Blood Clots, COVID-19 Vaccines, and Pregnancy

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You may know that pregnancy raises the risk of developing blood clots, as do oral contraceptives. You may also may know that the elevation of the risk rises substantially if you smoke too. Consequently, you may be all the more concerned hearing recently that health authorities are investigating a possible association between blood clots and the AstraZeneca COVID-19 vaccine that has been the mainstay vaccine in many countries. More recently, a handful of cases —six as of April 13, when I am writing this— of the same category of blood clot have been found in US women in the 18-48 year age group who received the Johnson and Johnson (Janssen) COVID-19 vaccine between 6 and 13 days after vaccination. As a result of these 6 cases, on April 13, the administration of the Janssen COVID-19 vaccine was paused in many US states, potentially delaying vaccination to millions of people. Although 6 cases (there may be more by the time this article is published) are not enough to draw any conclusions, a red flag is raised because the type of clotting disorder is like the clotting disorder that has been of concern in connection with the AstraZeneca COVID-19 vaccine, where it seems that the risk of blood clots is increased especially in middle age people. Another red flag is raised because the Janssen and the AstraZeneca vaccines work through the same mechanism. They are both viral vector vaccines, each using a different type of adenovirus to carry DNA that encodes the spike protein that SARS-CoV2 (the virus that causes COVID-19) displays on its coat and that the virus uses to attach to a protein called ACE-2, present on many times of body cells. Important to our discussion today, the clotting disorder being studied in connection with these two viral vector vaccines is different from the fairly common type of clotting whose risk rises with pregnancy and with oral contraceptive use, so let’s unpack the difference now.

When you are pregnant, when you have given birth within the past few weeks, when you are taking oral contraceptives, when you are smoking, and especially when you are smoking and using oral contraceptives, you become particularly susceptible to the formation of clots within deep veins of the legs and pelvis. This happens because of three factors:

  1. Increased activation of blood clotting systems
  2. Slowing or stopping of movement of blood (in pregnancy, due to the growing womb pushing on pelvic deep veins, and
  3. Damage to blood vessels— known together as the Virchow triad, named for Rudolf Carl Virchow (1821-1902), a pioneer in medicine, pathology, and anthropology.

In addition to causing pain and inflammation in the region of the clot, such as in the leg, such a blood clot —known as a venous thrombosis— can generate emboli, pieces of the clot that travel in the veins.

This can lead to an embolism, a clot in a distant site, caused by an embolus getting stuck. Generally, this happens in the lungs, where it’s known as a pulmonary embolism, which is treatable, but it must be detected early, or it can threaten life.

In contrast, the clotting of concern with the two viral vector vaccines is part of a condition characterized not only by an increased tendency to form clots but also a depletion of cell fragments called platelets. The job of platelets is to form clots and, when their numbers drop below a certain number, the person is said to have thrombocytopenia, a low platelet count. Now, it may seem counterintuitive that there are conditions in which the blood forms clots in connection with the number of platelets decreasing. Such conditions are what doctors call “consumptive coagulopathies”: the number of platelets in the blood decreases, because platelets are clumping together with one another, forming clots, and getting consumed in the process. When this happens, one of the places where clots can form is within channels known as venous sinuses that course through the connective tissue layers that surround the brain. Known as cerebral venous sinus thrombosis (CVST), this rare type of blood clot, occurring together with thrombocytopenia, is what the 6 cases in the United States after the Janssen vaccine have been, as have many of the clotting cases of concern related to the AstraZeneca vaccine.

As for why this is happening —if indeed there actually is a causative connection with the viral vaccines, which we cannot yet say that there is— there are several hypotheses, some of which are rather farfetched. One hypothesis that has been cited, for instance, in connection with a study from Denmark, is that clotting is a rare adverse effect of the vaccine being injected inadvertently into a vein, rather than into the muscle tissue of the deltoid muscle in the shoulder. In connection with this, there have been discussions about whether vaccinators should aspirate —pull back the plunger of the syringe for a few seconds to make sure that blood does not enter the syringe— before injecting. However, guidelines from many health authorities, including the US Centers for Disease Control and Prevention (CDC), discourage aspiration because it may cause sheering by the needle, increasing pain and other discomfort. Thus, in this photo of me receiving the Pfizer-BioNtech vaccine this past February, notice that the vaccinator is holding the syringe with just one hand, his index finger on the plunger, indicating that he has not aspirated, as doing so requires two hands on the syringe in order to pull up on the plunger.

There is a triangular shaped area on the deltoid, considered to be a safe zone, where the injection is made with the objective of hitting pure muscle, avoiding blood vessels and nerves. Veins are a bigger concern than arteries, because veins carry whatever is injected away from the site into the general circulation, from which what was injected (or a clot formed from it) would reach the lungs. This makes a particular vein, called the “humoral circumflex vein”, the main concern as a blood vessel to avoid, but this vein is located very deep into the muscle going around the humorous bone. Thus, even if you are trying to reach this vein, the only way to do so would be to use a needle longer than the one that you are supposed to use, and to push it in really deep. The vaccinators are well trained and are given only the correct needles (the short type). The only challenge is the possibility of the opposite scenario, where an obese individual with a thick layer of fat beneath the skin needs to be penetrated so that the needle reaches actual muscle.

More plaussible is that in a very small number of people, the viral vectors may cause an immune reaction similar to a very condition that has been documented with a drug called heparin that is given to keep blood from clotting. While heparin works against clotting, in this very rare condition, heparin combines with a certain protein from platelets. The resulting combined molecule is seen by the immune system as something foreign, causing production of antibodies that make platelets attach to one another, causing clots while consuming platelets, sometimes dropping the platelet count so much that the same person also suffers from bleeding. We hope that this is not happening with the Johnson and Johnson vaccine. At the time that I’m writing this, there really aren’t enough data to know, so stay tuned.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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