Disorders of Hemostasis

Hemostasis

It is the stoppage of blood flow (the process by which the body stops the bleeding after an injury).

Component of Hemostasis: Platelets

Platelets (thrombocytes)

• They’re anuclear (does not have a nucleus)

• Originate from pluripotent stem cell - myeloid stem cell - megakaryocyte

• Thrombopoetin stimulates platelet production  → Thrombopoetin is released by the liver

Components of Hemostasis: Plasma Clotting Factors

• Factors I-XII are all mostly synthesized by the liver

• The Activation Clotting Factors leads to → The Clotting Cascade

Unique Clotting Factors - Factor X

• Factor X (both pathways converge here)

Factor I and Factor Ia

Factor I - Fibrinogen; when activated is Factor Ia - Fibrin

Factor II and Factor IIa

Factor II - Prothrombin; when activated is Factor IIa - Thrombin

Factor IV

Calcium

Vitamin K Clotting Factors

The Clotting Factors that need Vitamin K are:

• Factor II - Prothrombin

• Factor VII 

• Factor IX

• Factor X

Clotting Cascade

Components:

• INtrinsic Pathway - slow (1 to 6 mins), happens when damage to the blood vessel wall is done). First factor to activate → Factor XII

• EXtrinsic Pathway - faster (15 secs); happens outside the blood vessel wall. First factor to activate → Factor III: Tissue Factor

• Both pathways converge at factor X - Factor II → Factor IIa (Prothrombin → Thrombin), Factor I → Factor Ia (Fibrinogen → Fibrin)

Be able to explain the Clotting Cascade

5 Steps of Hemostasis

1. Vessel Spasm/Vasoconstriction

2. Formation of Platelet Plug

3. Blood Coagulation (Clotting Cascade)

4. Clot Retraction

5. Clot Dissolution

1. Vessel Spasm/Vasoconstriction

a. Immediate response to vessel injury.

b. Smooth muscle in the vessel wall contracts → reduces blood flow and limits blood loss.

c. Mediated by endothelin, thromboxane A₂, and neural reflexes.

2. Formation of Platelet Plug

Platelet Plug Formation 

a.Platelets adhere to exposed collagen via von Willebrand factor (vWF).

b. Activated platelets release ADP, thromboxane A₂, and serotonin → recruit and activate more platelets.

c. Platelets aggregate to form a temporary plug.

3. (Coagulation) Clotting Cascade

Coagulation Cascade (Secondary Hemostasis)

a. Intrinsic pathway: triggered by contact with exposed collagen (Factors XII, XI, IX, VIII).

b. Extrinsic pathway: triggered by tissue factor (Factor III) and Factor VII.

c. Both converge on the common pathway: Factor X → Xa → converts prothrombin (II) to thrombin 

4. Clot Retraction 

Clot Retraction 

a. Platelets contract, pulling fibrin strands together.

b. This reduces clot size and brings wound edges closer.

c. Fibroblasts and smooth muscle cells migrate in for tissue repair.

5. Clot Dissolution (fibrinolysis)

Fibrinolysis (Clot Removal)

a.Once healing begins, the clot is dissolved.

b. Plasminogen is activated to plasmin, which digests fibrin.

c. Prevents excessive clotting and restores normal blood flow.

Bleeding Disorders: Thrombocytopenia

• caused by decreased in circulating platelet count (< 150,000/μL)

• increases the risk of bleeding

Thrombocytopathia 

• there are plenty of platelets, they are just not working

• caused by the use of aspirin (ASA) and NSAIDs

• can be caused by disorders of adhesion (von Willebrand disease)

Coagulation Disorders: Hemophilia A

• X-linked recessive disorder

• Factor VIII deficiency

• Treatment: Factor VIII replacement therapy

Coagulation Disorders: von Willebrand Disease

• Autosomal Dominant Disorder

• Deficiency or defect in von Willebrand Factor (vWF)

• Treatment: mild- moderate bleeding: DDAVP (desmopressin acetate), analog of vasopressin (ADH)

Disseminated intravascular coagulation (DIC)

• First problem: clotting then bleeding (clotting, bleeding, clotting, bleeding pattern)

• clotting comes first as a result of excessive thrombin generation

• basically, steps 3 and 5 of hemostasis are repeated over and over until all platelets and clotting factors have been used up

• Manifestations: bleeding (their organs are being filled with tiny blood clots), hypoxia, and organ damage