conducted at the McMaster Platelet Immunology Laboratory within the Michael G. DeGroote Centre for Transfusion Research, the only laboratory in Canada with the full repertoire of testing required to characterize the VITT-like antibodies that target the PF4 protein. Researchers performed a detailed analysis of cases exhibiting unusual blood-clotting despite patients being on full-dose blood thinners, focusing on those patients who had unexplained VITT-like antibodies that were detectable for a year or more.

The analyses identified the presence of M (monoclonal) proteins (which typically indicate plasma cell disorders), and together with the persisting VITT-like reactivities over at least 12 months (which is highly unusual for most anti-PF4 antibodies), thus pointing to an ongoing pathological process rather than a short-term anomaly.

The study included a multinational collaboration, with data collected from five patients treated at institutions in Canada, New Zealand, France, Spain, and Germany.

Collaborator Jing Jing Wang of Flinders University in Australia played a crucial role in proving for each patient that the M proteins are the pathological VITT-like antibodies. Collaborator Andreas Greinacher of Greifswald University in Germany helped in identifying similar cases in his anti-PF4 reference lab.

“The findings of this study underscore our ability to leverage fundamental molecular and biochemical science to unravel disease mechanisms,” said Ishac Nazy, co-lead author of the study and scientific director of the McMaster Platelet Immunology Laboratory and co-director of the Michael G. DeGroote Centre for Transfusion Medicine.

“This approach enables precise patient diagnosis and informs timely treatment strategies, even for previously unidentified diseases, exemplifying true bench-to-bedside translational medicine,” said Nazy, associate professor in the Department of Medicine at McMaster.

A remarkable observation was that each of the patients had failed blood thinning treatment, but they showed some benefit with unusual treatments, such as high-dose intravenous immunoglobulin (IVIG), Bruton tyrosine kinase inhibitors (ibrutinib), and plasma cell–targeted myeloma therapy. The existence of this novel blood clotting disorder has important implications for how health care providers will evaluate patients who develop unusual or difficult to treat blood clots in the future.

Source: McMaster University

Blood Clotting Concerns Resulting in Vaccination Delays

Vaccination programmes are facing increasing delays because of concerns over AstraZeneca’s very rare blood clotting incidents.

Australia and Greece are the latest governments deciding to offer young people alternatives to AstraZeneca’s vaccine. This will delay inoculation campaigns by around a month in Australia, France and Britain. Meanwhile, the World Health Organization said most countries lacked vaccines to cover health workers and others at high risk from exposure to the virus.

WHO Director-General Tedros Adhanom Ghebreyesus said high income countries had on average vaccinated one in four people whilst low income countries the figure was one in over 500.

“There remains a shocking imbalance in the distribution of vaccines,” he told a press briefing on Friday.

The WHO and GAVI vaccine alliance’s COVAX mechanism seeks to secure vaccines for poorer nations. GAVI alliance head Seth Berkley said AstraZeneca’s supply chain had in fact “picked up” when asked whether the vaccine was being shunned.

“As countries decide they are going to prioritise one vaccine or another, that may free up doses, and in so doing we will try to make sure those doses are made available without delay, if countries are willing to make that happen,” he said.

Australia doubled its orders for Pfizer after its health body recommended that people under 50 receive an alternative vaccine. Greece followed Britain’s example in recommending that people under 30 seek an alternative jab.

AstraZeneca said it was working with regulators “to understand the individual cases, epidemiology and possible mechanisms that could explain these extremely rare events”.

Sabine Straus, chair of the EMA’s safety committee, said that the European Medicines Agency (EMA) received reports of 169 cases of the rare brain blood clot by early April, after 34 million doses had been administered.

Most of the cases reported had occurred in women under 60.

On Friday, the EMA said that if a causal relationship is confirmed or considered likely, regulatory action will be needed to minimise risk. It is also investigating Johnson & Johnson’s (J&J) vaccine over reports of blood clots. US infectious disease expert Anthony Fauci however said there were no red flags reported for the J&J vaccine.

The AstraZeneca vaccine is the cheapest and most high-volume vaccine to date to curb the pandemic and avert damaging lockdowns, but supplies have been beset by delays.

However, new data in the EU, beset by delays, showed that the pace of vaccine deliveries was picking up. Germany said it was accelerating inoculations but needed a new lockdown as well.

“Every day in which we don’t act, we lose lives,” Lothar Wieler, president of the Robert Koch Institute, said.

Hong Kong Health Secretary Sophia Chan said the city would defer its order of the AstraZeneca vaccine this year “so as not to cause a waste when the vaccine is still in short supply globally”, adding that the government was considering buying a new, more effective type of vaccine.

All the countries recommending age limits for the AstraZeneca shot have emphasised that its benefits far outweigh the risks of catching COVID for older people. Even so, some people have been put off; in Madrid half of over 60s meant to receive the AstraZeneca vaccine turned up, a day after Spain’s recommendation that younger people get a different shot.

In France, where vaccine hesitancy is high, the top health body recommended that those over 55 who had received a first dose of the AstraZeneca shot get a new-style messenger-RNA vaccine for the second one: either the Pfizer/BioNTech one or Moderna’s.

Source: Reuters