PLATELETS:
Platelets are referred to as thrombocytes because of their sealing function i.e.
they form a thrombus, or plug, when there is a break in the circulatory system.
Are about 40 times more common than leukocytes in the blood.
Normal count
the normal concentration of platelet in the blood is 150,000 – 450,000
platelets/[Link]. Average value is 300,000/[Link] .
Thrombocytopenia: when the plt count <150.000/[Link]( μL) while
thrombocytosis when the plt>450.000/[Link].
Life span: is 5 – 9 days average 7 days
Thrombopoiesis: is the process of platelet production or development .
All platelets are divided from cells in bone marrow called
megakaryoblasts,
The maturation of megakaryocytes is regulated by growth factor called
thrombopoietin.
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Platelets do not have nuclei .
Platelets are discoid-shaped packages of cytoplasm surround by a
membrane.
Platelets surface has many openings that extended deeply into the
interior of the structure which give the platelets a sponge-like
appearance.
Clotting factors such as factor I,(fibrinogen), factor V (labile factor) &
factor VIII (antihemophilic factor A) are adhere to these openings..
the membrane contain large amount of phospholipids [platelet factor
3(PF3)] which plays an important role in clotting process.
Cytoplasm: Rich in granules and organelles.
a- Alpha granules: Contain clotting factors, von Willebrand factor (vWF),
fibrinogen.
b- Dense granules: Contain serotonin, ADP, calcium, and ATP (promote
aggregation.)
c- actin & myosin(that can cause contraction of the platelet) these
contractile proteins are important in clot retraction).
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Factors Affecting Platelet Count
1. Age & Gender: Slight variations occur naturally.
2. Medications: Chemotherapy, heparin, aspirin, etc.
3. Infections & Diseases: Viral infections, leukemia, liver disease, etc.
Platelet Function:
Platelets are critical for hemostasis and other functions:
A. Hemostasis (Clot Formation)
1. Adhesion – Platelets adhere to exposed collagen at the injury site via von
Willebrand factor (vWF).
2. Activation – Platelets change shape, release granules, and express surface
receptors.
3. Aggregation – Platelets stick together using fibrinogen and form a plug.
4. Coagulation Cascade Support – Platelets provide a surface for clotting
factors.
5. Clot Retraction & Resolution – Platelets contract to stabilize the clot and aid
in healing.
B. Other Functions
1. Wound Healing – Release growth factors like PDGF (platelet-derived growth
factor).
2. Immune Response – Platelets interact with immune cells to fight infections.
Platelet Disorders:
A. Thrombocytopenia (Low Platelets)
B. Thrombocytosis (High Platelets)
C. Platelet Function Disorders
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[Link] causes:
1. Bone marrow failure (leukemia, aplastic anemia)
2. Increased destruction (ITP, DIC, heparin-induced thrombocytopenia)
3. Sequestration (hypersplenism)
4. Immune Thrombocytopenic Purpura (ITP): Autoimmune destruction of
platelets
5. Disseminated Intravascular Coagulation (DIC): Widespread clotting and
bleeding
• Symptoms: Easy bruising, petechiae, prolonged bleeding.
B. Thrombocytosis causes:
1. Primary: Essential thrombocythemia (bone marrow disorder)
2. Secondary: Infection, inflammation, cancer
• Symptoms: Increased clotting risk, stroke, or bleeding.
C. Platelet Function Disorders: Examples:
• Bernard-Soulier Syndrome: Deficiency of GPIb (platelet adhesion defect)
• Glanzmann’s Thrombasthenia: Deficiency of GPIIb/IIIa (platelet aggregation
defect)
Diagnosis of Platelet Disorders
A. Complete Blood Count (CBC): Determines platelet count (thrombocytopenia
vs. thrombocytosis).
B. Peripheral Blood Smear: Examines platelet morphology (size, shape,
granules.)
C. Platelet Function Tests:
• Bleeding Time: Evaluates platelet plug formation.
• Platelet Aggregometry: Measures response to agonists like ADP, epinephrine.
• Flow Cytometry: Detects glycoprotein deficiencies.
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D. Bone Marrow Biopsy :Assesses platelet production abnormalities.
Treatment Approaches
a. Thrombocytopenia:
Corticosteroids, IVIG (for ITP(
Platelet transfusion (if severe(
b. Thrombocytosis:
Aspirin (to reduce clotting risk)
Hydroxyurea (for essential thrombocythemia)
c. Platelet Function Disorders:
HEMOSTASIS, CLOTTING FACTORS, AND
RELATED DISORDERS
Hemostasis is the physiological process that prevents excessive blood loss after
injury while maintaining blood fluidity within the vessels. It involves platelets,
clotting factors, and blood vessels, ensuring a balance between clot formation
and clot dissolution.
Phases of Hemostasis
[Link] Spasm (Vasoconstriction)
• Immediate reflex contraction of blood vessels to reduce blood loss.
• Mediated by endothelin and thromboxane A2 (TXA2).
[Link] Hemostasis (Platelet Plug Formation)
• Platelets adhere to the exposed collagen via von Willebrand Factor (vWF.)
• Platelets activate, release granules (ADP, TXA2), and aggregate using
fibrinogen.
[Link] Hemostasis (Coagulation Cascade)
• Formation of a stable fibrin clot via the coagulation cascade.
[Link] Retraction & Fibrinolysis (Clot Resolution)
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• Clot contracts via actin-myosin in platelets.
• Plasmin dissolves the clot to restore blood flow.
Clotting Factors and the Coagulation Cascade:
The coagulation cascade consists of a series of enzymatic reactions that
ultimately form a fibrin clot. It occurs via three pathways:
A. The Three Coagulation Pathways
[Link] Pathway (Contact Activation Pathway(
• Triggered by exposure to negatively charged surfaces (e.g., collagen).
• Factors involved: XII → XI → IX → VIII → X
[Link] Pathway (Tissue Factor Pathway(
• Activated by tissue factor (TF) release from injured cells.
• Factors involved: VII → X
• Tested using Prothrombin Time (PT/INR)
[Link] Pathway (Final Clot Formation)
• Factor X activates prothrombin (Factor II) to thrombin (Factor IIa).
• Thrombin converts fibrinogen (Factor I) to fibrin (Factor Ia).
• Factor XIII stabilizes the fibrin clot.
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Key Coagulation Factors & Their Roles
Factor Name Function
I Fibrinogen fibrin clot
II Prothrombin Converts to thrombin
III Tissue Factor Activates extrinsic pathway
IV Calcium Required for clotting
V Labile Factor Cofactor for Factor X
VII Stable Factor Activates Factor X (extrinsic)
VIII Anti-hemophilic A Cofactor for Factor IX (intrinsic)
IX Anti-hemophilic B Activates Factor X (intrinsic)
X Stuart-Prower Factor Activates prothrombin
XI Plasma Thromboplastin Antecedent Activates Factor IX
XII Hageman Factor Activates intrinsic pathway
XIII Fibrin-Stabilizing Factor Cross-links fibrin
Disorders of Hemostasis:
A. excessive bleeding (hemorrhagic disorders)
B. excessive clotting (thrombotic disorders).
A. Hemorrhagic Disorders (Bleeding Disorders)
[Link] (Deficiency of clotting factors(:
• Hemophilia A: Factor VIII deficiency.
• Hemophilia B: Factor IX deficiency.
• Symptoms: Prolonged bleeding, hemarthrosis (joint bleeding.)
[Link] Willebrand Disease (vWD):
• Deficiency of von Willebrand Factor, leading to platelet dysfunction. •
Symptoms: Easy bruising, nosebleeds, menorrhagia.
[Link] Intravascular Coagulation (DIC:
• Widespread clotting followed by bleeding due to depletion of clotting factors.
• Causes: Sepsis, trauma, malignancy, obstetric complications.
• Lab findings: ↑ PT, ↑ aPTT, ↓ platelets, ↓ fibrinogen, ↑ D-dimer.
[Link] Disease & Vitamin K Deficiency: The liver synthesizes most clotting
factors.
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• Vitamin K is required for Factors II, VII, IX, X production.
B. Thrombotic Disorders (Excessive Clotting)
[Link] Vein Thrombosis (DVT) & Pulmonary Embolism (PE)
• Formation of clots in deep veins, which may embolize to the lungs.
• Risk factors: Immobility, surgery, pregnancy, cancer, Factor V Leiden
mutation.
[Link] V Leiden Mutation : Mutation makes Factor V resistant to
inactivation by Protein C, leading to hypercoagulability.
[Link] Syndrome (APS(: Autoimmune disorder causing recurrent
clots and pregnancy loss.
[Link] C, Protein S , or Antithrombin III Deficiency:
• These natural anticoagulants help prevent excessive clotting.
•Deficiencies increase thrombosis risk.
Diagnostic Tests for Hemostasis Disorders
A. Screening Tests
a. Complete Blood Count (CBC): Checks platelet count.
b. Prothrombin Time (PT): Assesses extrinsic pathway (Factor VII.)
c. Activated Partial Thromboplastin Time (aPTT): Assesses intrinsic pathway
(Factors VIII, IX, XI, XII.)
d. Thrombin Time (TT): Assesses fibrin formation.
B. Specialized Tests
a. Mixing Studies: Differentiate factor deficiency vs. inhibitor.
b. D-Dimer Test: Elevated in DIC, DVT, and PE.
c. Factor Assays: Measure levels of specific clotting factors.
d. Von Willebrand Panel: Tests vWF antigen and function.
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