Acute Thrombocytopenic Purpura, the MMR and Natural Infection

Twitter's a great tool for rapidly disseminating information. With a large network of followers, a simple message can spread like wildfire. This can be great for getting important facts out to a wide audience, like instilling a bit of rationality around the fear-infused media exaggerations of the events at the Fukushima Daiichi nuclear plant in Japan.

Of course, like all decent tools, there can be a bad side to Twitter, as well. Just as rational facts can be spread quickly, so, too, can misinformation. Given the character limits on tweets, a lot of the nuance and complexities of a given subject are often left out, resulting in messages that, on the surface, may instill readers with a sense of unease or outright anger. The careless may inadvertently scare people about a certain topic, while the nefarious use the limitations of Twitter to their advantage, purposefully spreading partial-truths or even outright lies to promote their agendas.

Such was a tweet I saw just the other day.

A certain California doctor that we all know and love retweeted something from the Twitter bot @VaxCalc. The person who set up that account uses it to spread half-truths and fear about vaccines. Their sole purpose, it seems, is to misinform people about immunizations. To what end, one can only guess. At any rate, the aforementioned pediatrician passed along the following:

That sounds pretty bad. I mean, bleeding into the skin? And less than 1% of that is reported to VAERS (Vaccine Adverse Event Reporting System)? Reading that, it sounds like acute thrombocytopenic purpura is a horrible, horrible reaction and that it actually happens quite frequently after receiving the MMR. Further, our friendly neighborhood pediatrician to the stars added his own comment of "Not great medicine" when he retweeted @VaxCalc's note:

Well, between the two of them, they got me to wondering: first, what the heck is acute thrombocytopenic purpura (ATP)? Second, how often does it occur following MMR? Third, how often does it occur following measles (or other viral illnesses)? Since @VaxCalc is just a bot, and because the good doctor decided to share with his nearly 11,000 followers this tidbit of information, I decided to ask that third question. I mean, since he commented that either ATP after MMR is not good medicine or the reporting rate is not good medicine, then he must know how often it occurs after infection, right? I mean, if he didn't put the information in context, well, that might be considered either intellectually dishonest or, to be charitable, sloppily lazy.

He hasn't answered me yet, other than to ask "what's ATP in that context?" Because, y'know, it's really difficult to look at the tweet to which I was replying.

That had the benefit of forcing me to look for the answer myself. Actually, I started looking for the answer right away, figuring that I wouldn't get a straight answer from the fellow. So off we go on a merry literature-reviewing adventure, but first, a quick note about VAERS.

VAERS

The Vaccine Adverse Event Reporting System is a passive surveillance system. As its name implies, it records reports of adverse events following the administration of vaccines. It's important to note that VAERS tracks adverse events, not adverse reactions. Though similarly named, these two terms have distinct meanings. An adverse event is any unfavorable or unintended event following administration of a medical product; there is a temporal connection, but not necessarily a causal connection. By contrast, an adverse reaction is an adverse event which has a reasonably causal relationship to the medical product. So that's the a significant limitation of VAERS. There's a lot of noise, lots of events that, in the end, have no causal connection with a vaccine. The biggest limitation, though, is that it is a passive system, meaning that no one is forced to report each and every occurrence of an adverse event (AE). You may wonder, well, why not? Because anyone can submit a report to VAERS - pharmaceutical companies, physicians, researchers, even regular Joes like me. The makers of medical products are required by law to report all AEs to FDA, but it's kinda hard to enforce that for every single person in the U.S. That said, it's not any huge surprise that there is underreporting.

The take away is this: VAERS is a system for raising questions and looking for trends. It is not a definitive source for data. It's a springboard, not a finish line.

Now, onto the meat of this whole mess.

Acute Thrombocytopenic Purpura

Thrombocytopenic purpura is a blood-clotting disorder in which the body makes antibodies against its own platelets. This results in the destruction and elimination of platelets, the parts of your blood that cause clotting and help you stop bleeding if you get cut. So, the "thrombocytopenic" part describes a reduction in the number of platelets and "purpura" refers to the purplish discoloration or bruising that may result. Acute means that it comes on quick and doesn't last very long. Now, just because it doesn't last all that long does not mean that it is not serious. ATP could potentially lead to hemorrhage or other dangerous effects from excessive bleeding.

ATP and the MMR Vaccine

So what does ATP have to do with the MMR vaccine? Well, thrombocytopenic purpura is a known risk of the vaccine. Numerous studies have looked at ATP (also referred to as immune thrombocytopenic purpura, or ITP). To keep matters simple, I'll convert all rates to # per 100,000. France, et al. (2008), found a rate of about 2.5 per 100,000; Peltola, et al. (1994), found 3.3 per 100,000; and Black, et al. (2003), put the risk at around 4 per 100,000. Mantadakis, et al. (2010), performed a systematic review of 12 studies, finding that ATP following MMR occurred from 0.087 per 100,000 to 4 per 100,000, with a median of 2.6 cases per 100,000 vaccine doses. In fact, the CDC even acknowledged in one of their MMWR reports (1998) that it occurs and that it should be considered when deciding whether or not to vaccinate a child with a history of thrombocytopenic purpura:

Children who have a history of thrombocytopenia or thrombocytopenic purpura may be at increased risk for developing clinically significant thrombocytopenia after MMR vaccination (172,175). Although thrombocytopenia can be life threatening, no deaths have been reported as a direct consequence of vaccine-induced thrombocytopenia. The decision to vaccinate with MMR should depend on the benefits of immunity to measles, mumps, and rubella and the risks for recurrence or exacerbation of thrombocytopenia after vaccination or during natural infection with measles or rubella. The benefits of primary immunization are usually greater than the potential risks, and administration of MMR vaccine is justified, particularly with regard to the even greater risk for thrombocytopenia after measles or rubella disease. However, avoiding a subsequent dose of MMR vaccine may be prudent if an episode of thrombocytopenia occurred within approximately 6 weeks after a previous dose of the vaccine. Serologic evidence of measles immunity among such persons may be sought in lieu of MMR vaccination.

Keep in mind that the CDC's statement is from 1998. Lots of research has been done since then. As the Mantadakis review shows, "MMR vaccination of unimmunized patients with ITP and revaccination of patients with prior ITP did not lead to recurrence of thrombocytopenia," and around 93% recovered within 6 months.

We have, then, a known risk of thrombocytopenic purpura following MMR vaccination. It occurs at a rate of roughly 2-4 per 100,000 doses. In the majority of cases, it resolves on its own, with no lasting problems and is generally not life-threatening. This is something that we should strive to improve on, but it isn't necessarily a deal-breaker in the decision to vaccinate or not. We also need to consider how frequently ATP occurs after infection.

ATP and Infection

Now we get to the question that I asked Dr. Jay: what is the rate of acute (or idiopathic) thrombocytopenic purpura following natural infection? Information on the rate of ATP following infection was a bit more difficult to find. In 1951, Fisher and Kraszewski (PDF) described two cases of thrombocytopenic purpura following natural measles infection. Cines, et al. (2009), describe numerous causes of TP, including autoimmune disorders (e.g., lupus) and chronic infections (HIV, Hepatitis C, H. pylori), as well as following natural infection with rubella, varicella zoster virus (chicken pox) and many other viruses. Yenicesu, et al. (2002), found that following viral infection, ITP occurred about 13.3% of the time. Likewise, Rajantie, et al. (2007) found that thrombocytopenic purpura occurs more frequently following natural infection than after immunization, and that vaccien-associated TP is generally mild and resolves within 6 months in about 90% of cases. Ünal, et al. (2009), also describe mumps as a cause of ATP. Tucci, et al. (1980) discovered subclinical thrombocytopenic purpura in 55% of children with measles, 25% of children with mumps and 30% of children with rubella, among other viral causes. Finally, in the same CDC report stating that ATP occurs in about 1:30,000-1:40,000 (~2-4:100,000) cases following vaccination, it was also reported that ATP occurs in about 1:3,000 (33:100,000) cases of rubella.

By looking at the collection of the literature on the topic, then, we can see that thrombocytopenic purpura occurs at a much higher clinically significant rate (at least 10x more frequently) following natural infection with the viruses against which the MMR offers protection than from the vaccine itself.

MMR Vaccine vs. Measles, Mumps and Rubella

On the one hand, we have a vaccine which carries a risk of acute thrombocytopenic purpura, which typically resolves within 6 months or less, in about 2-4 for every 100,000 doses administered. By contrast, each separate disease (measles, mumps and rubella) individually carry a higher risk of ATP, with similar outcomes as the vaccine. As an example, rubella occurs around 10 times more often following natural infection (~33 per 100,000 cases) than the rate from the vaccine.

Although thrombocytopenic purpura associated with the MMR vaccine is generally mild and resolves without complications, further study to determine why it occurs and how to minimize the risk is certainly called for. However, though we acknowledge that the risk exists, and that we should strive to make the vaccine safer in this aspect, we also must recognize that natural infection with measles, mumps or rubella carry a greater risk than the vaccine. Looking at the risks of both the vaccine and natural infection, the chances of acute thrombocytopenic purpura are reduced with vaccination.

I have to thank Dr. Gordon. If he had not passed on a biased and incomplete view of vaccines and not bothered to even attempt to answer the question I posed to him, I might not have put in the research to figure out the answer to my question. Thanks to Dr. Gordon, when looking at ATP, I was able to discover not only the rate following vaccination and natural infection respectively, but also that vaccination mitigates the overall risk. As I said before, the rate at which ATP follows vaccination should be improved, but it should not be used to dishonestly sway anyone away from the MMR. To do so is nothing but base manipulation.