Bleeding Disorders: A Study Notes

The Overview

Bleeding disorders occur when hemostasis (the process of stopping bleeding) is impaired.
Hemostasis involves two stages:

1. Primary Hemostasis → Blood vessel + Platelet phase

2. Secondary Hemostasis → Clotting factor (coagulation cascade) phase

 Primary Hemostasis

Definition

Formation of the platelet plug at the site of vascular injury.

Key Players

• Blood vessel integrity

• Platelets

• Von Willebrand Factor (vWF)

• Fibrinogen

Normal Process

1. Vascular Spasm

   • Blood vessel constricts to reduce bleeding.

   • Mediators: Endothelin, Serotonin, Thromboxane A₂

2. Platelet Adhesion

   • Injury exposes collagen (negatively charged).

   • vWF acts as a bridge:

     • Binds to collagen via one receptor.

     • Binds to platelet receptor GP1b via another.

3. Platelet Activation

   • Platelets become spiky and sticky.

   • Release ADP, Thromboxane A₂ (activates nearby platelets).

4. Platelet Aggregation

   • Platelets stick to each other via fibrinogen bridges and GP IIb/IIIa receptors.

5. Temporary plug forms → reinforced later by fibrin (secondary hemostasis).

Primary Bleeding Disorders

Caused by:

• Blood vessel abnormalities

• Platelet abnormalities (quantity or function)

1. Platelet Quantity Problems (Thrombocytopenia)

A. Decreased Production

• Bone marrow failure:

  • Aplastic anemia → No blood cell production

  • Acute leukemia → Marrow crowded by blasts

  • Myelodysplastic syndrome → Dysfunctional marrow output

B. Increased Destruction/Consumption

• Immune Thrombocytopenic Purpura (ITP) → Autoantibodies destroy platelets

• DIC (Disseminated Intravascular Coagulation) → Clots form throughout body → consumes platelets → paradoxical bleeding

C. Sequestration (Hypersplenism)

• Splenomegaly (e.g. from portal hypertension due to cirrhosis)

• Enlarged spleen traps platelets

2. Platelet Function Problems (Qualitative Disorders)

Disorder	Defect	Mechanism
Bernard–Soulier Syndrome	GP1b deficiency	Platelets can't bind vWF
Glanzmann Thrombasthenia	GP IIb/IIIa deficiency	Platelets can’t bind fibrinogen or aggregate
von Willebrand Disease (Types 1–3)	↓ or dysfunctional vWF	Platelet adhesion impaired
Drug-induced (Aspirin, NSAIDs)	Inhibit Thromboxane A₂ synthesis	↓ Vasoconstriction & ↓ platelet activation

3. Blood Vessel Problems

• Ehlers–Danlos Syndrome → Collagen defect

• Vitamin C deficiency (Scurvy) → Impaired collagen synthesis

• Excess corticosteroids → Weak vessel walls

Secondary Hemostasis

Definition

Formation of the fibrin mesh that stabilizes the platelet plug.

Key Players

• Clotting factors (I–XIII) — mostly produced by liver

• Calcium (Ca²⁺)

• Vitamin K

Pathways

1. Intrinsic Pathway (stimulated by negatively charged surfaces)

• Factors: XII → XI → IX (+ VIII) → X

• Measured by PTT (Partial Thromboplastin Time)

2. Extrinsic Pathway (stimulated by tissue damage)

• Factors: Tissue Factor + VII → X

• Measured by PT (Prothrombin Time)

3. Common Pathway

• X → V → II (Prothrombin → Thrombin) → I (Fibrinogen → Fibrin)

• XIII cross-links fibrin → stable clot

Secondary Bleeding Disorders

1. Inherited Disorders

Disorder	Factor Deficiency	Inheritance	Key Test Finding
Hemophilia A	Factor VIII	X-linked recessive	↑ PTT
Hemophilia B (Christmas Disease)	Factor IX	X-linked recessive	↑ PTT
Hemophilia C	Factor XI	Autosomal recessive	↑ PTT
von Willebrand Disease	↓ vWF → ↓ Factor VIII	Autosomal dominant/recessive	↑ PTT ± ↑ BT (Bleeding Time)

2. Acquired Disorders

A. Vitamin K Deficiency

• Affects factors II, VII, IX, X

• Needed for carboxylation → activation

• Causes:

  • Poor diet (↓ leafy greens, meat, dairy)

  • Antibiotic use (↓ gut flora)

• ↑ PT and PTT

B. Liver Disease

• ↓ synthesis of all clotting factors → prolonged PT & PTT

C. Warfarin Therapy

• Inhibits Vitamin K epoxide reductase

• Mimics Vitamin K deficiency

D. Heparin Therapy

• Activates Antithrombin III → inhibits Thrombin (IIa) → ↓ fibrin formation

E. Disseminated Intravascular Coagulation (DIC)

• Massive activation of clotting cascade → widespread microthrombi

• Consumes platelets + clotting factors

• Leads to bleeding and thrombosis

• Causes: Sepsis, trauma, malignancy, obstetric complications

Key Diagnostic Tests

Test	Measures	Indicates
Bleeding Time (BT)	Platelet function	Primary hemostasis
PT (Prothrombin Time)	Extrinsic pathway (VII)	Warfarin, liver disease
PTT (Partial Thromboplastin Time)	Intrinsic pathway (VIII, IX, XI, XII)	Hemophilias, Heparin
Platelet Count	Platelet quantity	Thrombocytopenia
D-dimer	Fibrin degradation product	DIC, thrombosis

Summary Table

Type	Defect	Key Examples	Key Tests
Primary Bleeding Disorder	Platelet or vessel problem	ITP, vWF disease, Glanzmann, Bernard-Soulier, Scurvy	↑ Bleeding time, normal PT/PTT
Secondary Bleeding Disorder	Coagulation factor defect	Hemophilia, Vitamin K deficiency, DIC, liver disease	↑ PT/PTT