s1
s2
s3
s4
g1
g2
g3
g4
g5
g6
g7
g8
XII
XI
IX
VIIa
VIII
vW
X
Va
IIa
Ia
XIIIa
CLOT
Coagulation Cascade
The coagulation cascade is a part of secondary hemostasis. The cascade includes an intrinsic pathway and extrinsic pathway which both lead to the common pathway to fibrin formation. The coagulation cascade works like a series of gears—each coagulation factor must activate the next until the clot is formed. If any factor is missing from the coagulation cascade, the clot won’t form correctly.
Condition: Hemophilia A, No Inhibitors
Hemophilia A is a bleeding disorder caused by a missing or defective factor VIII clotting protein. Without enough working factor VIII, a strong clot cannot form. People with hemophilia A bleed longer than others and can have bleeds in their joints, muscles, or skin.
Condition: Hemophilia A
Treatment: Replacement Factor VIII
People with hemophilia A can infuse replacement factor VIII into their vein or a port when they have a bleed. By infusing factor VIII, the body can now use it in the intrinsic pathway to form a strong, durable clot.
Condition: Hemophilia A, Low-titer Inhibitors
Some people with hemophilia A can have an allergic reaction to their replacement factor. Their immune system thinks that the replacement factor is a foreign substance and releases antibodies (inhibitors) that inactivate replacement factor VIII.
Condition: Hemophilia A, Low-titer Inhibitors
Treatment: High Replacement Factor VIII
If your body has a weak immune reaction to replacement factor, it only releases low amounts of antibodies or inhibitors, called low-titer inhibitors. If you infuse a high amount of replacement factor VIII when you have a bleed, the antibodies only bind to some of the replacement factor. The rest of replacement factor VIII can be used in the intrinsic pathway to help form a strong, durable clot.
Condition: Hemophilia A, High-titer Inhibitors
If your body has a strong immune reaction to replacement factor, it releases a lot of antibodies or inhibitors, called high-titer inhibitors. When antibodies or inhibitors bind to replacement factor VIII, the replacement factor will no longer work in your body the way it should. You may need to use bypassing agents instead when you have a bleed.
Condition: Hemophilia A, High-titer Inhibitors
Treatment: aPCC
Activated prothrombin complex concentrate (aPCC) is one of two bypassing agents approved to treat bleeds in someone with a high-titer inhibitor. aPCC contains several different clotting factors in the coagulation cascade, bypassing the need for factor VIII. When you treat a bleed with aPCC, these other factors activate the common pathway and lead to thrombin production, which then helps your body to form a strong, durable clot.
Condition: Hemophilia A, High-titer Inhibitors
Treatment: FVIIa
Activated factor VII (FVIIa) is one of two bypassing agents approved to treat bleeds in someone with a high-titer inhibitor. By using FVIIa to treat a bleed, the body can “bypass” the intrinsic pathway to clot formation, eliminating the need for FVIII. FVIIa uses the extrinsic pathway to activate factor X and start the common pathway to a thrombin burst, leading to the formation of a strong, durable clot.
Condition: Hemophilia B, No Inhibitors
Hemophilia B is a bleeding disorder caused by a missing or defective factor IX clotting protein. People with hemophilia B bleed longer than others and can have bleeds in their joints, muscles, or their skin. Hemophilia B is four times less common than hemophilia A.
Condition: Hemophilia B
Treatment: Replacement Factor IX
People with hemophilia B can infuse replacement factor IX into their vein or a port when they have a bleed. By infusing factor IX, the body can now use it in the intrinsic pathway to form a strong, durable clot.
Condition: Hemophilia B, Low-titer inhibitors
Some people with hemophilia B can have an allergic reaction to their replacement factor. Their immune system thinks that the replacement factor is a foreign substance and releases antibodies (inhibitors) that inactivate replacement factor IX.
Condition: Hemophilia B, Low-titer inhibitors
Treatment: High Replacement Factor IX
If your body has a weak immune reaction to replacement factor, it only releases low amounts of antibodies or inhibitors, called low-titer inhibitors. If you infuse a high amount of replacement factor IX when you have a bleed, the antibodies only bind to some of the replacement factor. The rest of the replacement factor IX can be used in the intrinsic pathway to help form a strong, durable clot.
Condition: Hemophilia B, High-titer inhibitors
If your body has a strong immune reaction to replacement factor, it releases a lot of antibodies or inhibitors, called high-titer inhibitors. When antibodies or inhibitors bind to replacement factor IX, the replacement factor will no longer work in the body the way it should. You may need to use bypassing agents instead when you have a bleed.
Condition: Hemophilia B, High-titer inhibitors
Treatment: aPCC
Activated prothrombin complex concentrate (aPCC) is one of two bypassing agents approved to treat bleeds in someone with a high-titer inhibitor. aPCC contains several different clotting factors in the coagulation cascade, bypassing the need for Factor IX. When you treat a bleed with aPCC, these other factors activate the common pathway and lead to thrombin production, which then helps your body to form a strong, durable clot.
Condition: Hemophilia B, High inhibitors
Treatment: FVIIa
Activated factor VII (FVIIa) is one of two bypassing agents approved to treat bleeds in someone with a high-titer inhibitor. By using FVIIa to treat a bleed, the body can “bypass” the intrinsic pathway to clot formation, eliminating the need for Factor IX. FVIIa uses the extrinsic pathway to activate factor X and start the common pathway to a thrombin burst, leading to the formation of a strong, durable clot.
Condition: von Willebrand Disease
von Willebrand Disease (vWD) is the most common bleeding disorder, occurring equally in men and women. von Willebrand disease is a genetic disorder caused by a missing or defective von Willebrand factor (vWF), a clotting protein that works with factor VIII to help make platelets stick to the site of injury, forming the platelet plug. Some people with vWD also have low levels of factor VIII. There are different levels of severity of vWD, and different ways to treat it, depending on severity. Some people with less severe vWD may not even know that they have it.
Condition: von Willebrand Disease
Treatment: Desmopressin
When they have a bleed, some people with von Willebrand disease (vWD) can infuse or inhale desmopressin (DDAVP), which causes the body’s cells to release more von Willebrand factor and FVIII. von Willebrand factor helps to stabilize FVIII levels in the body by protecting factor VIII from being broken down. vWF helps create better platelet plugs and strong, durable clots.
Condition: von Willebrand Disease
Treatment: Replacement vWF+FVIII
People with von Willebrand disease (vWD) who have lower FVIII levels can infuse factor concentrate containing von Willebrand factor (vWF) and FVIII. vWF helps stabilize FVIII, so that it is not broken down in the body, and helps platelet plugs stick to the site of an injury, creating strong, durable clots.
Condition: von Willebrand Disease
Treatment: Replacement vWF
People with von Willebrand disease (vWD) who have adequate FVIII levels can infuse a factor concentrate that contains von Willebrand factor (vWF) only. Infused vWF can help stabilize the level of FVIII in the body by protecting FVIII from being broken down, and help platelets stick to the wound, creating better platelet plugs and strong, durable clots.
Factor XII
Factor XII starts the intrinsic pathway, which begins when an injury occurs and broken skin is exposed. Activated Factor XII goes on to activate Factor XI.
Factor XI
Factor XI activates Factor IX, which then activates Factor X.
Factor IX
Factor IX helps activate factor X, beginning the common pathway to clot formation. When the body doesn’t make enough Factor IX, people may have hemophilia B.
Factor VIII
Factor VIII helps activate Factor X, beginning the common pathway to clot formation. When the body doesn’t make enough factor VIII, people may have hemophilia A.
Von Willebrand factor
Von Willebrand factor (vWF) has two main roles in the body: it binds to Factor VIII, keeping it from being broken down by the body, and it helps platelets stick well to the site of injury, forming a strong platelet plug. When the body doesn’t make enough vWF, patients may have von Willebrand disease.
Factor X
Factors in the intrinsic and extrinsic pathways activate Factor X, beginning the common pathway to clot formation. Factor X helps activate prothrombin into thrombin.
Factor VIIa
Factor VIIa is one of the most important factors because it triggers both the start of primary hemostasis and it is the beginning of the extrinsic pathway of the coagulation cascade, where it activates factor X.
Factor Va
Factor Va, along with activated factor X, activates prothrombin (FII) into thrombin (FIIa).
Thrombin (IIa)
The coagulation cascade speeds up when thrombin is formed, creating a "thrombin burst." Thrombin causes fibrin to form, which strengthens the clot. The sooner the thrombin burst happens, the less damage a bleed can cause.
Fibrin (Ia)
Fibrin acts as a strong net around the platelet plug that stabilizes the clot and stops bleeding at the site of injury and remains until the injury has healed.
Clot
When the coagulation cascade works properly, a fibrin mesh forms around the platelet plug, creating a strong, durable clot.
Factor XIIIa
Factor XIIIa pulls fibrin strands tightly around the platelet plug, further stabilizing the clot.
Conditions
Inhibitors
Treatments