#hemostasis

Blood clotting is a complex process that involves platelets, clotting factors, and calcium. When a blood vessel is damaged, platelets stick to the area and release chemicals that activate clotting factors. These factors then form a mesh of fibrin, which traps blood cells and forms a clot.

Primary hemostasis: This is the initial stage of blood clotting, which occurs immediately after a blood vessel is injured. It involves the formation of a platelet plug at the site of injury. Platelets are small blood cells that help to stop bleeding by clumping together and forming a mesh. The mesh traps red blood cells and other blood components, which helps to seal the injured blood vessel.

Secondary hemostasis: This is the second stage of blood clotting, which occurs after the platelet plug has formed. It involves the formation of a fibrin clot, which is a mesh of protein fibers that strengthens the platelet plug and prevents it from breaking apart. The fibrin clot is formed by a series of reactions called the coagulation cascade. The coagulation cascade is a complex process that involves many different proteins, called clotting factors.

The coagulation cascade can be divided into two pathways: the intrinsic pathway and the extrinsic pathway.

The intrinsic pathway: This pathway is activated when blood comes into contact with damaged tissue or collagen, a protein found in the walls of blood vessels. The intrinsic pathway is also activated by certain substances released from platelets.

The extrinsic pathway: This pathway is activated when tissue factor, a protein found in the tissues, is exposed to blood. Tissue factor is released when blood vessels are injured.

Both the intrinsic and extrinsic pathways lead to the activation of factor X, which is a clotting factor that plays a key role in the formation of the fibrin clot.

Once factor X is activated, it triggers a series of reactions that lead to the formation of fibrin. Fibrin is a protein that forms long, thread-like fibers. These fibers entangle the platelets and other blood components, forming a strong, mesh-like clot.

The blood clot eventually dissolves, but this process takes several days. The dissolution of the clot is necessary to allow blood to flow freely again.

The blood coagulation process is a complex and tightly regulated process. There are many factors that can affect the clotting process, including:

Age: Children have a more active clotting system than adults. This is why they are more likely to bleed from minor cuts.

Gender: Women have a more active clotting system than men. This is why they are more likely to develop blood clots.

Medications: Some medications, such as aspirin and warfarin, can interfere with the clotting process.

Medical conditions: Some medical conditions, such as hemophilia and von Willebrand disease, can cause the blood to clot too easily.

Blood clotting is a vital process that helps to prevent excessive bleeding. However, it is important to maintain a balance between clotting and bleeding. Too much clotting can lead to blood clots, which can be dangerous. Too little clotting can lead to excessive bleeding.

To conclude, Blood coagulation is a complex and dynamic process that involves multiple factors and feedback mechanisms. It is essential for maintaining hemostasis and preventing excessive blood loss or thrombosis (formation of abnormal blood clots). Blood coagulation disorders can result from defects in clotting factors, platelets, or endothelial cells, leading to bleeding or thrombotic complications.

3 key components of the coagulation cascade:

Calcium ions, which are required for several key reaction steps.

Coagulation factors, which are the driving forces of the cascade; they comprise proenzyme factors are transformed to active enzymes, and are signified by the lower case "a." Many coagulation factors are synthesized by the liver; thus, coagulation disorders are associated with liver disease.

Co-factors are reaction accelerators; they form complexes with activated coagulation factors and calcium ions.

2 Pathways:

Traditionally, these pathways have been categorized as "intrinsic" and "extrinsic," but modern models emphasize their cooperation in thrombin formation.

Endothelial rupture exposes tissue factor to the blood; because tissue factor is exogenous to the blood, it is the start of the so-called "extrinsic" pathway(tissue factor is also known as thromboplastin or CD142).

Tissue factor activates coagulation factor VII, and, with calcium, forms a complex that activates factor IX (this complex is sometimes called extrinsic tenase).

Activated factor IX, with calcium and co-factor VIIIa, activates factor X.

Activated factor X combines with calcium and co-factor Va to form prothrombinase, which is the complex that transforms prothrombin (aka, factor II) to thrombin (factor IIa).

Thrombin converts fibrinogen to fibrin, which forms a meshwork that surrounds the aggregated platelets and traps other materials, including red and white blood cells and serum.

Return to the aggregated platelets to show how they influence thrombin production; because all the elements in this pathway are inherent to the blood, this is traditionally called the "intrinsic" pathway.

The negative surface of activated platelets activates Factor XII (aka, Hageman factor).

Factor XI Ia activates factor XI.

Factor XIa activates factor IX, which, as we've seen, forms a complex that ultimately leads to the production of thrombin and conversion of fibrinogen to fibrin.

Thrombin has other, indirect ways of promoting clotting:

It activates co-factors VIII and V, and factor XI; thus, it promotes its own production.

Thrombin also ensures the stability of the clot: show that it activates factor XIII, aka, fibrin stabilizing factor, which, as its name implies, strengthens the bonds of the fibrin mesh of the clot.

Retraction

Soon after the clot is formed, retraction occurs: the platelets contract and expel serum.

Serum lacks fibrinogen and clotting factors, so it cannot coagulate.

Thrombin also acts outside of the coagulation cascade via protease activation receptors (PARs):

Thrombin promotes platelet activation and release of thromboxane A2 for platelet plug formation.

It triggers endothelial activation and release of anticoagulants.

Thrombin also up-regulates pro-inflammatory mediators, such as cytokines and chemokines, implicating it in inflammatory conditions.

Endogenous anti-coagulation mechanisms:

Fibrin fibers absorb thrombin, which prevents excessive clotting.

Unabsorbed thrombin combines with anti-thrombin III, which neutralizes it.

Heparin, which is normally circulating in small concentrations but can be administered in higher doses, increases the effectiveness of anti-thrombin III and removes factors IX, X, XI, XII. Thus, it is prescribed to prevent thrombosis.

Healthy, intact endothelial cells produce nitric oxide, prostacyclin, and tissue plasminogen activator (t-PA) to prevent platelet adhesion and clot formation.

Fibrinolysis

Once the vessel wall heals, the clot must be removed via fibrinolysis, the breakdown of the fibrin mesh.

To illustrate, redraw the vessel, and show a platelet trapped by fibrin fibers.

Plasminogen binds to the fibrin; plasminogen is a proenzyme produced by the liver.

Endothelial cells release tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), which bind to fibrin and cleave plasminogen to form active plasmin. Recall that thrombin itself is a stimulus for t-PA release.

Plasmin breaks down fibrin, fibrinogen, and some coagulation factors to dissolve the clot.

Fibrinolysis produces fibrin degradation products (FDPs), most notably D-dimer, which is measured to assess thrombotic states (an elevated result may indicate excessive thrombotic states).

When not bound to fibrin, plasminogen and plasmin activity is inhibited:

In a positive feedback cycle, plasmin also converts t-PA and u-PA into their more active forms, which promotes further fibrinolysis.

Unbound t-PA and u-PA are inhibited by plasminogen activator inhibitor 1 (PAI-1).

Alpha-2 antiplasmin inhibits unbound plasmin.

Vitamin K

Vitamin K is critical to hepatic synthesis of prothrombin and factors VII, IX, and X.

30.01.2019

So instead of paying attention in clinical chemistry, my friends and I created a game of thrones bingo, who is gonna die and who will turn into a white walker basically.