Hemostasis Overview

Hemostasis

• Hemostasis is a process that prevents blood loss from damaged blood vessels through clot formation.
• Hemostasis maintains blood in a fluid state.
• Coagulation proteins are involved in the hemostatic process.
• Deficiencies in coagulation proteins can lead to bleeding.

Primary Hemostasis

• Primary hemostasis involves the response of the vascular system and platelets to vessel injury.
• It involves vessel contraction, platelet aggregation, and adhesion to the subendothelium of the vasculature.
• Platelet adhesion requires von Willebrand factor (vWF) and platelet receptors.
• Platelet aggregation is stimulated by adenosine diphosphate (ADP) and stabilized by fibrinogen.
• Defects in platelet function or vWD can lead to bleeding.

Secondary Hemostasis

• Secondary hemostasis involves the coagulation system's response to vessel injury.
• This process controls bleeding from large wounds and is a continuation of primary hemostasis.
• The coagulation system involves a cascade of reactions that ultimately lead to the formation of a fibrin clot.

Vascular System

• The vascular system prevents bleeding through vessel contraction, diversion of blood flow from damaged vessels, and initiation of contact activation of platelets and the coagulation system.
• The ECs secrete vWF, P-selectin, ICAMs, and PECAMs.
• Smooth muscle and fibroblasts release tissue factor (TF).

Platelets

• Platelets are activated by exposed collagen in the basement membrane.
• They release various granular contents, including ADP, which attract more platelets to the site of injury.

Coagulation System

• The coagulation system is a cascade of reactions involving multiple coagulation factors.
• It is activated by tissue factor (TF), which binds to and activates factor VII (FVII).
• TF-FVIIa complex activates factor X (FX) and initiates the common pathway.
• The common pathway leads to the formation of thrombin.
• Thrombin converts fibrinogen to fibrin, forming a stable clot.

Serine Proteases and Inhibitors

• Serine proteases are enzymes involved in many physiological processes, including coagulation.
• They include thrombin, FXa, elastase, and trypsin.
• They play a role in inflammation and disease.
• Natural serine protease inhibitors regulate these enzymes.
• Antithrombin-III is a major inhibitor of thrombin.
• Antithrombin-III also inhibits factors XIIa, XIa, IXa, protein S, protein C, plasmin, and kallikrein.

Complement System

• The complement system is a part of the immune system.
• It is activated by plasmin.
• Cleavage of C3 into C3a and C3b.
• C3a causes increased vascular permeability.
• C3b is an opsonin.
• Cells express regulatory molecules to protect themselves from complement attack.

Activated Partial Thromboplastin Time (aPTT)

• The aPTT monitors the intrinsic pathway of the coagulation system.
• It measures the time it takes for plasma to clot after the addition of a reagent that activates the intrinsic pathway.
• Prolonged aPTT is found in disorders affecting the intrinsic pathway, such as hemophilia A and B.

Prothrombin Time (PT)

• The PT monitors the extrinsic pathway of the coagulation system.
• It measures the time it takes for plasma to clot after the addition of tissue thromboplastin, which activates the extrinsic pathway.
• Prolonged PT is found in disorders affecting the extrinsic pathway, such as vitamin K deficiency.

International Normalized Ratio (INR)

• The INR is a standardized measure of the PT.
• It corrects for differences in reagents used to perform the PT test.
• The INR is used to monitor the effectiveness of anticoagulant medications such as warfarin.

Hemostasis Disorders

• Hemostasis disorders can result from deficiencies in coagulation factors, platelets, or vascular integrity.
• Bleeding disorders can be due to inherited or acquired conditions.
• Examples include hemophilia, von Willebrand's disease, and thrombocytopenia.

Conclusion

• Hemostasis is a complex and tightly regulated process.
• It involves a delicate balance between procoagulant and anticoagulant factors.
• Dysregulation of hemostasis can lead to bleeding or thrombosis.