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Platelet structure and function
ﻣَﺎ ﺳَﻌَﻰٰ وَأَن ﻟ˶ ﻴْﺲ َ ﻟِﻺِْﻧﺴَﺎن ِ إِﻻ˶
❖ Describe formation and development of platelets. ❖ Understand platelet normal ultrastructure. ❖ Describe the functions of different platelets organelles and surface receptors. ❖ Describe the mechanism of platelet functions. ❖ Relate membrane receptors and granule content to normal function in hemostasis and bleeding (platelet) disorders.
➔ Team leader: Rahaf AlShammari, Abdulrahmen AlHayssoni ➔ Team members: ◆ Yazeed AlKhayyal, Khalid AlMutairi, Abdullah AlSargani ◆ Majd AlBarrak, Renad AlMegrin ◆ Shahad AlTayash, Hadeel AlMukaynizi ◆ AlAnoud AlEssa, Dana AlKadi
★ Special thanks for Sultan AlNasser!
Platelets
Formed by fragmentation from megakaryocytes.
Site of formation
Bone marrow
Platelet
GP Ia GP VI
TPα
GP Ib-IX- V
GP IIb-III a
P2Y 12
vW factor
Fibrinogen, vWF
Collagen
TXA
ADP
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Platelet Receptors
- (GP Ia,GP VI) ○ binds to collagen [it will be exposed under the endothelium in injuries].
- (GP Ib-IX-V) ○ binds to vW factor (it's a clotting factor from endothelial cells).
- (GP IIb-IIIa) ○ binds to fibrinogen [its present in α granules & plasma in inactive state, and vWF).
- (TPα) ○ binds to TXA2.
- (P2Y 12 ) ○ binds to ADP.
Extremely important!! You have to memorize the name of each receptor and what does it bind to
Functional characteristics
● Motile : Actin and Myosin molecules. ● Active : Endoplasmic reticulum, Golgi apparatus and mitochondria. ● Enzymes system: synthesis of prostaglandins ● Granules (alpha and delta/dense)
Q: What are the functional characteristics of platelets? may come as SAQ!
SAQ The sequence is very important
General functions of the platelets
Hemostasis
- Vascular phase
- Platelet phase
- Coagulation phase
- Fibrinolytic phase
Hemostatic mechanisms
- Vessel wall
- Platelet
- Blood coagulation
- Fibrinolytic system
Platelet activation
Platelet activation
What's the main function of the platelets? Initial arrest of bleeding by formation of primary hemostatic plug, the mechanism is:
Adhesion Shapechange Aggregation (^) reaction^ Release retractionClot
4. Secretion
5. Clot reaction
Myosin and actin filaments in platelets are stimulated to contract during aggregation further reinforcing the plug and help release of granule contents
Resting platelets Activated platelet Spread platelet (cover the injured area better)
4- Secretion (release reaction phase):
- ADP strong activator of platelets [makes it sticky]> activate aggregation.
- 5HT vasoconstriction.
- Platelet phospholipid (PF3) clot formation.
- Thromboxane A2 (TXA2) is a prostaglandin formed from arachidonic acid. It is an example of +ve feedback ○ Function: ■ Vasoconstriction (decreasing blood flow through the injured vessel) ■ Platelet aggregation (TXA2 inhibited by aspirin). (Aspirin will inhibit cyclooxygenase enzyme)
Platelet haemostatic plug formation
➢ Platelets activated by adhesion ➢ Extend projections to make contact with each other ➢ Release: thromboxane A2, serotonin & ADP >> activating other platelets ➢ Serotonin & thromboxane A2 are vasoconstrictors decreasing blood flow through the injured vessel. ➢ ADP causes stickiness and enhances aggregation
Don’t memorize the coagulation cascade! The only thing you should know is the role of platelets in fibrin formation: ● For coagulation to happen we need cellular contribution, mainly platelets. Hence, the name Cell Based Model. ● When the platelets gets activated, we have the PF3 that is usually inside the platelet. When platelet is activated the PF3 will go to the surface of the platelet (and we mentioned how PF3 is important for clot formation) and this means that the reaction of coagulation happens on the surface of cell membrane. The product of coagulation is thrombin. ● Thrombin will convert fibrinogen (inactive form) to fibrin (active form)
Role of platelet in blood coagulation
(The cell based model of blood coagulation)
اﻟﻠﻲ ﻣﺮوق ﻳﺘﺨﻴﻞ ﻧﻔﺴﻪ platelet وﻳﺸﻮف اﻟﻔﻴﺪﻳﻮ, ﻳﻮﻧﺲ ﺗﺮا ﻳﺘﺰﺣﻠﻘﻮن
Platelet aggregation:
● Platelets are activated when brought into contact with collagen exposed when the endothelial blood vessel lining is damaged. ● Activated platelets release a number of different coagulation and platelet activating factors. ● Transport of negatively charged phospholipids to the platelet surface; provide a catalytic surface for coagulation cascade to occur. ● Platelets adhesion receptors (integrins): Platelets adhere to each other via adhesion receptors forming a hemostatic plug with fibrin. ● Myosin and actin filaments in platelets are stimulated to contract during aggregation further reinforcing the plug and help release of granule contents ● GPIIb/IIIa: the most common platelet adhesion receptor for fibrinogen and von Willebrand factor (vWF)
Summary of platelet activation:
Normal endothelium secrete: ● Prostacyclin PGI ● ● NOADP phosphate All of them prevent the aggregation
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Bleeding disorders:
Bleeding can result from:
Platelet defects:
● deficiency in number (thrombocytopenia) ● defect in function
Thrombocytopenia the causes of decreased platelet counts are:
● Leukemia or lymphoma ● Cancer treatments such as radiation or chemotherapy ● Various anemias ● Toxic chemicals ● Medications: diuretics, chloramphenicol ● Viruses: chickenpox, mumps, Epstein-Barr, parvovirus, AIDS ● Alcohol in excess ● Genetic conditions: Wiskott-Aldrich, May-Hegglin
I. Decreased production II.^ Increased destruction
Autoimmune diseases: Idiopathic (immune) thrombocytopenic purpura Medications: quinine, antibiotics containing sulfa, Dilantin®, vancomycin, rifampin, heparin-induced thrombocytopenia Surgery: man-made heart valves, blood vessel grafts, bypass machines Infection: septicemia Pregnancy: about 5% of pregnant women develop mild decrease Thrombotic thrombocytopenic purpura Disseminated intravascular coagulation
III. Abnormal distribution
Normally healthy people always get minor injuries, especially in small blood vessels, but it doesn’t show because the platelets are doing their role well. Signs of platelet dysfunction: Hemophilia, bruises (easily bruised without trauma), nose bleeding (epistaxis), abnormal menstrual cycle,
Congenital disorder Can congenital or acquired Acquired platelet disorder? A person taking aspirin
● Partial clotting of specimen ● EDTA-platelet clumping ● Platelet satellitism around WBCs ● Cold agglutinins ● Giant platelets
IV. Pseudothrombocytopenia
Splenomegaly with sequestration in the spleen.
Platelet Activation
Platelet
Collagen (GP Ia, GP VI)
TXA
ADP
GP Ib-IX-V (vW Factor)
GP IIb-IIIa (Fibrinogen, vWF)
Platelet
Collagen (GP Ia, GP VI)
TXA
ADP
GP Ib-IX-V (vW Factor)
GP IIb-IIIa (Fibrinogen, vWF)
Bernard-Soulier Syndrome Glanzmann Thrombasthenia
Lost
Lost
Tests of Platelet Functions:
● Bleeding time (Duke method) ● Peripheral smear and Platelet count ● Electron-microscopy ● Platelet Aggregation ● Platelet Function Analyzer (PFA- 100) ● Flow-cytometry ● Granule release products
How to investigate for a platelet disorder?
Deficiency of glycoprotein Ib It is a giant platelet disorder, meaning that it is characterized by abnormally large platelets.
Abnormal platelets. extremely rare coagulopathy. Deficiency or low levels of glycoprotein IIb/IIIa (Gp IIb/IIIa), which is a receptor for fibrinogen. As a result --> no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged
● Adhesion ( Bernard-Soulier Syndrome “BSS”) ● Shape change ● Aggregation ( Glanzmann Thrombasthenia ) ● Release ● Clot Retraction
IMP
● Provides information on time course of platelet activation. ● Agonists: ○ ADP ○ Adrenaline ○ Collagen ○ Arachidonic acid ○ Ristocetin ○ Thrombin Reference ranges need to be determined for each agonist.
Bleeding Time Platelet Function Test
Laboratory Testing of Platelet Functions
Platelet Aggregation in (PRP) Platelet rich plasma:
Agonists: ● ADP ● Adrenaline ● Collagen ● Arachidonic acid ● Ristocetin ● Thrombin
Summary
Q6. Why do some malnourished patients bleed excessively when injured? A. Vitamin K deficiency B. Platelet sequestration by fatty liver C. Serum bilirubin raises neutralizing thrombin D. Low serum- protein levels cause factor XIII problems
Q7. Which one of the following would best explain a prolonged bleeding time tests? A. Hemophilia A B. Hemophilia B C. Thrombocytopenia D. Coumarin use
Q8. A teenage boy with numerous nosebleeds was referred to a physician for evaluation prior to a minor surgery. His prothrombin time(PT) was 11 secs (11-15sec normal), partial thromboplastin time(PTT) was 58 secs (25-40sec normal), and bleeding time was 6. min (2-7 min normal). Which of the following is most likely abnormal in this young man? A. Intrinsic pathway B. Extrinsic pathway C. Decreased platelet number D. Defective platelet
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Questions
Q1: Which one would be inhibited by Aspirin to prevent clot formation? A. ADP B. Thromboxane A C. Serotonin D. PGI
Q2: Bernard Soulier Syndrome is caused by: A. A disorder of granules B. A disorder of cytokines C. A disorder of aggregation D. A disorder adhesion
Q3. ADP/ATP can be found in: : A. Dense granules B. OCS C. Alpha granules D. Mitochondria
Q4. Low platelet count can be caused by: A. Hypersplenism B. Splenomegaly C. Hepatomegaly D. A&B
Q5. The coagulation pathway that begins with tissue thromboplastin is: A. Intrinsic pathway B. Extrinsic pathway C. Common pathway D. Fibrin stabilization
Answers1: B2: D3: A4: D5: B6: A7: C8: A
MCQs
