COVID-19 typically affects the lungs and airways, however, in addition to respiratory problems, about 16% of people hospitalised with COVID-19 experience problems with their blood and blood vessels, leading to blood clots forming in the arteries, vein and lungs. These blood clots can break loose and travel to other parts of the body, where they may cause blockages leading to heart attacks or strokes. Nearly half of all people with severe COVID-19, in intensive care units, may develop clots in their veins or arteries.
What are blood thinners?
Blood thinners are medicines that prevent harmful blood clots from forming. However, they may cause unwanted effects such as bleeding. Some guidelines recommend giving blood thinners when people are first admitted to hospital with COVID-19, to prevent blood clots from developing, rather than waiting to see if blood clots develop and then treating them with blood thinners.
What were the review questions?
A team of Cochrane authors wanted to know whether giving people hospitalised with COVID-19 blood thinners as a preventive measure, reduced the number of deaths compared to people who received no treatment or who received a placebo treatment. They also wanted to know whether these people needed less support with breathing, whether they still developed harmful blood clots, whether they experienced bleeding and whether they experienced any other unwanted events (for example, nausea, vomiting, kidney problems and amputations).
What were the methods?
They searched for studies that assessed blood thinners given to people hospitalised with COVID-19 to prevent blood clots. Studies could be of any design as long as they compared a blood thinner with another blood thinner, no treatment or a placebo (sham). Studies could take place anywhere in the world and participants could be any age as long as they were in hospital with confirmed COVID-19 disease. The search was completed on 20 June 2020.
What did they find?
The authors hoped to find randomised controlled trials (RCTs). RCTs allocate participants at random to receive either the treatment under investigation or the comparison treatment (another treatment, no treatment or placebo). RCTs give the best evidence.
They did not find any RCTs, so they included seven non-randomised ‘retrospective’ studies that looked back at treatments given to 5929 people. These studies took place in intensive care units, hospital wards and emergency departments in China, Italy, Spain and the USA. They provided evidence on deaths and bleeding but no evidence on respiratory support, blood clotting and other unwanted effects. The studies were very different from each other, so we were not able to pool their results.
Blood thinners compared with no treatment (6 studies)
- One study reported a reduction in mortality and another study reported a reduction in mortality in severely ill people only. Three studies reported no difference in mortality and the remaining study reported no deaths in either group.
- One study reported major bleeding in 3% of participants who received blood thinners and 1.9% of participants who did not receive blood thinners.
Treatment dose of blood thinners compared with preventive dose (1 study)
All the participants were in the intensive care unit on mechanical ventilators. They may or may not have had blood clots but were given either blood thinners in a dose usually used to treat clots (higher dose), or a dose used to prevent clots (lower dose).
- This study reported a lower rate of death in people who received the treatment dose (34.2%) compared with the preventive dose (53%).
- This study reported major bleeding in 31.7% of participants who received the treatment dose compared with 20.5% of those who received the preventive dose.
How reliable is this evidence?
We do not know whether blood thinners are a useful preventive treatment for people with COVID-19 because we are very uncertain about the evidence. None of the studies randomised participants and all were retrospective. Also, they reported different results from each other and did not report their methods fully. This means our confidence (certainty) in the evidence is very low.
What happens next?
The searches found 22 ongoing studies, 20 of which are RCTs, with 14,730 people. Ronald Flumignan, MD, PhD from the Department of Surgery, Division of Vascular and Endovascular Surgery at the Universidade Federal de São Paulo in São Paulo, Brazil and lead author of this Cochrane Review says, "At the moment we are not sure whether this treatment may help prevent the dangerous clotting we see in some COVID-19 patients, but we identified several ongoing studies. We will update our review as new results from these studies become available, and in time we hope we will be able to answer this important question.”
Lead author, Ronald Flumignan from the Federal University of Sao Paulo in Brazil describes what they found in this podcast.