This article was reviewed by Dr. Zachary Benet, one of our subject matter experts.
The paper we’ll be demystifying can be found here if you’d like to follow along!
This research was conducted by a group of researchers from the Netherlands. The corresponding author is Dr. Erik Klock.
Patients with COVID-19 infections face a variety of risks, many of which are still being studied. COVID-19 may increase the risk of developing blood clots in both veins and arteries (venous & arterial thromboembolism). This prevents regions of the body from getting proper blood flow and this is dangerous if it affects a large area or vital organs such as the heart, lungs or brain.
So why does this happen? This increase may be due to a variety of factors including high levels of inflammation, low oxygen levels (hypoxia), lack of movement (immobilization), and/or a condition where small blood clots form throughout the body (disseminated intravascular coagulation, or DIC). With DIC, proteins in the blood (which normally form clots to help stop bleeding), may become unusually active and form clots unnecessarily.
What we did not know was how often these issues occur. This information is important because it helps doctors figure out when to give preventative medication, especially in patients who are admitted to the intensive care unit (ICU) as they have a much higher risk of developing blood clots.
In this paper, the researchers looked at all patients with COVID-19 that were admitted to the intensive care unit (ICU) of two Dutch university hospitals and one teaching hospital. The researchers were looking for how often there was a case with a particular issue from a list of issues. The five issues they were on the lookout for are:
- If one or more obstructions formed in a lung artery, and the patient was also showing symptoms (this is called symptomatic acute pulmonary embolism)
- If one or more obstructions formed in one of the large veins (this is called deep-vein thrombosis)
- If an obstruction formed in an artery leading to the brain, potentially blocking the flow of blood to the brain (this is called ischemic stroke)
- If a clot formed in a heart artery and blocked blood supply to heart muscle, which commonly leads to a heart attack (this is called myocardial infarction)
- If a clot or obstruction interrupted blood flow to an organ or body part (this is called arterial embolism)
If any of these issues were seen, the case was counted as being a part of something called a “composite outcome”.
Basic statistics: an overview
|These two values make up the “95% confidence interval” range for a specific measurement. This range says that if a number of other similar studies were completed, then the value of this measurement will be within that range 95% of the time!|
|To get this range, a set of data is sorted to be in increasing order, and divided into four equal sections. The IQR is the range between the start of the second section, and the end of the third section.|
ex. 1, 3, 4, 5, 6, 7, 8, 9, 11, 13, 15
1, 3, 4, 5, 6, 7, 8, 9, 11, 13, 15 IQR = 11 – 4 = 7
- The “index date” was the date when the patient was admitted to the ICU.
- The researchers checked on the patient until they were discharged, until death, or until April 5th 2020 (whichever came first).
- They looked at 184 patients who were confirmed to have COVID-19. Of these patients, 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still in the ICU on April 5th 2020.
- The median time spent observing each patient was 7 days (IQR 1-13).
- Everyone got at least a normal dose of medication that reduces the chance of forming blood clots (thromboprophylaxis), and some doses increased over time.
- Diagnostic tests were only performed if professionals suspected blood vessel obstructions in the patient.
Overall, one of the issues from the list was seen in 31% of patients (CI of 20% – 41%). Out of this, 27% (CI of 17% – 37%) had clots in veins, and 3.7% (CI of 0-8.2%) had clots in arteries. Obstructions of lung arteries were the most common and made up 25 cases (81%).
Can we predict these issues?
A hazard rate can be thought of as how often something happens, and these rates can be compared between two groups to make a ratio. Here, researchers compared using age (age-adjusted hazard ratio, or aHR). Prothrombin time (PT) and Activated Partial Thromboplastin Time (aPTT) are blood tests that measure how long it takes for a clot to form. If the PT time was >3 seconds or aPTT time was >5 seconds, the researchers defined this as “coagulopathy.” Coagulopathy is a condition where clots are not formed properly. The researchers found that the age-adjusted hazard ratio and coagulopathy could each be used to predict issues related to blood vessel obstructions.
The 31% rate of blood vessel obstruction related issues indicates that ICU patients with COVID-19 have a high risk of these events, even when they are given medicines typically used to prevent clotting. This rate is similar to rates of blood vessel obstruction in patients with a condition in which small blood clots develop throughout the bloodstream called disseminated intravascular coagulation (or DIC), even though none of the patients actually developed DIC.
The paper notes that as most of the patients were still in the ICU when the study ended, they were at risk of developing further issues. This means that this 31% rate might have been a low estimate. The paper also notes that as it is difficult to do imaging tests on intubated patients in isolation. If such tests had been performed, they may have discovered even more cases. Due to the nature of this study, they could not account for how the differences in treatment from patient to patient may have affected outcomes.
It’s important to note that while this paper highlights a risk factor for healthcare professionals to keep in mind while treating COVID-19 patients in the ICU, it is not without limitations. The paper notes that further study is needed to determine the effect of adjustment to the treatment procedure used upon admission to the ICU, including drug dosages. As the study notes, most of the patients were still in the ICU when the study ended and may have developed further issues afterwards. Similarly, as they only looked at patients suspected of developing clots, there may have been clotting that was not noticed just yet. Future research would also need to look carefully at which patients develop blood clotting or DIC, as mild and severe infections may have different effects.
While this paper found a high percentage of patients with these blood clot issues, it is a lot more difficult to determine exactly what treatments are appropriate for these COVID-19 patients. Healthcare professionals will need to carefully make adjustments based on these risks, and work out a delicate balance with the medications they prescribe. With more study and testing, the healthcare community will be able to develop better protocols. In the meantime, doctors should definitely be on the lookout for signs of blood vessel obstruction issues and continue to order diagnostic tests and treat with appropriate, medically recommended medication.