Hemostasis: Processes, Factors, Pathways, and Disorders

Hemostasis is the process by which blood clots to stop bleeding after an injury. It is a complex process with three main stages – vascular spasm, platelet plug formation, and blood coagulation. Hemostasis enables us to stop bleeding from injured blood vessels. Without it, we would bleed to death from even minor cuts. Understanding the hemostasis process is crucial for medical lab students.

Types of Hemostasis
There are two main types of hemostasis:

Primary Hemostasis
The initial immediate response involving vasoconstriction and platelet plug formation. It serves as an initial quick blockage to bleeding.

Secondary Hemostasis
Slower acting coagulation process where fibrin threads are formed to strengthen the platelet plug. It stabilizes the initial platelet plug.

Stages of Hemostasis
Hemostasis occurs in three main stages:

1. Vascular Spasm
   Reflex contraction of blood vessel in response to injury. This briefly reduces blood loss from the damaged vessels.
2. Platelet Plug Formation
   Platelets stick together and adhere to the exposed collagen in damaged blood vessels forming a temporary loose platelet plug.
3. Coagulation
   Complex interactions between coagulation factors, platelets and damaged endothelial surfaces lead to fibrin formation which stabilizes the platelet plug.

Vascular Spasm
The first response to vessel injury is vasoconstriction. The injured blood vessel undergoes vascular spasm, where smooth muscle in vessel wall contracts, reducing blood flow. This rapid vascular response reduces initial bleeding.

Platelet Plug Formation
Next, platelets stick to the exposed collagen in the damaged blood vessels. This process is called platelet adhesion. Platelets release chemicals like ADP, serotonin, and thromboxane A2. These chemicals recruit and activate more platelets which stick to each other and to the damaged tissue surface.

This forms a platelet aggregate or platelet plug. The platelet plug forms a temporary loose haemostatic seal to keep blood in vessels and limit further blood loss.

Coagulation Cascade
This stabilizes the initial platelet plug. It involves a complex cascade of chemical reactions between coagulation factors which eventually lead to fibrin thread formation.

There are two interlinked coagulation pathways intrinsic and extrinsic which merge:

Intrinsic Pathway
Internal damage and trauma activates factors XII, XI, IX and VIII. End result is fibrin formation.

Extrinsic Pathway
Tissue damage leads to release of tissue factor which binds factor VII. This leads activates factor X and also leads to fibrin formation.

Both pathways lead to activation of factor X. Activated factor X converts prothrombin (factor II) into thrombin (factor IIa). Thrombin converts fibrinogen into fibrin threads forming an interlocking network which stabilizes the platelet plug.

Clotting Factors
Clotting factors are essential proteins needed for the coagulation cascade. They are sequentially activated in the coagulation pathway.

Factor I (Fibrinogen): Inactive protein converted into fibrin strands
Factor II (Prothrombin): Inactive protein converted into thrombin
Factor III (Tissue Factor): Protein activating extrinsic pathway
Factor IV: Calcium ions
Factor V: Labile plasma protein accelerator
Factor VII: Serum procoagulant combining with tissue factor
Factor VIII: Labile plasma protein accelerator
Factor IX: Plasma thromboplastin component (PTC)
Factor X: Stuart-Prower factor
Factor XI: Plasma thromboplasin antecedent (PTA)
Factor XII: Hageman factor
Factor XIII: Fibrin stabilizing factor

Disorders of Hemostasis

There are two main categories:

1. Disorders where there is increased bleeding tendency
   Due to deficiency of platelets, clotting factors, or other hemostatic components. This can lead to excessive and spontaneous bleeding episodes.
2. Disorders which increase clotting tendency
   Excessive clotting blocks blood vessels causing strokes, heart attacks, DVT or pulmonary embolism.

The main disorders are:

Thrombocytopenia – Low platelet counts
Inherited – Thrombocytopenia absent radii syndrome
Acquired – Drug induced, infections (HIV, Hepatitis C), autoimmune

Coagulation Factor Deficiencies
Hemophilia A – Factor VIII deficiency
Hemophilia B – Factor IX deficiency
Von Willebrand Disease – Von Willebrand factor deficiency

Platelet Function Disorders
Impaired platelet plug formation
Inherited – Bernard Soulier syndrome
Acquired – renal disease, myelodysplastic syndromes

Thrombophilias – Excess clotting factors
Factor V leiden mutation
Prothrombin gene mutation G20210A
Antiphospholipid syndrome

Disseminated Intravascular Coagulation
Widespread clotting depletes platelets and coagulation factors

Key Term Definitions:

Hemostasis: Process where bleeding stops due to vasoconstriction, platelet plug formation and coagulation.

Primary Hemostasis: Initial vasoconstriction and platelet plug formation

Secondary Hemostasis: Coagulation stabilizing the platelet plug

Vascular Spasm: Reflex contraction of blood vessels reducing blood flow.

Platelet plug: Platelets aggregating and sticking to exposed vessels.

Coagulation Cascade: Complex reactions activating clotting factors.

Intrinsic Pathway: Internal activation of factors VIII, IX, XI, and XII.

Extrinsic Pathway: External tissue factor activation of factors VII and X.

Clotting Factors: Essential proteins numbered I to XIII needed for coagulation.

Thrombocytopenia: Low platelet count.

Hemophilia: Clotting factor VIII and IX deficiency with bleeding episodes.

Von Willebrand Disease: Von Willebrand factor deficiency impairing platelet plug formation.

Thrombophilia: Increased clotting tendency due to excess clotting factors.

Disseminated Intravascular Coagulation: Widespread clotting using up platelets and factors.