With the concern of blood clots due to the AstraZeneca vaccine, the issue has been much in the news. The news rarely reports items in much depth, often interviewing contradicting experts. The goal of this report is to give a more in-depth treatment about clots, for the purpose of public education. It is not an issue which would make me, an emergency doctor with some ICU experience, hesitate to get the AZ vaccine for that reason. But what do we know about blood clots?
Blood normally contains several clotting factors to help stop blood loss in the presence of wounds. Genetically, lots of people have defects which predispose to blood clots. 5% of the population have accelerated Factor V Leiden or protein C, which increases risk of a clot 5 to 50 times (if heterozygous CD. Homozygous mutation). Protein C and S deficiencies are less common, 1 in 1500 has an antithrombin III deficiency which causes risk (a homozygous lesion is incompatible with life!). Acquired problems like antiphospholipid syndromes also exist.
Blood clots are more common in patients who smoke, are obese, smoke, exercise little, take hormones such as oral contraceptives or testosterone, have undiagnosed or diagnosed cancer, are pregnant, are immobile, have had surgery or who have a family or personal history, or genetic predisposition. Heart failure, valve problems or fibrillation can cause clots. Many have no findings, but the most common is an ECG showing sinus tachycardia. Smoking while taking OCP over the age of 35 increases risk.
Most people at genetic risk for blood clots do not get them. Most blood clots are not that significant and do not necessarily cause problems. Many known blood clots can be easily treated with anticoagulants. Rarely, filters are used. Surgery is reserved for large and catastrophic clots.
Scores for diagnosing blood clots, such as the (modified) Wells score, are not great. They look fir things like size differential in the calves, history of surgery or cancer, and (oddly) whether the doctor thinks a blood clot is likely. Imaging for blood clots often concentrated on the legs, a positive ultrasound for DVT makes other clots more likely. A nuclear V/Q lung scan is less useful than a CT angiogram where due in the vessels shows clots in the lung or brain of legs most clearly.
Most blood clots in the lung migrate from the thigh or pelvis. Most blood clots in the brain migrate from the heart. If you gave clotting anywhere, there is an increased predisposition or risk factors, so the specific location of the clot may not change that. Emboli are blood clots (thrombi) that migrate, since blood is dynamic.
Blood clots are rarely diagnosed until causing problems like shortness of breath, leg symptoms, fever, cough, headache or “a sense of doom”. They are hard to diagnose. I know an ICU doctor who CT scans all his patients, which is not recommended. In the ER, ultrasounds of the leg are a useful screening test.
Since so many clots are not diagnosed or significant, and since genetic and acquired causes are common, I would not hesitate to get the AZ vaccine if there is a 1:300,000 risk. Likely many of these were caused by other things anyway.
In another thread, I was asked how many women on birth control die from it. That’s a hard question to answer, because clotting is far from the most likely cause of death for people who might take estrogen-containing birth control pills. In fact, pregnancy remains a non-trivial cause of death, although it’s thankfully fairly small these days. I did some quick googling and found that “all cause mortality” was lower (in a largish UK study) for women who ever took BC than for women who never did. But that doesn’t tell you how many of them might have died due to blood clots from the BC. The data is available (I’m pretty sure it used to be included in the package insert with my birth control pills, and especially for women over 35 who smoke, it was something to think about) but I didn’t easily find it.
But similarly, while I think the blood clot issue with the viral-vector vaccines is real, I’m willing to bet the all-cause mortality of people who took those vaccines is lower than for matched people who didn’t – because they are effective at preventing covid. And at the moment that’s unfortunately not all that rare.
It is clear the risk from Covid is dramatically higher than the risk of blood clots. It is not clear wha all the long-term cardiac and neurological risks of having had Covid are, but they seem significant. Since blood clots are so common, under diagnosed, and hard to diagnose, the risk would need a study involving millions of shots. Although millions of vaccinations have been given, most of the blood tests and information needed is unknown. It is safest to conclude there is a very small risk from the vaccine. Medicines like antidepressants also have a very small risk.
The risks are bigger in hormone replacement or oral contraceptives, particularly in young women who smoke. Since the risk is associated more with estrogen than progesterine, and since these doses may differ among different pills - these risks have been quantified but often vary from pills. Again, some of the risk is due to common genetic variability, but that hardly matters to a patient who takes them. I advise everyone to smoke less and exercise more. During Covid, weight control and exercise are often challenging. This pandemic is mentally hard on most people, and stress may be high while motivation is low.
Problems in pregnancy are often related to economic and coverage issues. They are much higher, in many places, than they should be or could be.
It is worth emphasizing most clots cause no symptoms, and most clots which cause symptoms are easily treatable.
Peopke take estrogen both for birth control and for hormone replacement.
In the 60s and 70s, it was found that the high doses of estrogen in birth control caused increases in strokes and blood clots in the legs. Especially in smokers over 35. Lower dose estrogen became the norm and is somewhat safer. Some pooled risk-analyses show no increased risk of stroke in the lower dose estrogen tablets (35mcg, low is under 50mcg). Rates of blood clots to the legs are 3-4 times higher than non-users (and maybe 8 times higher in Factor V Leiden deficiency). Desogestrel and other third-generation contraceptives are safer still. The risk is very low, but current ACOG guidelines do not recommend it in snokers, uncontrolled hypertension, history of clot, migraines or cancer. Excess rates of heart attack (per 100,000 women*years of use) for non-smoking women using low dose estrogen are 0.4/0.6/2 (for 20-24y,30-34y, 40-44 years old). Number of excess pregnancy related deaths per 100,00 live births for these ages are 10/12/45. Barrier contraceptives, spermicides and diaphragms are options. But with the new lower-dose contraceptives increase in mortality is minimal for most people.
The WHI (Women’s Heath Initiative) study around 2000 showed using estrogen for hormone replacement was riskier than thought. Estrogen was used to treat hot flashes, vaginal dryness, vasomotor symptoms and mood changes post menopause. Risks can be reduced by not using continuous estrogen and medoxyprogesterone, lower doses, local creams or alternatives such as antidepressants. HRT is no longer a first line treatment and some people should not take it.
Again, most clots are not clinically significant. Most are not diagnosed. Most do not increase mortality.
Thank you for this. My province just lowered the age today, and based in part on reading this thread my spouse & I are booked to get the A-Z shots tomorrow.
The legs contain both deep veins, which “go to the heart and lungs”, and superficial veins, which stay close to the skin. Clotting in superficial veins may be visible, and are commonly seen in varicose veins. These are of cosmetic concern to some people, but do not increase risk or mortality. Clots in the deep veins can be seen on ultrasound. These can be concerning, as they can travel to the lungs. Again, small clots in the lungs may not cause any synptons. Large ones can be very dangerous.
Strokes occur when part of the brain is not getting oxygen for an extended period of time. These strokes can be caused by several things, including embolic blood clots usually from the heart, or local thrombi. (Other causes include bleeding from trauma, aspirin, aneurysms and so forth). They tend to occur in different locations.
I think it is quite unfortunate how many jurisdictions have stopped administration of the AZ and J&J vaccines based on the blood clot concern. I crunched some quick numbers for the 18-29 demographic based on the CDC’s site: for the lowest risk adult age group (18-29), there have been 2,186 deaths out of 5.5 million cases, so one death per 2,516 cases. I’ve read that the prevalence of blood clots for the J&J vaccine has been ~1 per million vaccines administered, and potentially as high as 5 per million for AZ - so at worst, 1 incident of blood clots per 200,000 vaccines administered. Even if 100% of blood clots led to death, it seems like it’s basically two orders of magnitude more risky to get COVID than to get the AZ vaccine.
So even if you were solely a selfish adult in the lowest-risk demographic looking out for yourself - you’d have to think your chances of getting COVID are less than ~1.3% for you to have a greater chance of dying from the vaccine than from COVID. In a lot of western countries right now that’s you’d probably exceed that chance of getting COVID within a couple months at most. Given the benefits to the greater population from higher vaccination rates, it seems troubling to me that governments have made the decision to stop the administration of these vaccines. It seems almost certain to me that more people will die from delay of vaccine rollouts than would be saved by preventing blood clots.
Apparently, the J&J pause was intended to make sure that all doctors (especially in emergency rooms) know to check for platelet levels of this type of clot is suspected, because it needs to be treated differently from ordinary clots.
I’m pretty sure I heard on NPR today that they anticipate reauthorizing the J&J vaccine on Friday, possibly with some new warnings or restrictions. Since most states do have a lot of other vaccine available right now, it wasn’t terribly costly in terms of man-days unvaccinated to pause it.
My son’s first dose was delayed 5 days. A friend’s son’s only two days, as two data points. Yes, it’s longer until they are “fully vaccinated”, but the protection you get two weeks after one dose of Moderna is comparable to what you’d have gotten from J&J, so the human cost of the pause was fairly low.
I would guess/estimate that perhaps under 5% of blood clots lead to death in younger people. Certainly nothing close to 100 percent. Others would put this risk at 10-30 percent based on deaths in older people who have symptomatic DVT causing enough symptoms to be diagnosed. They likely have many more risk factors. I maintain many cases are transient and subclinical, certainly never diagnosed or causing symptoms.
I’m not sure it is that clear that this needs to be treated differently from other clots on the basis of this article. The article implies giving heparin may make things worse. The fact remains that even in vaccinated patients, other clot causes are still likely unless extremely closely linked in timing.
Coagulation disorders are tested by checking platelet counts, which might be lowered by aspirin or in disseminated coagulation, PT, INR, factor levels, protein C and S, factor V Leiden and antithrombin. As a screen, the first few tests give a good start. Although there are several types of thrombophilia, doctors know how to treat them.
Everything I’m reading suggests that the usual first-line response to clots is heparin, and heparin will exacerbate these particular clots. And that there are other available treatment for clots, and that if a patient presents with a clot serious enough to need treatment shortly after vaccination, they should be tested to see whether heparin is good or bad prior to initial treatment.
fwiw, when my mother had a leg scan revealing a massive clot all through the vein in one leg, they hospitalized her and pumped her full of heparin before doing much of anything else. (which worked well for her, and she’s pretty much recovered.)
The usual response to clots is to treat and try to determine the cause; doing blood work to check the relevant hemological parameters. Very late in the game, clots can cause lack of pulse, coldness (“polar”), paralysis, pallor (pale skin) and numbness (“parasthesia”). In the absence of these things, clots may be concerning and treatments may be started - but there is almost always time to do blood work before treatment. Treatment might be oral with aspirin or Coumadin. These take days to work, so it is more likely treatment would be started with parenteral unfractionated heparin (UFH) or better, various synthetic low-molecular weight alternatives to heparin such as dalteparin or Enoxaparin.
The PT (prothrombin time) blood test measures factors I, II, V,VII and X in the coagulation cascade (“the extrinsic pathway”). The PTT (partial) measures these plus factors XI and XII. Heparin affects factors IIa and Xa, (which convert to II and X), and so both the PT and PTT (PT is sometimes “normalized” and called the INR) are monitored in all cases of heparin treatment.
Since thrombocytopenia (low platelets) is a fairly common immunologic reaction to heparin which lowers platelets, it should possibly be avoided for Covid. Since this is not rare, it is unclear if Covid causes this. It may be easy enough to give synthetic LMWHs (low molecular weight) heparin such as dalteparin or Lovenox (enoxaparin) instead when supplies permit. But in any case, the platelets would still be monitored post treatment and platelet transfusion is reserved for counts below 10-50 depending on circumstances.