Can Blood Thinners Keep Moderately Ill COVID-19 Patients Out of the ICU?
Posted on by Dr. Francis Collins
One of many troubling complications of infection with SARS-CoV-2, the coronavirus that causes COVID-19, is its ability to trigger the formation of multiple blood clots, most often in older people but sometimes in younger ones, too. It raises the question of whether and when more aggressive blood thinning treatments might improve outcomes for people hospitalized for COVID-19.
The answer to this question is desperately needed to help guide clinical practice. So, I’m happy to report interim results of three large clinical trials spanning four continents and more than 300 hospitals that are beginning to provide critical evidence on this very question [1]. While it will take time to reach a solid consensus, the findings based on more than 1,000 moderately ill patients suggest that full doses of blood thinners are safe and can help to keep folks hospitalized with COVID-19 from becoming more severely ill and requiring some form of organ support.
The results that are in so far suggest that individuals hospitalized, but not severely ill, with COVID-19 who received a full intravenous dose of the common blood thinner heparin were less likely to need vital organ support, including mechanical ventilation, compared to those who received the lower “prophylactic” subcutaneous dose. It’s important to note that these findings are in contrast to results announced last month indicating that routine use of a full dose of blood thinner for patients already critically ill and in the ICU wasn’t beneficial and may even have been harmful in some cases [2]. This is a compelling example of how critical it is to stratify patients with different severity in clinical trials—what might help one subgroup might be of no benefit, or even harmful, in another.
More study is clearly needed to sort out all the details about when more aggressive blood thinning treatment is warranted. Trial investigators are now working to make the full results available to help inform a doctor’s decisions about how to best to treat their patients hospitalized with COVID-19. It’s worth noting that these trials are overseen by independent review boards, which routinely evaluate the data and are composed of experts in ethics, biostatistics, clinical trials, and blood clotting disorders.
These clinical trials were made possible in part by the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership and its ACTIV-4 Antithrombotics trials—along with similar initiatives in Canada, Australia, and the European Union. The ACTIV-4 trials are overseen by the NIH’s National Heart, Lung, and Blood institute and funded by Operation Warp Speed.
This ACTIV-4 trial is one of three Phase 3 clinical trials evaluating the safety and effectiveness of blood thinners for patients with COVID-19 [3]. Another ongoing trial is investigating whether blood thinners are beneficial for newly diagnosed COVID-19 patients who do not require hospitalization. There are also plans to explore the use of blood thinners for patients after they’ve been discharged from the hospital following a diagnosis of moderate to severe COVID-19 and to establish more precise methods for identifying which patients with COVID-19 are most at risk for developing life-threatening blood clots.
Meanwhile, research teams are exploring other potentially promising ways to repurpose existing therapeutics and improve COVID-19 outcomes. In fact, the very day that these latest findings on blood thinners were announced, another group at The Montreal Heart Institute, Canada, announced preliminary results of the international COLCORONA trial, testing the use of colchicine—an anti-inflammatory drug widely used to treat gout and other conditions—for patients diagnosed with COVID-19 [4].
Their early findings in treating patients just after a confirmed diagnosis of COVID-19 suggest that colchicine might reduce the risk of death or hospitalization compared to patients given a placebo. In the more than 4,100 individuals with a proven diagnosis of COVID-19, colchicine significantly reduced hospitalizations by 25 percent, the need for mechanical ventilation by 50 percent, and deaths by 44 percent. Still, the actual numbers of individuals represented by these percentages was small.
Time will tell whether and for which patients colchicine and blood thinners prove most useful in treating COVID-19. For those answers, we’ll have to await the analysis of more data. But the early findings on both treatment strategies come as a welcome reminder that we continue to make progress each day on such critical questions about which existing treatments can be put to work to improve outcomes for people with COVID-19. Together with our efforts to slow the spread of SARS-CoV-2, finding better ways to treat those who do get sick and prevent some of the worst outcomes will help us finally put this terrible pandemic behind us.
References:
[1] Full-dose blood thinners decreased need for life support and improved outcome in hospitalized COVID-19 patients. National Heart, Lung, and Blood Institute. January 22, 2021.
[2] NIH ACTIV trial of blood thinners pauses enrollment of critically ill COVID-19 patients. National Heart, Lung, and Blood Institute. December 22, 2020.
[3] NIH ACTIV initiative launches adaptive clinical trials of blood-clotting treatments for COVID-19. National Heart, Lung, and Blood Institute. September 10, 2020.
[4] Colchicine reduces the risk of COVID-19-related complications. The Montreal Heart Institute. January 22, 2021.
Links:
COVID-19 Research (NIH)
Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) (NIH)
NIH Support: National Heart, Lung, and Blood Institute
Dr. Collins, are there any ongoing trials of treatments for people with “long COVID-19” yet? My 36-yr-old daughter, who was previously quite healthy, has been ill and disabled by her symptoms after getting the disease in March 2020. Thank you for your response.
“In the more than 4,100 individuals with a proven diagnosis of COVID-19, colchicine significantly reduced hospitalizations by 25 percent, the need for mechanical ventilation by 50 percent, and deaths by 44 percent”
Every Hospital, Doctor and Individual should know of these statistics—-This might save thousands of lives.
“If you loose one life you loose a Universe”
Have your clinical trials exposed variance in risk for those individuals with type O blood? The reason I ask is because last Christmas I was with my daughter, husband and their 6 kids. Everyone was ill except my daughter and myself with flu like symptons. The youngest has a strange rash and her husband said he had never felt like this before. Fevers would break and return within hours. Both my daughter and I have type O blood and I remember hearing someone on the news saying that those having type O seem to be at less risk of catching disease. I’ve never heard anything since. Looking back on it with what I know now, I think we may have been witnessing Covid 19. Later, speaking with my nephew, he told me of his family being ill with Covid-like symptoms and he and his youngest daughter who are both blood type O were the only ones not to get ill while the others kept getting it over and over. Could it be the blood type O that saved us?
In the NIH ACTIV trials, have the doctors excluded patients with known thrombocytopenia and Myelodysplastic Syndrome when using blood thinners?
if blood thinner is used, what impact does it have on d-Dimer readings? Would the d-dimer readings still increase for a time before declining showing the blood thinner is reducing the potential for blood clots? Or other items causing elevation d-dimer reading beside blood clotting?
How long does it take for D-Dimer risk or blood clot risk to fade away completely? 3 months?