为什么有些人在接种阿斯利康疫苗后出现血栓——新线索

概要

阿斯利康与牛津大学合作开发的疫苗是一种针对新型冠状病毒的腺病毒疫苗。该疫苗通过将指令输送到人体细胞中，以产生针对新型冠状病毒的抗体。然而，这种疫苗带来了一些严重的不良反应。约五万分之一的接种者出现了血栓，这种血栓综合征被称为疫苗诱导的免疫性血栓性血小板减少症（VITT）。

VITT的主要原因是免疫反应出现问题，人们产生的抗体可以粘附在人体自身的一种蛋白质上，这种蛋白质称为血小板因子4 (PF4)。在感染过程中，作为免疫反应的一部分，许多人会产生粘附PF4的抗体，但这些抗体通常粘附力较弱。在VITT中，形成的抗体可以像强力胶一样粘附在PF4上。这些抗体将PF4分子粘合在一起，形成称为“免疫复合物”的大型结构。这些复合物结合并激活称为血小板的小细胞，这些细胞对于血液凝固至关重要。正常情况下，血小板在不活跃状态下漂浮在血液中，但一旦激活，它们就会散开，变得非常粘，并喷出数百种不同的化学物质。在VITT中，血小板被强烈激活，从而导致血栓。血栓通常会影响大脑周围的静脉，这是一个非常不寻常且罕见的血栓部位。许多患者者仍存有终生的残疾症状。

目前已经发现了一种遗传线索可以解释为什么有些人会患VITT。产生部分抗体的基因变异与VITT有关，这种情况在欧洲人后裔中更为常见——欧洲人患VITT的风险似乎更高。肯定还涉及其他基因，但很难找到线索。在英国，科学家已经对200多名VITT患者进行了DNA测序，预计很快就会有结果。然而，尽管存在这些线索，仍需要更深入地了解VITT的原因和潜在的治疗方法。

总之，阿斯利康与牛津大学合作开发的疫苗带来了严重的副作用。需要更深入地了解这些副作用的原因和潜在的治疗方法，以更好地保护接种者的健康。同时，也需要更全面地评估其他疫苗的安全性和有效性，以确保人们的健康得到最大程度的保护。

Why some people got blood clots after the AstraZeneca vaccine – new clues

AstraZeneca in partnership with the University of Oxford developed one of the first vaccines against COVID. The vaccine, which used an adenovirus to smuggle instructions into human cells to make antibodies against the novel coronavirus, saved countless lives. But a problem soon emerged. A tiny proportion – about one in 50,000 – of those vaccinated developed blood clots.

This blood clot syndrome is known as vaccine-induced immune thrombotic thrombocytopenia (VITT). In people with this condition, something goes wrong with the immune response and people make antibodies that can stick to one of the body’s own proteins.

The protein is called platelet factor 4 (PF4). We know that in the course of infection, many people make antibodies that stick to PF4 as part of the immune response, but these antibodies usually stick weakly. In VITT, antibodies form that can stick to PF4 like superglue.

The antibodies in VITT glue PF4 molecules together, forming large structures known as “immune complexes”. These complexes bind to and activate small cells called platelets that are vital for blood clotting. Normally, platelets float around in the blood in an inactive state, but once activated they spread out, get very sticky, and spew out hundreds of different chemicals.

In VITT, platelets are strongly activated and this causes blood clots. The blood clots commonly affect the veins surrounding the brain, which is a very unusual and rare site for clots. Many people with VITT reported excruciating headaches, which continue to affect survivors.

Billions of platelets get used up in these clots, leading to low numbers of platelets in the blood. In some patients, this led to serious bleeding and nearly one in four died. Many survivors are also have life-long, disabling symptoms.

Looking for clues

In just two and a half years, doctors and scientists around the world have begun to unravel the secrets of VITT. How VITT causes clots and why some people get it is a main area of work. Through understanding this, potential treatments are also being discovered.

So far, there is only one genetic clue as to why some people get VITT. A variation of a gene that makes parts of antibodies is linked to VITT and this is more common in people of European descent – Europeans seem to be at higher risk of VITT. There must be other genes involved, but they are tricky to find. In the UK, scientists have done DNA sequencing on over 200 patients with VITT and results are expected soon.

In our lab, we work on how platelets get activated in VITT. In 2021, our team showed the main mechanism for platelet activation and have recently discovered another mechanism. In a test tube, we can block this activation with commonly used medicines.

Certain genes are linked to greater risk of VITT. Kateryna Kon/ Shutterstock

We also see a lot of variation in how platelets from healthy people respond to PF4 and VITT antibodies. We think that this variation in responses is a reason why some people get VITT. We are doing more work to find out the differences between platelets of “high” and “low” responders.

Another major puzzle with VITT is why so many people have clots in the brain. To put this into perspective, spontaneous clots in the brain are very rare. They only affect around three or four people in a million a year, yet over half of the patients with VITT had these clots.

There are some theories about why clots in the brain happen more in patients with VITT. These include the speed of blood flow, and the stickiness of PF4 and antibodies to the blood vessels. Recently, Canadian scientists showed that patients whose antibodies stick to PF4 the strongest are most likely to get clots in the brain.

Still widely used in low-income countries

Although adenoviral vaccines have saved millions of lives, they have fallen out of favour in developed countries because of the risk of VITT. However, these vaccines are still widely used in low-income countries. They are highly effective, cheap, and much easier to store and transport than mRNA vaccines – such as the Pfizer-BioNTech and Moderna jabs.

Improving the knowledge of VITT has also prompted scientists to look more closely at other patients with unexplained blood clots. Remarkably, more and more patients with clots, low platelets, and VITT-like antibodies are being found. These cases are unrelated to vaccination.

Recently, a VITT-like syndrome was reported in two patients after adenovirus infection rather than vaccination. Testing for these antibodies will probably become routine for patients with unexplained blood clots.

Most importantly, imagine a new pandemic that is a lot more dangerous than COVID – perhaps a third of people who catch it die. There would be panic and chaos. We would desperately need adenoviral vaccines despite the risk of VITT. That’s why it’s important to understand VITT inside and out.

Source：

The Conversation

Published on 30 October, 2023

声明：本站文章版权归原作者及原出处所有。本文章系本站编辑转载，文章内容为原作者个人观点，登载该文章的目的是为了学习交流和研究，并不代表本站赞同其观点和对其真实性负责，本站只提供参考并不构成任何投资及应用建议。

本站是一个学习交流和研究的平台，网站上部分文章为引用或转载，并不用于任何商业目的。我们已经尽可能的对作者和来源进行了告知，但是能力有限或疏忽，造成漏登或其他问题，请及时联系我们，我们将根据著作权人的要求，立即更正或删除有关内容。本站拥有对本声明的最终解释权。