Whenever there is bleeding the body responds by forming a blood clot to stop the bleed and maintain hemostasis. In medical terminology hemostasis means to stop (-stasis) bleeding (hemo-).
HEMOSTASIS
Hemostasis is achieved in 2 broad stages: primary hemostasis and secondary hemostasis.
Secondary hemostasis is the activation of the coagulation cascade.
Each pathways consist of multiple clotting factors that activate each other in sequence.
The intrinsic pathway is activated in response to factors in the blood, while the extrinsic pathway is activated by tissue factors.
Activation of either or both pathways will lead to activation of the common pathway.
Inactive factors are represented by roman numerals. When they are activated they are noted with an “a” after the roman numeral. E.g. factor ten when inactive will be written as X. When activated it will be written as Xa.
Primary Hemostasis
Primary hemostasis occurs rapidly to create a “platelet plug” in an attempt to immediately stop bleeding. This plug consists of platelets aggregating at the site of injury to a blood vessel.
The von Willebrand factor (vWF) helps platelets attach to the vessel wall. This plug is very loose.
Secondary Hemostasis
Secondary hemostasis (aka coagulation cascade) has to be activated. The end result of the coagulation cascade is a more stable clot. This allows the body time to heal injury to the vessel without bleeding out.
The coagulation cascade (secondary hemostasis) stabilizes the platelet plug via generation of fibrin crosslinks that embeds into the clot.
Three pathways make up the coagulation cascade: (1) extrinsic pathway and (2) intrinsic pathway that lead into the (3) common pathway.
Watch on YouTube
Vitamin K & Calcium
Calcium ions play a significant role throughout the coagulation cascade. They are responsible for the complete activation of several clotting factors as well as platelet activation.
Vitamin K also plays a significant role throughout the coagulation cascade because it is required for the synthesis of some clotting factors. See Warfarin: The Fundamentals for in depth notes.
Clotting factors dependent on both vitamin K and calcium: (II) 2, (VII) 7, (IX) 9, (X) 10
Natural anticoagulants that dependent on vitamin K only: Protein C + S
Now let’s look at each pathway individually before bringing it all together.
Subscribe for Access to Exclusive Content
Extrinsic Pathway
Trigger: external trauma and tissue factor
Factors: VII (7) and III (3). Factor III is most commonly referred to as tissue factor.
Tissue factor (TF) is a membrane protein that is separated from blood by the vascular endothelium (the inner lining of arteries, veins and capillaries). In a “healthy” patient TF never makes contact with blood.
When the body receives an injury sufficient to cause damage to the endothelial lining, this will cause TF to come into contact with and activate factor VII (7) in the blood.
Factor VII (7), TF and calcium form a complex that activates the common pathway of the coagulation cascade via factor X (10).
Tissue factor has what is referred to as a non-uniform distribution throughout the body. There are high levels in organs like the brain, lungs and placenta and low levels in organs like the spleen and liver.
Intrinsic Pathway
Trigger: collagen in the presence of high molecular weight kininogen.
Factors: XII (12), XI (11), IX (9) and VIII (8) and II (thrombin)
Collagen is found in the subendothelial layer below the inner lining of blood vessels. In a healthy patient there is no contact between this subendothelial collagen and blood.
When there is vascular injury subendothelial collagen becomes exposed to blood. High molecular weight kininogens, found in blood, acts as a cofactor in the presence of collagen to initiate the intrinsic pathway via factor XII (12). Factor XII (12) then activates factor XI (11), which activates factor IX (9).
In response to injury small amounts of thrombin in the blood converts inactive factor VIII(8) to its active form.
The intrinsic pathway terminates into the common pathway when factor VIII, factor IX and calcium form a complex that then activates factor X in the common pathway.
Common Pathway
Trigger: activation of intrinsic and/or extrinsic pathways
Factors: X (10), V (5), II (2), I (1), XIII (13)
The common pathway begins with the activation of factor X to Xa by either or both the intrinsic and extrinsic pathway. It culminates in the production of a stabilizing fibrin complex.
- Factor Xa activates factor II to IIa (better known as thrombin).
- Factor V (5) forms a complex with thrombin to activate factor I to Ia (better know as fibrinogen).
- Factor XIII (13) forms a complex with calcium which leads to the final step of converting fibrinogen to fibrin crosslink.
These crosslink will then strengthen and stabilize the lose platelet plug formed during primary hemostasis allowing more time for the injured tissue to heal.
What Stops the Coagulation Cascade
The coagulation cascade is self perpetuating, factors activate each other in sequence. If this cascade went unchecked we would have excessive thrombosis (clot formation).
The natural anticoagulants protein C and protein S limit the coagulation cascade, preventing excessive clotting.
Protein S is a cofactor for the conversion of protein C to its active form APC (activated protein C). APC is a protease that inhibits activated factor V (Va) and activated factor VIII (VIIIa).
When thrombin binds to the endothelial cells at the site of injury this initiates the activation of protein C and S.
This will prevent further activation of thrombin and the conversion of fibrinogen to fibrin in the coagulation cascade thus limiting clot formation.
This video will help you to visualize and reinforce everything you’ve read in this study unit.
I hope this study unit has provided clarification on what can be a complex topic. If this unit has been helpful I would love to hear from you! Leave a question or comment below.
Subscribe
Subscribe to get the latest study unit in your inbox.
The information on this website is intended to be used solely for educational and informational purposes. While the content may be about specific medical and health care issues, it is not a substitute for or replacement of personalized medical advice and is not intended to be used as the sole basis for making individualized medical or health-related decisions.
6 thoughts on “What You Need to Know: Hemostasis”