AstraZeneca and blood clots...

By now, I'm sure you've seen the news.

What happened?

7 people (aged 20-50) in Germany developed severe blood clotting disorders (called thrombosis) after receiving the AZ vaccine. 6 of the 7 people (all young women) had a particularly rare form of thrombosis called sinus vein thrombosis. The 7th person had something very similar. 3 of the 7 people have since died. To date, 1.6 million people in Germany have had the AZ vaccine.

What are authorities doing?

AZ vaccinations have temporarily stopped in a number of countries, including Germany. The European Medicines Agency (EMA; basically the FDA in the United States) is reviewing the evidence and “has called an extraordinary meeting on Thursday 18 March to conclude on the information gathered and any further actions that may need to be taken.”

Basically, scientists are trying to figure out whether this is a real safety signal or just noise. We know that correlation does not imply causation (I’ve talked about this before with the Norway nursing home deaths, ice cream sales and drownings). But, at the same time, we can’t undermine the importance of investigating causation, especially for specific events like this.

So, how do we investigate causation?

Well, it’s not easy. And we never “truly” know whether A causes B in epidemiology. But we can use tools, like the Hill’s Criteria of Causality, to help guide us—basically a checklist we use to answer questions like: “Does the AZ vaccine cause rare blood clots”? I imagine this is the type of conversation happening behind closed EMA doors.

1. Strength of the Association- Are blood clots happening at a higher rate among the vaccinated group compared to in the general public? PEI (Paul-Ehrlick Insitut in Germany) did run their numbers on what they would expect in the general public. For 1.6 million Germans, they would expect 1 case of sinus vein thrombosis. 7 were observed. Thus, there is a higher than expected rate, which initiated the suspension of AZ distribution yesterday.

2. Consistency-Did the AZ vaccine cause blood clots during clinical trials? I pulled the EMA report, which showed that 12 people had thrombosis events during the AZ clinical trial. However, 4 were in the vaccine group and 8 were in the control group, so there was no unusual pattern for safety concerns. We also don’t know if these were specifically “sinus vein thrombosis”.

The next question… Is the AZ vaccine causing blood clots just in Germany? If that’s the case, maybe it’s due to something else (like type of reporting, environment or genetics). Or is it happening in other countries too? I imagine EMA is pulling thrombosis reports after AZ vaccination in all countries to adequately answer this question.

3. Temporality- Did the blood clots happen after the vaccination? Yes, they happened between 4-16 days after AZ vaccination. This is an easy one to check off.

4. Biological Plausibility- Is it biologically possible for this vaccine to cause thrombosis? In other words, from our understanding of the human body, could this happen? This is one of the most important questions to answer. I don’t know what the answer is, but I do know that we saw 15 thrombosis events in the vaccine group vs. 10 events placebo during the J&J trial (which is the same “type” of adenovirus vaccine) in the United States. So there may be a link here.

5. …There are more criteria, but you get the point.

Bottom line: Determining causality is very difficult, but we will know a lot more on Thursday morning after the EMA meeting. If scientists do find a link, this will likely be listed as a warning on the vaccine label (like how we see thrombosis warnings with some birth control medications).

Love, YLE