How Blood Clots: Platelets and the Coagulation Cascade
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.
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 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
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
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.
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
tissue factor or thromboplastin
Damaged tissue cells release tissue thromboplastin. Platelets release platelet thromboplastin.
bone, and absorption through the lining of the small intestine
proaccelerin or labile factor
liver and platelets
Factor Vl (unassigned)
No longer used
proconvertin or stable factor
platelets and the lining of blood vessels
Stuart Prower factor
plasma thromboplastin antecedent
fibrin stabilizing factor
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
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.
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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- 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
© 2013 Linda Crampton