What Is the Main Idea?

A stroke happens when the blood supply to part of the brain is cut off or reduced and can be life-threatening. In the open-access article “Clinical Significance of Plasma D-Dimer and Fibrinogen in Outcomes after Stroke: A Systematic Review and Meta-Analysis”, published in the journal Cerebrovascular Diseases, the authors investigate whether there is a relationship between the levels of D-dimer and fibrinogen in blood samples given by people who have experienced stroke and their outcomes.

What Else Can You Learn?

In this blog post, the symptoms and causes of stroke are described. The process of blood clotting and biomarkers are also discussed.

What Is Stroke?

A stroke is a serious medical emergency that can be life-threatening. The oxygen and nutrients that brain cells need to function properly are carried around the brain by the blood. A stroke happens when the blood supply to part of the brain is cut off or reduced, and the brain cells can no longer get all the oxygen and nutrients they need. They quickly begin to die (within minutes), which can cause brain damage and other complications.

There are two types of stroke:

  • Ischemic strokes are the most common (around 85% are this type) and are caused when blockages in blood vessels cut off or reduce the blood supply to part of the brain. The blockages may either develop in the blood vessels inside the brain or develop elsewhere in the body and travel to the brain via the bloodstream.
  • Hemorrhagic strokes are less common (around 15% are this type) and are caused by a blood vessel that supplies blood to the brain rupturing, causing bleeding in or around the brain. As well as causing brain cells to die, the bleeding causes irritation and swelling, and pressure can build up in surrounding tissues. This can lead to more brain damage.

As well as the two types of stroke described above, some people experience “mini-strokes” called transient ischemic attacks (TIAs). A TIA is essentially a stroke caused by a temporary, short-term blockage, so the symptoms do not last long. Once the blockage clears the symptoms stop. Although someone who has a TIA may feel better quickly they still need medical attention as soon as possible, because the TIA may be a warning sign that they will have a full stroke in the near future.

What Are the Symptoms of Stroke?

If someone is having a stroke they need urgent treatment. Don’t hesitate to call for medical help. The quicker they receive treatment the less brain damage is likely to occur. The main symptoms of stroke can be remembered using the word “FAST”.

  • Face: The person may be unable to smile, or one side of their face or their mouth may have dropped.
  • Arms: The person may not be able to lift both arms and keep them there.
  • Speech: The person may not be able to talk or their speech may be slurred; they may also have difficulty understanding what you are saying.
  • Time: Call for medical help immediately if the person has any of these signs or symptoms.

Other symptoms of stroke include sudden severe headache, weakness or numbness on one side of the body, confusion or memory loss, dizziness or a sudden fall, and/or blurred vision or loss of sight (in one or both eyes).

What Are the Effects and Outcomes of Stroke?

The effects of stroke vary from one person to another and depend on the type of stroke, its severity, whether this is the first stroke they’ve experienced, and which part of the brain is affected. Different parts of the brain have different functions, so the effects of stroke in the part of the brain that controls movement and speech can be very different to those in the part that controls breathing and heart functions. Predicting the outcomes of stroke is difficult. Although some people who survive a stroke recover well, others can be left with disabling problems that they never recover from. These can include physical and communication problems; extreme tiredness and fatigue; emotional, behavior, and memory changes; and thinking problems. Many factors are associated with the outcomes of people who have a stroke, including age, sex, the severity of the stroke, and whether or not they have other conditions such as atrial fibrillation or diabetes. It is hoped that the development of new ways to predict stroke outcomes can help to improve the outcomes of patients and maximise their recovery.

How Can We Predict the Outcomes of Stroke?

Studies have shown that the combination of a number of biomarkers could improve the accuracy of predicting the outcomes of stroke. Biomarkers are measurable characteristics, such as molecules in your blood or changes in your genes, that indicate what is going on in the body. They can indicate that your body is working normally, the development or progress of a disease or condition, or the effects of a treatment. Because ischemic stroke is caused by blockages in blood vessels, components of the system that regulates the process of blood clotting may be useful in stroke outcome prediction.

How Does the Blood Clotting System Work?

The blood clotting system (known as the “coagulation” system) plays an essential role in the body’s ability to heal. The system is activated when the lining of a blood vessel is damaged and regulates the process by which liquid blood changes to a gel, forming a blood clot, which stops the bleeding and starts the repair process. The process by which blood clots are formed involves a number of proteins and platelets (a type of blood cell). When a blood vessel is damaged, platelets cluster at the site of damage and bind together to seal it. The platelets have receptors on their surfaces that bind a molecule called thrombin, which converts a soluble protein called fibrinogen into a different form called fibrin. Fibrin can form long, tough, insoluble strands that bind to the platelets and cross-link together to form a mesh on top of the platelet plug. Lots of different molecules are involved in this process, but platelets and fibrin are major players.

While it is important that blood can clot when needed, it is also essential that the process is regulated so that unnecessary blood clots can be broken down. Plasminogen plays an important role in this. It circulates in the blood stream in a “closed” (inactive) form. When it binds to a blood clot it opens up, enabling enzymes to cleave (split) it to form a protein called plasmin. Plasmin is able to dissolve fibrin blood clots by cleaving fibrin and many other proteins found in blood plasma (the liquid component of blood that remains when all the blood cells are removed). One of the products when plasmin breaks down fibrin is called D-dimer, which is often measured in blood samples because it indicates whether or not the blood clotting system has been activated. Increased levels of D-dimer and fibrinogen in blood plasma have been reported to be linked to damage to the blood–brain barrier (this regulates the molecules in the blood that can enter the central nervous system).

What Did This Study Show?

The authors investigated whether or not levels of D-dimer and indicators of fibrin breakdown in the blood are associated with stroke outcomes by conducting a meta-analysis. A meta-analysis is a type of research study that statistically analyses the results of a number of studies that have been conducted independently but that have looked at the same research question. In this study, the authors analysed 52 studies that included 21,473 patients who had had a stroke. The results showed that high D-dimer and fibrinogen levels in blood samples given by the patients were significantly associated with poor outcomes such as death after stroke, having another stroke, and early neurologic degeneration (caused by cells in the nervous system stopping working or dying, affecting many of the body’s activities). This indicates that plasma D-dimer and fibrin levels could be used to screen patients for the likelihood of adverse outcomes after stroke, to identify patients at higher risk of poor outcomes so that they can benefit from close monitoring and potentially also preventive treatment. The authors hope that combining D-dimer and fibrin as biomarkers in clinical follow-up after stroke may help to improve the effectiveness of treatment strategies after stroke and enable them to be tailored to meet the needs of individual patients.

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