Platelets Production and Functions
Introduction to Platelets
Platelets, also known as thrombocytes, are small, anucleate cell fragments that play a crucial role in hemostasis and thrombosis. They are derived from megakaryocytes in the bone marrow and circulate in the blood for 7-10 days before being removed by the reticuloendothelial system. Platelets are essential for maintaining vascular integrity and initiating the coagulation cascade in response to vessel injury.
Key facts about platelets:
- Normal platelet count: 150,000 - 450,000 per microliter of blood
- Size: 2-3 μm in diameter
- Lifespan: 7-10 days
- Production site: Bone marrow
Platelet Production (Thrombopoiesis)
Platelet production, or thrombopoiesis, is a complex process that occurs in the bone marrow. The main steps include:
- Megakaryocyte differentiation: Hematopoietic stem cells differentiate into megakaryocyte progenitors under the influence of various growth factors, primarily thrombopoietin (TPO).
- Megakaryocyte maturation: Megakaryocytes undergo endomitosis, resulting in polyploid cells with multilobed nuclei and increased cytoplasmic volume.
- Platelet formation: Mature megakaryocytes extend long cytoplasmic processes called proplatelets into sinusoidal blood vessels. These proplatelets fragment to release individual platelets into the circulation.
- Regulation: Thrombopoietin is the primary regulator of platelet production. It is produced mainly by the liver and kidneys and acts on megakaryocytes and their precursors to stimulate proliferation and maturation.
Other factors influencing platelet production include interleukin-6 (IL-6), interleukin-11 (IL-11), and stem cell factor (SCF).
Platelet Structure
Platelets have a complex structure that enables their various functions. Key structural components include:
- Plasma membrane: Contains numerous glycoprotein receptors crucial for platelet adhesion and activation.
- Open canalicular system (OCS): An extensive network of internal membranes that increases surface area and serves as a conduit for the release of granule contents.
- Dense tubular system: A smooth endoplasmic reticulum that stores and releases calcium.
- Cytoskeleton: Composed of actin, myosin, and microtubules, allowing shape change and pseudopod formation.
- Granules: Storage organelles containing various bioactive molecules:
- α-granules: Contain proteins such as fibrinogen, von Willebrand factor, and platelet factor 4.
- Dense granules: Store small molecules like ADP, ATP, serotonin, and calcium.
- Lysosomes: Contain hydrolytic enzymes.
- Mitochondria: Provide energy for platelet functions.
Platelet Functions
Platelets perform several critical functions in hemostasis and beyond:
- Adhesion: Following vessel injury, platelets adhere to exposed subendothelial collagen via glycoprotein VI and integrin α2β1. Von Willebrand factor (vWF) mediates initial platelet tethering, especially under high shear conditions.
- Activation: Adherent platelets become activated by various agonists (e.g., collagen, thrombin, ADP). This leads to:
- Shape change and pseudopod formation
- Granule secretion
- Integrin activation (especially αIIbβ3)
- Phosphatidylserine exposure on the outer membrane leaflet
- Aggregation: Activated platelets aggregate via fibrinogen bridges between αIIbβ3 integrins on adjacent platelets.
- Procoagulant activity: Activated platelets provide a phosphatidylserine-rich surface for the assembly of coagulation factor complexes, accelerating thrombin generation.
- Clot retraction: Platelet contraction helps to consolidate and stabilize the formed thrombus.
- Wound healing: Platelets release growth factors (e.g., PDGF, TGF-β) that promote tissue repair and angiogenesis.
- Inflammation and immunity: Platelets interact with leukocytes and release inflammatory mediators, contributing to innate immune responses.
Platelet Disorders
Platelet disorders can be quantitative (abnormal platelet count) or qualitative (abnormal platelet function):
Quantitative Disorders:
- Thrombocytopenia (low platelet count):
- Immune thrombocytopenia (ITP)
- Drug-induced thrombocytopenia
- Heparin-induced thrombocytopenia (HIT)
- Thrombotic thrombocytopenic purpura (TTP)
- Disseminated intravascular coagulation (DIC)
- Thrombocytosis (high platelet count):
- Reactive thrombocytosis
- Essential thrombocythemia
Qualitative Disorders:
- Inherited disorders:
- Bernard-Soulier syndrome
- Glanzmann thrombasthenia
- Storage pool deficiencies
- Acquired disorders:
- Uremia
- Antiplatelet drugs (e.g., aspirin, clopidogrel)
Platelets Production and Functions
- QUESTION: What is the primary site of platelet production in the body?
ANSWER: Bone marrow - QUESTION: Which cells in the bone marrow are responsible for platelet production?
ANSWER: Megakaryocytes - QUESTION: What is the average lifespan of a platelet in circulation?
ANSWER: 7-10 days - QUESTION: Which hormone is the primary regulator of platelet production?
ANSWER: Thrombopoietin - QUESTION: What is the normal platelet count range in children?
ANSWER: 150,000-450,000/µL - QUESTION: Which of the following is NOT a primary function of platelets?
ANSWER: Oxygen transport - QUESTION: What is the first step in platelet activation during hemostasis?
ANSWER: Adhesion to exposed collagen - QUESTION: Which platelet receptor is responsible for binding to von Willebrand factor?
ANSWER: Glycoprotein Ib-IX-V complex - QUESTION: What is the term for the shape change that occurs in activated platelets?
ANSWER: Platelet spreading - QUESTION: Which of the following is NOT typically stored in platelet α-granules?
ANSWER: Serotonin - QUESTION: What is the primary function of platelet dense granules?
ANSWER: Storage and release of small molecules like ADP and calcium - QUESTION: Which of the following is a key mediator of platelet aggregation?
ANSWER: Fibrinogen - QUESTION: What is the role of thromboxane A2 in platelet function?
ANSWER: Promotion of platelet aggregation and vasoconstriction - QUESTION: Which platelet receptor is the target of aspirin's antiplatelet effect?
ANSWER: Cyclooxygenase-1 (COX-1) - QUESTION: What is the primary mechanism of action of clopidogrel in inhibiting platelet function?
ANSWER: Blocking the P2Y12 ADP receptor - QUESTION: Which of the following is NOT a typical feature of platelet activation?
ANSWER: Decreased calcium influx - QUESTION: What is the role of platelets in wound healing?
ANSWER: Release of growth factors that promote tissue repair - QUESTION: Which of the following conditions is associated with increased platelet production?
ANSWER: Essential thrombocythemia - QUESTION: What is the term for the release of platelet contents during activation?
ANSWER: Platelet degranulation - QUESTION: Which of the following is NOT a component of the platelet cytoskeleton?
ANSWER: Keratin - QUESTION: What is the role of P-selectin in platelet function?
ANSWER: Mediating platelet-leukocyte interactions - QUESTION: Which stage of megakaryocyte development involves nuclear polyploidization?
ANSWER: Endomitosis - QUESTION: What is the primary site of platelet clearance from circulation?
ANSWER: Liver and spleen - QUESTION: Which of the following is NOT a typical marker of platelet activation?
ANSWER: Decreased surface CD62P expression - QUESTION: What is the role of platelet factor 4 (PF4) in platelet function?
ANSWER: Neutralization of heparin and promotion of platelet aggregation - QUESTION: Which platelet receptor is involved in collagen-induced activation?
ANSWER: Glycoprotein VI - QUESTION: What is the primary function of platelet microparticles?
ANSWER: Promotion of coagulation and intercellular communication - QUESTION: Which of the following is NOT a typical feature of reticulated platelets?
ANSWER: Decreased RNA content - QUESTION: What is the role of CD40 ligand in platelet function?
ANSWER: Mediating platelet-endothelial cell interactions and inflammation - QUESTION: Which of the following conditions is associated with increased platelet turnover?
ANSWER: Immune thrombocytopenia (ITP)
