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How Blood Clots: Platelets and the Coagulation Cascade

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

Red blood cells are the most common type of cell in our blood. They pick up oxygen from our lungs and carry it to our tissue cells.

Red blood cells are the most common type of cell in our blood. They pick up oxygen from our lungs and carry it to our tissue cells.

Blood Clotting or Coagulation

Blood clotting or coagulation is a biological process that stops bleeding. It's vital that blood clots when we have a surface injury that breaks blood vessels. Clotting can prevent us from bleeding to death and protect us from the entry of bacteria and viruses. Clots also form inside our body when a blood vessel is injured. Here they prevent blood loss from the circulatory system.

Our body can both make clots and break them down once they've done their job. In most people, a healthy balance is maintained between these two activities. In some people abnormal blood coagulation occurs, however, and their body may not be able to break clots down. A large clot inside a blood vessel is potentially dangerous because it can block blood flow in the vessel. Internal clots that form without an obvious injury or ones that travel through blood vessels are also dangerous.

Coagulation of blood is a fascinating and complex process that involves many steps. Proteins made by the liver and sent into the bloodstream are an essential part of the process. The proteins circulate around the body in our blood, ready for action at any time. An external or internal injury is the trigger that activates the proteins and sets the blood clotting process in motion.

Blood cells and platelets are sometimes referred to as formed elements in blood.

Blood cells and platelets are sometimes referred to as formed elements in blood.

Red blood cells (or erythrocytes) carry oxygen to cells. The five types of white blood cells (leukocytes) fight infections in various ways. Platelets (thrombocytes) are cell fragments that play an essential role in the blood clotting process. They develop a spiky appearance when they're activated.

Hemostasis Steps

Hemostasis is the process in which bleeding is stopped. It involves three steps, which are listed below.

  • Vasoconstriction: narrowing of damaged blood vessels to reduce blood loss. This is caused by contraction of the smooth muscle in the wall of vessels.
  • Activation of platelets: activated platelets stick to each other and to collagen fibres in the broken walls of blood vessels, forming a platelet plug that temporarily blocks blood flow. The platelets also release chemicals that attract other platelets and stimulate further vasoconstriction.
  • Formation of a blood clot: the clot contains fibres that trap the platelets and is stronger and longer-lasting than the platelet plug.

Platelet Activation, Agglutination, and Aggregation

Platelets are small cell fragments in our blood. They have a somewhat irregular form but are roughly disk shaped. They lack a nucleus. Platelets are produced by budding off from a larger cell in bone marrow called a megakaryocyte. They play an important role in the initiation of a blood clot.

The first step in healing a wound is the activation of platelets. When platelets touch the damaged wall of a blood vessel, encounter turbulence in blood flowing around a wound, or encounter specific chemicals in the blood, they become "sticky". They bind to the injured cells in a wound as well as to each other. During this activation process, the platelets become more rounded in shape and develop spikes.

Activated platelets form a mesh, or a platelet plug, that covers and fills a wound. The plug temporarily stops bleeding and is a very helpful emergency response to a wound. It's quite weak, however, and may be removed by flowing blood unless it's strengthened by a blood clot. The activated platelets in a plug release chemicals that are needed by the blood clotting process.

Blood Clotting Summary

A prothrombin activator converts prothrombin into thrombin. Thrombin is an enzyme that converts fibrinogen into fibrin. Prothrombin and fibrinogen are proteins that are always present in our blood.

A prothrombin activator converts prothrombin into thrombin. Thrombin is an enzyme that converts fibrinogen into fibrin. Prothrombin and fibrinogen are proteins that are always present in our blood.

An Overview of the Blood Clotting Process

The blood clotting process is complex and involves many reactions. However, the process can be summarized in three steps.

  • A complex known as a prothrombin activator is produced by a long sequence of chemical reactions.
  • The prothrombin activator converts a blood protein called prothrombin into another protein called thrombin.
  • Thrombin converts a soluble blood protein called fibrinogen into an insoluble protein called fibrin.
  • Fibrin exists as solid fibres which form a tight mesh over the wound. The mesh traps platelets and other blood cells and forms the blood clot.

Prothrombin and fibrinogen are always present in our blood, but they aren't activated until a prothrombin activator is made when we're injured.

The Coagulation Cascade: Blood Clotting in More Detail

Blood clotting occurs in a multi-step process known as the coagulation cascade. The process involves many different proteins. The cascade is a chain reaction in which one step leads to the next. In general, each step produces a new protein which acts as an enzyme, or catalyst, for the next step.

The coagulation cascade is often classified into three pathways—the extrinsic pathway, the intrinsic pathway, and the common pathway.

The extrinsic pathway is triggered by a chemical called tissue factor that is released by damaged cells. This pathway is "extrinsic" because it's initiated by a factor outside the blood vessels. It's also known as the tissue factor pathway.

The intrinsic pathway is triggered by blood coming into contact with collagen fibers in the broken wall of a blood vessel. It's "intrinsic" because it's initiated by a factor inside the blood vessel. It's sometimes called the contact activation pathway.

Both pathways eventually produce a prothrombin activator. The prothrombin activator triggers the common pathway in which prothrombin becomes thrombin followed by the conversion of fibrinogen to fibrin.

Although dividing the coagulation process into extrinsic and intrinsic pathways is a useful approach to the topic and is a widely used tactic, scientists say that it's not completely accurate. For many students of this complex process, however, it's the best solution for understanding blood clotting.

The Classical Blood Coagulation Pathway

A summary of the intrinsic and extrinsic pathways in the coagulation cascade; recent studies have found that additional reactions and clotting factors are involved in the pathways, but this diagram gives a general idea of the process

A summary of the intrinsic and extrinsic pathways in the coagulation cascade; recent studies have found that additional reactions and clotting factors are involved in the pathways, but this diagram gives a general idea of the process

The Roman numerals in a coagulation cascade diagram represent clotting or coagulation factors. These factors are chemicals that are required in the chain of reactions that make up the blood clotting process.

Clotting Factors

The chemicals involved in the coagulation cascade are called clotting or coagulation factors. There are twelve clotting factors, which are numbered with Roman numerals and given a common name as well. The factors are numbered according to the order in which they were discovered and not according to the order in which they react.

Other chemicals are needed for blood clotting in addition to those numbered in the coagulation cascade. For example, vitamin K is an essential chemical in the blood clotting process.

Names and Sources of the Clotting or Coagulation Factors

Coagulation FactorCommon NameSource

Factor l

fibrinogen

liver

Factor ll

prothrombin

liver

Factor lll

tissue factor or thromboplastin

Damaged tissue cells release tissue thromboplastin. Platelets release platelet thromboplastin.

Factor lV

calcium ions

bone, and absorption through the lining of the small intestine

Factor V

proaccelerin or labile factor

liver and platelets

Factor Vl (unassigned)

No longer used

N/A

Factor Vll

proconvertin or stable factor

liver

Factor Vlll

anti-hemophilic factor

platelets and the lining of blood vessels

Factor lX

Christmas factor

liver

Factor X

Stuart Prower factor

liver

Factor Xl

plasma thromboplastin antecedent

liver

Factor Xll

Hageman factor

liver

Factor Xlll

fibrin stabilizing factor

liver

The Factor Vl name is no longer assigned after it was discovered that the chemical that was given the name was actually activated Factor V. The name is traditionally retained in a table of coagulation factors, however.

Studying the Blood Clotting Process

At the high school level, the discussion of blood clotting often begins with the prothombin activator and the previous steps before its formation are ignored or summarized very briefly. At the college or university level, a more detailed knowledge of the process may be needed.

Students sometimes find that studying the coagulation cascade is a challenge, especially when reactions in the cascade must be memorized. Videos from a reliable source can be helpful because they show the blood clotting process visually and can be paused and replayed as necessary. It may be useful to make notes based on a video and then ask an instructor for clarification if necessary. Making frequent diagrams of the cascade can also help a student to memorize the reactions.

Sometimes different sources present slightly different versions of the coagulation cascade. This is due to our lack of precise knowledge of some of the steps or the fact that a published version hasn't been updated with the latest discoveries. If you're studying blood clotting at an educational institution, the version of coagulation that your instructor gives you will be the "official" version.

A Summary of Hemostasis

Anti-Clotting Mechanisms in the Body

Though the ability to coagulate blood is essential, it can be dangerous if it occurs inappropriately. The body has ways to prevent this from happening.

The endothelium is the layer of cells that lines the inside of a blood vessel wall. The smooth surface of the endothelium discourages clot formation when there is no injury. In addition, there is no exposed collagen inside a blood vessel. Collagen is a fibrous protein that provides strength to tissues. When blood contacts collagen, the clotting process is stimulated.

Another factor that prevents unwanted clots from forming is the fact that the clotting proteins in the blood are present in an inactive form. They only become active when the body is wounded.

A chemical called Protein C acts as an anticoagulant by inactivating two of the activated coagulation factors (Factor Va and Factor Vllla). Protein S helps Protein C do its job. The two proteins are very useful for preventing blood clotting.

Stabilization of the fibrin network over a wound by Factor Xlll. Fibrin must be broken down once it's done its job.

Stabilization of the fibrin network over a wound by Factor Xlll. Fibrin must be broken down once it's done its job.

Removing Blood Clots

When a blood clot has served its function and the tissue underneath it has been repaired, the clot needs to be removed. In addition, it's important that any clots inside a blood vessel don't become large enough to block the vessel. Fortunately, the body is able to deal with these problems.

Fibrinolysis is the process in which fibrin is destroyed by an enzyme called plasmin. Plasmin cuts the fibrin threads up into smaller pieces, which can then be further broken up by other enzymes and removed from the body in the urine.

A Blood Clotting Quiz

For each question, choose the best answer. The answer key is below.

  1. What is the name of the protein that forms fibers that trap blood?
    • thrombin
    • prothrombin
    • fibrin
    • fibrinogen
  2. What clotting factor converts fibrinogen into fibrin?
    • Protein C
    • thromboplastin
    • prothrombin
    • thrombin
  3. Which clotting factor appears to be most important in the prothrombin activator complex?
    • Xa
    • Xla
    • Xlla
    • Xllla
  4. How many clotting factors are recognized today?
    • ten
    • eleven
    • twelve
    • thirteen
  5. The most important vitamin for successful blood clotting is:
    • vitamin B12
    • vitamin C
    • vitamin D
    • vitamin K
  6. One of the clotting factors inactivated by Protein C is:
    • Factor lVa
    • Factor VA
    • Factor VllA
    • Factor VlllA
  7. The clotting factor that is no longer used today is:
    • Factor Vl
    • Factor Vll
    • Factor Vlll
    • Factor lX
  8. The extrinsic pathway is triggered by:
    • exposed collagen
    • damaged red blood cells
    • damaged white blood cells
    • tissue factor

Answer Key

  1. fibrin
  2. thrombin
  3. Xa
  4. twelve
  5. vitamin K
  6. Factor VA
  7. Factor Vl
  8. tissue factor

An Impressive and Vital Process

A healthy body protects us by clotting blood when we're injured, removing clots when they're no longer needed, and preventing clots from growing too big. The normal blood clotting process is certainly complicated, but it's also amazing. Learning more about the process may help researchers discover ways to improve coagulation as well as prevent it from occurring inappropriately.

References

Questions & Answers

Question: What are the two targets of positive feedback from the common pathway in blood clotting?

Answer: There are multiple positive feedback reactions involved in coagulation. For example, once thrombin is formed in the common pathway, it stimulates the activation of platelets. It also activates more Factor V and Factor Vlll.

Question: Do white blood cells take part in blood clotting?

Answer: No, white blood cells (or leukocytes) aren’t involved in blood clotting. Instead, they help to protect the body from infection and disease. There are five major types of leukocytes, each with their own characteristics. In order of abundance in our body, these types are neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Multiple types of lymphocytes exist.

White blood cells protect us by a variety of methods. For example, some surround and ingest invading microbes or cellular debris. Others produce proteins called antibodies. Some release other helpful chemicals or activate other leukocytes. The cells play a vital role in our body, even though they don't help blood to clot.

Question: What is the name of the mosquito's anticoagulant, and how does it work?

Answer: Mosquitoes in the subfamily Anophelinae have a peptide called anophelin in their saliva. (The mosquitoes that transmit the malaria parasite belong to this subfamily.) Anophelin inhibits thrombin, preventing blood coagulation. Mosquitoes in the subfamily Culicinae have an anticoagulant in their saliva that inhibits the coagulation or clotting factor known as FXa. It’s referred to as an “FXa-directed anticoagulant”.

The saliva of mosquitoes isn’t well characterized. It may contain additional chemicals that affect blood clotting and make obtaining the liquid more efficient. Only female mosquitoes feed on the liquid. They need blood proteins in order to make their eggs.

Question: What is the final substance of a blood clot?

Answer: A blood clot consists of a mesh of fibrin threads, clumped platelets, and trapped red blood cells. Fibrin is a protein made by the coagulation cascade.

Question: Are prothrombin and fibrinogen types of white blood cells?

Answer: No, prothrombin and fibrinogen are proteins, not cells. More specifically, they are glycoproteins—proteins with attached carbohydrate. They are both found in blood plasma.

Question: What role does vitamin K play in clotting ?

Answer: Vitamin K is essential for the blood clotting process because it’s required for the action of clotting or coagulation factors ll (prothrombin), Vll, IX, and X. It’s also required for the action of the anticoagulation proteins C, S, and Z.

Question: Is prothrombin a coagulation factor?

Answer: Yes, as I show in the table, prothrombin is also known as coagulation factor ll (the Roman numeral for 2). It's converted into thrombin, which in turn converts fibrinogen into fibrin.

Question: What are two mechanisms by which blood clots are prevented from propagating back through the circulatory system from a wound?

Answer: Once a blood clot has formed to stop bleeding and the wound has healed sufficiently, the body breaks the clot down. In some cases, however, the clot leaves the wounded area and travels through the bloodstream. The body normally prevents this from happening.

The clot contains an enzyme called plasmin. The enzyme enters the clot as plasminogen, an inactive enzyme made by the liver and transported in the blood. The lining of the damaged vessels in the clot slowly releases tissue plasminogen activator. This changes plasminogen into plasmin, which breaks down the fibrin in the clot in a process known as fibrinolysis. Urokinase plasminogen activator and some additional chemicals also activate plasminogen.

Question: Is thromboplastin involved in blood clotting?

Answer: Yes, as shown in the table in the article and the picture illustrating a summary of hemostasis, thromboplastin is involved in blood clotting. It's an important factor in the process.

Question: What is the role of factor Xlll?

Answer: Factor Xlll is also known as fibrin stabilizing factor. It helps fibrin strands to connect to each another. Though the blood clot may form without Factor XIII, it soon breaks down, leading to bleeding.

Question: What stops the positive feedbacks in the coagulation process from clotting all the blood in our body?

Answer: Positive feedback causes an action to repeat and to be amplified until the condition that caused the feedback no longer exists. At this point, the feedback stops. For example, a wound in the lining of a blood vessel stimulates positive feedback via specific processes until the wound is repaired and no longer exists. In at least some cases of positive feedback, a chemical antagonist is involved in stopping the feedback.

© 2013 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on July 16, 2019:

I'm glad the information helped you.

Linda Crampton (author) from British Columbia, Canada on July 16, 2019:

Hi. If you look at the first half of the article you'll see an overview and summary of the blood clotting process that describes the basic steps. The second half of the article contains more details.

Annete on July 13, 2019:

The above information is important and helpful to me.

Ma on July 13, 2019:

I want the simple blood clotting process in an ordinary way

Linda Crampton (author) from British Columbia, Canada on February 11, 2019:

Thank you very much for such a kind comment! I appreciate the fact that you’ve shared the article, too.

Boo Soon Yew from Penang, Malaysia on February 11, 2019:

TQ so much Linda for such an informative & comprehensive article on Blood Clotting Mechanism which transcends not just High School Biology, but also Pre-U and even Uni level Cell Biology or Biochemistry !!

I found your article after my student asked me a probing question, "Is thrombin an enzyme ?"

I answered it should be since it breaks up fibrinogen to fibrin, but I needed to confirm as we were never outright told at high school level that it is an enzyme. I did remark that they (prothrombin, thrombin, fibrinogen & fibrin) are all proteins.

But your article puts everything to rest !! I am sharing this on my Facebook and tagging my students. :)

Linda Crampton (author) from British Columbia, Canada on June 13, 2018:

Factor V is encoded by the F5 gene. It’s produced in an inactive form and enters the plasma. Factor Vlll is encoded by the F8 gene, produced in an inactive form, and then sent into the plasma. Both factors are changed into their active form by thrombin. Researchers have found that they can also be activated by active Factor X. They may be activated by other substances as well. Research is ongoing.

Tharindu on June 08, 2018:

How acitivate factor v and activate factor viii are formed before forming thrombin

Linda Crampton (author) from British Columbia, Canada on March 22, 2018:

I'm sorry about your mother's situation, Jaishree. I hope she recovers well from her problems. I can't speculate about what may be wrong with her blood because I'm a science writer, not a health professional. Doctors that are familiar with your mother's medical condition need to answer your question.

Jaishree on March 22, 2018:

Hello Linda, my Mom recently did heart surgery but has had two incidences of bleeding and clotting around her heart. The surgeons went back in, removed the clots and dried up the blood but we are worried that this may occur again as it has already happened twice. They now suspect that something may be wrong with her blood. Can you offer some insight as to what may be wrong? Thanks for your urgent reply.

Linda Crampton (author) from British Columbia, Canada on February 23, 2018:

Thank you very much, Mages.

Mages on February 23, 2018:

Thank you for simplifying it.

Sharing the link to the students

Linda Crampton (author) from British Columbia, Canada on January 21, 2018:

Hi, Ram. Platelet donations are used in the treatment of some diseases, so in this sense people can use platelets that come from an external source, or another person.

Ram on January 21, 2018:

Can we use external platelets?

Linda Crampton (author) from British Columbia, Canada on January 06, 2018:

Thank you very much, Daniel.

Daniel A. on January 06, 2018:

Thank you so much!! God bless you!!

Linda Crampton (author) from British Columbia, Canada on December 05, 2017:

You're welcome, Alreem.

Alreem on December 05, 2017:

Thank you so much ....

Linda Crampton (author) from British Columbia, Canada on August 23, 2017:

Thank you, Daniel.

DANIEL LOKA on August 20, 2017:

its a wonderful explanation with summerized notes

thanka very much

Linda Crampton (author) from British Columbia, Canada on July 27, 2017:

Thank you very much for the comment, Fahana.

Fahana on July 27, 2017:

Very easy to understand that blood clotting procedure!!! Thank you so much.

Linda Crampton (author) from British Columbia, Canada on July 24, 2017:

Hi, Shannon. I don't know of any specific sites, but when I searched for "concentration of thrombin needed for hemostasis" I found some websites with numerical data that may be helpful for you.

Shannon on July 24, 2017:

Hi, I found this really informative.

Im trying to find out more about thrombin, and if there is an optimal concentration to achieve haemostasis. I am currently comparing some products that are widely used in surgery. Are there any sites that you could direct me to?

Regards,

Linda Crampton (author) from British Columbia, Canada on June 20, 2017:

Thank you very much.

the best on June 20, 2017:

amazing explanation

Linda Crampton (author) from British Columbia, Canada on November 22, 2016:

Thank you very much for the kind comment, mariya.

mariya on November 22, 2016:

most helpful article ever! thankyou so much!!

Linda Crampton (author) from British Columbia, Canada on October 29, 2016:

Thanks, hania. I appreciate your comment.

hania on October 29, 2016:

your explanation is fantastic thanks alot

Linda Crampton (author) from British Columbia, Canada on August 01, 2016:

Thank you very much for the comment, Vellur. I appreciate your visit and vote.

Nithya Venkat from Dubai on August 01, 2016:

Blood clotting is an amazing process and you have explained it so clearly. Interesting and informative article, voted up.

Linda Crampton (author) from British Columbia, Canada on January 20, 2015:

Thank you very much, mehwish.

mehwish on January 20, 2015:

Very easy way for understsnding blood clotting...

Thanks

Linda Crampton (author) from British Columbia, Canada on January 13, 2015:

Thank you, charity sekyi. I'm glad the article was helpful for you.

charity sekyi on January 13, 2015:

It has help me to know much for what am looking for

Linda Crampton (author) from British Columbia, Canada on February 21, 2014:

Thank you very much for the comment, Porschia.

Porschia on February 21, 2014:

great information

Linda Crampton (author) from British Columbia, Canada on March 14, 2013:

Thank you very much, Sheri Faye!

Sheri Dusseault from Chemainus. BC, Canada on March 14, 2013:

Now that was interesting and well written! Thank you!

Linda Crampton (author) from British Columbia, Canada on March 13, 2013:

Thank you very much for the visit and the comment, ryanjhoe!

ryanjhoe from Somewhere over the rainbow on March 13, 2013:

This article is very helpful for me to get the information about blood clot and I never really understand about it before. Thanks for sharing this!

Linda Crampton (author) from British Columbia, Canada on March 05, 2013:

Thank you very much for the comment, Dianna. I appreciate your visit, as always!

Dianna Mendez on March 05, 2013:

Your posts are always a great read. Again, your detailed photos, charts and research makes an excellent article. Thanks for the interesting education of blood clots.

Linda Crampton (author) from British Columbia, Canada on February 25, 2013:

Thank you very much, drbj! I appreciate the comment!!

drbj and sherry from south Florida on February 25, 2013:

Your explanation of blood clotting is so detailed and complete, Alicia, you might want to re-title your hub: "Everything in the World You Would Ever Want to Know and Then Some About Blood Clotting." :)

Linda Crampton (author) from British Columbia, Canada on February 24, 2013:

Thanks for the visit and the comment, Deb. Our bodies are definitely amazing!

Deb Hirt from Stillwater, OK on February 24, 2013:

Our body really does do a lot of amazing things. Thanks for the great explanation on clotting.

Linda Crampton (author) from British Columbia, Canada on February 24, 2013:

Thank you very much for the comment, Vicki. I think the problem with the quiz appearing is probably because you were using an iPad to read the hub. I'll have to see if the quiz appears on my iPad!

Vickiw on February 24, 2013:

Hi Alicia, a really interesting Hub, made very understandable and user friendly with your diagrams and pictures. Quality. Couldn't get your quiz though, maybe because I am on myiPad ?

Linda Crampton (author) from British Columbia, Canada on February 24, 2013:

Thank you so much for the lovely comment, Austinstar. I hope that zombie apocalypse never arrives!

Lela from Somewhere near the heart of Texas on February 24, 2013:

You could definitely write technical books for medical students and nurses! Great job!

We need to save your hubs in case of the zombie apocalypse.

Linda Crampton (author) from British Columbia, Canada on February 23, 2013:

Thank you, Bill. I appreciate the comment very much!

Bill Holland from Olympia, WA on February 23, 2013:

You do such a great job with these medical hubs. They are so detailed and yet you make them easy to understand. Great job and thank you for the information.