Blood clot discovery

BBC News has reported that scientists have found a potential way to prevent blood clots that can cause heart attacks. It said that existing anti-clotting medicines reduce the risk of heart attack, but can also cause dangerous bleeding in some people. The BBC said the results, from a study in mice, could be used to develop better treatments.

By removing a specific protein, PKCα, from the platelet blood cells involved in clotting, dangerous blood clots don’t develop.

This animal study has shown that PKCα has a crucial role in clot formation. In particular, it found the absence of PKCα stops platelets sticking to each other in a mass, but doesn’t affect the responses that may be important for normal wound healing.

This is early research, and it is important not to make too many assumptions as to how humans may benefit from this. While these findings will be of interest to scientists, any clinical application is still some time in the future.

Where did the story come from?

Dr Olga Konopatskaya and colleagues from the University of Bristol, the University of Maastricht, the University of Birmingham and other academic institutions in the US carried out this study. The research was funded by grants from the British Heart Foundation, the Medical Research Council and the NIH. The study was published in the (peer-reviewed) medical journal: The Journal of Clinical Investigation.

What kind of scientific study was this?

This laboratory study in mice aimed to investigate the role of different forms of the protein family PKC (protein kinase C) in the formation of blood clots, particularly how PKC affects the behaviour of platelets, which play an important role in the formation of blood clots. Platelets are irregularly shaped blood cells that clump together to block blood flow in response to injury, thereby starting off the healing process.

There are several forms of PKC (α, β, δ, θ) also known as alpha, beta, delta and theta, and the researchers wanted to see what role they played in clot formation. They say that PKCα has been shown to have a role in a variety of cellular functions, including cell growth, differentiation, movement and adhesion, as well as regulation of tumour progression.

The researchers genetically engineered mice to lack the gene needed for them to make PKCα. These mice were still able to make the other forms of PKC (β, δ, θ). Blood from the mice was then used in a series of laboratory experiments, investigating how the blood behaved when passed over a collagen surface (i.e. whether the platelets stuck to it) and how the platelets responded to each other (whether they clumped). The methods used were complex as the researchers were investigating the role that PKCα plays in reactions at a cellular level.

The researchers confirmed their findings in live mice, some of which had been genetically engineered to lack PKCα. They induced an injury in a muscle in the animals’ abdomen and observed how the blood responded to the injury (through a type of microscopy enabling them to view the living tissue outside of the bodies of the mice). They also assessed whether normal response to injury was affected, by comparing how long it took blood to stop flowing from a tail injury in normal mice and the mice that couldn’t produce PKCα.

What were the results of the study?

The researchers found that blood from mice that did not produce PKCα had the same ability to adhere to a collagen or fibrinogen coated surfaces as normal mouse blood, but was less likely to aggregate together to form clumps that may ultimately lead to blood clots.

The researchers explained that this seemed to be because PKCα is involved in the cellular pathways that turn on the ability of the platelets to attract each other, and its absence meant less of an attraction (one mechanism was through reducing secretions that encourage aggregation).

What interpretations did the researchers draw from these results?

The researchers suggest that their studies reveal that PKCα may be a good target for antithrombotic treatments (drugs to prevent blood clots). They say that targeting this particular form of PKC protein would affect the formation of dangerous blood clots, but not affect the other important adhesive functions of the platelets, which is the first step in wound healing.

What does the NHS Knowledge Service make of this study?

This animal study has investigated in more detail the role that PKC proteins play in the formation of dangerous blood clots and in normal healing of wounds. There are several points to raise:

• This study was in mice and the relevance of its findings to humans is not clear. It is not possible to conclude from this study that humans would respond in the same way to a lack of PKCα.
• If the findings are confirmed in humans, it would still be some time before drugs are developed that can selectively target the activity of PKCα and prevent dangerous thrombus formation.
• This study was small. The in vivo (i.e. live mice) parts seem to have only included two mice (one genetically engineered mouse and one normal mouse). Conclusions based on larger numbers of animals would be more robust.

Overall, the results of this study will be of interest to scientists. More research is expected on the role of PKC proteins in clot formation in humans and whether PKCα in particular can be a target of therapies to reduce the formation of internal blood clots.