How Blood Clots: Platelets and the Coagulation Cascade

Updated on June 27, 2017
AliciaC profile image

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. | Source

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.

From left to right, a red blood cell, an activated platelet and a white blood cell
From left to right, a red blood cell, an activated platelet and a white blood cell | Source

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) play an essential role in the blood clotting process. They develop a spiky appearance when they're activated.

Hemostasis

Hemostasis is the process in which bleeding is stopped. It involves three steps.

  • 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.

The Process of Platelet Activation

Platelet Agglutination, Activation, and Aggregation

Platelets are small cell fragments in our blood. They have a somewhat irregular form but are roughly disk shaped. They are produced by budding off from a larger cell in bone marrow called a megakaryocyte. Platelets 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. | Source

Summary 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.

Blood Clotting Overview

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 | Source

Clotting or Coagulation Factors

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.

Hemostasis Mechanism

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 Factor
Common Name
Source
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.

Coagulation Cascade Animation

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 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 the Hemostasis Process

A summary of the blood clotting process
A summary of the blood clotting process | Source

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. | Source

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 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.

A Blood Clotting Quiz

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References

  • Overview of Hemostasis from the Merck Manual
  • Gale, A. J. (2011). Current Understanding of Hemostasis. Toxicologic Pathology, 39(1), 273–280. http://doi.org/10.1177/0192623310389474
  • Palta, S., Saroa, R., & Palta, A. (2014). Overview of the coagulation system. Indian Journal of Anaesthesia, 58(5), 515–523. http://doi.org/10.4103/0019-5049.144643

Questions & Answers

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

    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.

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

    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.

  • Do white blood cells take part in blood clotting?

    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.

  • Is thromboplastin involved in blood clotting?

    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.

© 2013 Linda Crampton

Comments

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    • AliciaC profile imageAUTHOR

      Linda Crampton 

      4 months ago from British Columbia, Canada

      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.

    • profile image

      Tharindu 

      4 months ago

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

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      6 months ago from British Columbia, Canada

      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.

    • profile image

      Jaishree 

      6 months ago

      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.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      7 months ago from British Columbia, Canada

      Thank you very much, Mages.

    • profile image

      Mages 

      7 months ago

      Thank you for simplifying it.

      Sharing the link to the students

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      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.

    • profile image

      Ram 

      8 months ago

      Can we use external platelets?

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      9 months ago from British Columbia, Canada

      Thank you very much, Daniel.

    • profile image

      Daniel A. 

      9 months ago

      Thank you so much!! God bless you!!

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      10 months ago from British Columbia, Canada

      You're welcome, Alreem.

    • profile image

      Alreem 

      10 months ago

      Thank you so much ....

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      13 months ago from British Columbia, Canada

      Thank you, Daniel.

    • profile image

      DANIEL LOKA 

      14 months ago

      its a wonderful explanation with summerized notes

      thanka very much

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      14 months ago from British Columbia, Canada

      Thank you very much for the comment, Fahana.

    • profile image

      Fahana 

      14 months ago

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

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      14 months ago from British Columbia, Canada

      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.

    • profile image

      Shannon 

      14 months ago

      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,

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      16 months ago from British Columbia, Canada

      Thank you very much.

    • profile image

      the best 

      16 months ago

      amazing explanation

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      23 months ago from British Columbia, Canada

      Thank you very much for the kind comment, mariya.

    • profile image

      mariya 

      23 months ago

      most helpful article ever! thankyou so much!!

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      23 months ago from British Columbia, Canada

      Thanks, hania. I appreciate your comment.

    • profile image

      hania 

      23 months ago

      your explanation is fantastic thanks alot

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      2 years ago from British Columbia, Canada

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

    • Vellur profile image

      Nithya Venkat 

      2 years ago from Dubai

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

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      3 years ago from British Columbia, Canada

      Thank you very much, mehwish.

    • profile image

      mehwish 

      3 years ago

      Very easy way for understsnding blood clotting...

      Thanks

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      3 years ago from British Columbia, Canada

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

    • profile image

      charity sekyi 

      3 years ago

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

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      4 years ago from British Columbia, Canada

      Thank you very much for the comment, Porschia.

    • profile image

      Porschia 

      4 years ago

      great information

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

      Thank you very much, Sheri Faye!

    • Sheri Faye profile image

      Sheri Dusseault 

      5 years ago from Chemainus. BC, Canada

      Now that was interesting and well written! Thank you!

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

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

    • ryanjhoe profile image

      ryanjhoe 

      5 years ago from Somewhere over the rainbow

      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!

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

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

    • teaches12345 profile image

      Dianna Mendez 

      5 years ago

      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.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

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

    • drbj profile image

      drbj and sherry 

      5 years ago from south Florida

      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." :)

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

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

    • aviannovice profile image

      Deb Hirt 

      5 years ago from Stillwater, OK

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

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

      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!

    • profile image

      Vickiw 

      5 years ago

      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 ?

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

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

    • Austinstar profile image

      Lela 

      5 years ago from Somewhere near the center of Texas

      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.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      5 years ago from British Columbia, Canada

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

    • billybuc profile image

      Bill Holland 

      5 years ago from Olympia, WA

      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.

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