Platelets function and bleeding control

Question 1

What are the physical characteristics of platelets?

Answer 1

• 1-4 micrometers in diameter (the smallest cell in the blood)
• They are formed in the bone marrow from megakaryocytes
• They have mitochondria (since they do a lot of work and need energy)
• There are around 150,000 to 450,000 platelets per microliter in our bodies

Question 2

Where are the platelets stored?

Answer 2

• There are no platelets stored in the bone marrow
• Once they are formed they are only found in the circulation where 30% of them are in active and 70% are active

Question 3

What are the characteristics of platelets?

Answer 3

1) They have glycoproteins in their surface receptors which helps them adhere to the endothelium and injured areas

2) Contractile proteins (actin, myosin, & thrombosthenin) which help in the retraction of the clot

3) Mitochondria for the production of ATP

4) Endoplasmic reticulum to store Ca

5) Ribosomes to make proteins (from the stored mRNA within them)

6) Alpha granules (they contain growth factors, IGF-1 “Insulin-like growth factor”, PDGF, TGF-b “Transforming-growth factor-b”, & Platelets factor-4, which helps in the repair and growth of the vascular wall)

7) Clotting proteins (thrombospondin, fibronectin, factor V, vWF (von Willebrand Factor)

8) Adhesion molecules (P-selectin and CD63 which helps in the adhesion of platelets

Question 4

Describe the process of platelet production (thrombopoiesis)

Answer 4

• With a life span of 8-12 days, then they are phagocytized by macrophages in the spleen
• They are produced from megakaryoblasts - promegakaryocytes- megakaryocyte, and then the megakaryocyte will fragment into tiny platelets
• Thrombopoiesis is regulated by thrombopoietin (MGDF “produced by the liver and kidneys”), Interleukin-6 and 11

Question 5

What are the functions of platelets?

Answer 5

1) Maintains blood hemostasis

2) Forms platelet plug

3) Facilitates blood coagulation

4) Contraction of the clot after it forms

5) Wound repair via platelet growth factor

Question 6

What is thrombocytosis and what are its causes?

Answer 6

• An increase in the platelet count >450,000/ul:

1) Primary:
- Unknown cause, where there is a sustained proliferation of megakaryocytes

2) Secondary (reactive):
- Inflammation (due to the increase in interleukin 6 & 11)
- Surgery (as it increases inflammation)
- Splenectomy (It removes the old platelets so the body tries to compensate
- Iron deficiency (increases thrombopoiesis)

Question 7

What is thrombocytopenia and what are its causes?

Answer 7

• Decreased platelet count <150,000

1) Bone marrow disorders:
- Hypoplasia
- Radiation
- Drugs
- Idiopathic

2) Peripheral destruction:
- Liver disease
- Hypersplenism
- Immune reactions

• When platelets count is below 50,000 bleeding occurs (signs of bruises and ecchymosis)

Question 8

Describe the mechanism of platelets

Answer 8

1) Injury to the endothelium

2) Vascular spasm (myogenic contraction due to pain nerve impulses and the factors released by damaged tissue and platelets)

3) Platelet plug formation (primary homeostasis)

4) Fibrin formation (secondary homeostasis “added to the platelet plug to make it more stronger and keep it in place)

5) Clot dissolves (Vascular healing)

Question 9

What are the factors that induce vascular spasm?

Answer 9

1) Tissue factors (component of thromboplastin/factor III)

• Secreted by smooth muscle cell of B.Vs, and the fibroblast that surround them

2) Inspectors (Factor XII, & vWF)
- They are in the blood all the time to patrol for any injury
- Factor 7 is secreted by the liver while vWF is secreted by endothelial cells and platelets

Question 10

How does the platelet plug form?

Answer 10

1) Damaged BV

2) The collagen is exposed

3) Circulating von Willebrand Factor binds to the exposed collagen

4) Circulating platelets will then bind to the vWF on the collagen

5) The sticky platelets will then release thromboxane A2 and ADP which will attract more platelets

6) Platelet plug is formed

Question 11

What are the things that prevent the formation of a platelet plug?

Answer 11

In an undamaged BV:

1) Collagen is not exposed so there is no binding of vWF

2) The endothelial cells secretes prostacyclins and nitric oxide which prevents the aggregation of platelets

Question 12

Describe the process of fibrin formation (coagulation cascade)

Answer 12

• Platelets alone are like stones they will plug the gap but they need fibrin (a cement) to stop any bleeding
• Fibrin (water insoluble) formation requires a sequence of clotting factors reaction (coagulation cascade) which starts 15-20 seconds after severe trauma and 1-2 minutes in minor trauma

1) Prothrombin activator is released in response to blood vessel damage

2) The prothrombin activator (Factor 5) converts prothrombin (Factor -2) into thrombin

3) Thrombin will then convert fibrinogen (F-1) into fibrin

• Endothelial damage can be extrinsic (damage to tissue outside the BV “involves connective tissue, fibroblasts, and smooth muscles activated by tissue factor”) or intrinsic (damage to the BV itself “involves endothelial tissue and connective tissue activated by Factor 7 and vWF”)
• In the intrinsic pathway only the endothelium is damaged unlike in the extrinsic pathway where the whole BV is damaged
• Tissue factor is a component of Factor III (thromboplastin)

Question 13

What breaks the fibrin clots?

Answer 13

They are broken down by the fibrinolytic activity

Question 14

Describe the mechanism of action of the extrinsic pathway

Answer 14

Tissue trauma will release tissue factor from damaged tissue, TF is a proteolytic enzyme that cleaves proteins (converts factor 7 to 7a and factor 5 to factor Xa and then to prothrombin activator (as it combines with Ca and factor v)

• Not imp to memorize

Question 15

Describe the mechanism of action of the intrinsic pathway

Answer 15

• Internal trauma in the blood vessel causes activation of factor XII
• Factor X is then activated
• Factor X combines with Ca, factor V & Platelets phospholipids to form the complex Prothrombin activator
• The ultimate goal of both the intrinsic and extrinsic pathways is to form thrombin

Question 16

Describe the steps in the formation of a blood clot from prothrombin

Answer 16

1) Prothrombin is synthesized in the liver, and vitamin K is required for its activation

2) The prothrombin activator will then convert prothrombin to thrombin which will remove 4 molecules from each fibrinogen molecule to make fibrin monomers (which will act like a cement)

3) Thrombin will then convert fibrinogen which is synthesized in the liver to fibrin, which a lot of them will fuse together to form fibrin fibers that enmesh blood cells in a clot like fish in a net

Question 17

What is the role of the liver in clot formation?

Answer 17

• Synthesizes almost all clotting factors
• Advanced liver disease results in bleeding disorders and disseminated intravascular coagulation (DIC “its life-threatening”)

Question 18

What is the role of calcium in clot formation?

Answer 18

• Accelerates all clotting reactions
• Blood collection tubes contain chemicals like oxalate, citrate, and EDTA to bind to calcium and prevent the formation of clots

Question 19

What is the role of vitamin K in clot formation?

Answer 19

• It is required for the activation of factors II, VII, IX, & X
• Vitamin K deficiency is associated with bruising, petechiae, and the formation of hematomas

Question 20

How does the clot go?

Answer 20

• The clot retracts pulling the blood vessel edges together, which is activated by thrombin and calcium and mediated by contractile proteins in the platelets
• The clot is then lysed:

1) Blood clot causes the slow release of TPA from the endothelium

2) Plasminogen (synthesized by the liver) is released into the blood and incorporated into blood clots

3) The TPA will then break the inactive plasminogen into active plasminogen which will break down the fibrin mesh, and the macrophages will phagocytize all of the trapped RBC

• TPA is used clinically to treat diseases that features blood clots