Introduction to Hemostasis and Platelet Function

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333 Terms

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Hemostasis

A series of cellular and humoral systems balancing blood flow within circulation; the cessation of bleeding.

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Vasoconstriction

Blood vessels constrict to reduce blood flow.

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Platelet Activation

Platelets adhere, aggregate, and secrete granules to form a platelet plug.

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Coagulation Enzyme Activation

Plasma enzymes interact to form an insoluble fibrin clot.

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Fibrinolysis

Plasmin digests fibrin to remove clots and prevent blockage.

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Thrombosis

Formation of a clot in a blood vessel; a thrombus.

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Emboli

Foreign objects like clots or air bubbles causing blockages.

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Coagulation

Sequential interaction of plasma enzymes, cofactors, and related substances forming a fibrin clot.

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Fibrinogen

Plasma protein converted to fibrin (active form), which acts as a 'glue' to stop bleeding.

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Platelets

Smallest blood elements, essential for stopping bleeding and forming plugs.

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Coagulation Factors

Enzymes (procoagulants) responsible for blood clotting.

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Primary Hemostasis

Process: Platelet plug formation.

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Secondary Hemostasis

Process: Fibrin clot formation via enzymatic reactions.

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Key Mediators of Primary Hemostasis

Blood vessels, platelets.

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Key Mediators of Secondary Hemostasis

Coagulation factors.

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End Result of Primary Hemostasis

Platelet plug.

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End Result of Secondary Hemostasis

Insoluble fibrin clot.

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Response of Primary Hemostasis

Initial, rapid, and short-lived.

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Response of Secondary Hemostasis

Delayed but long-term.

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General Process of Hemostasis

Involves vasoconstriction, platelet plug formation, coagulation cascade, clot formation, and fibrinolysis.

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Extravascular Components

Tissues surrounding vessels provide back pressure and trap escaping blood.

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Vascular Components

Blood vessels regulate flow and maintain balance with anti-thrombotic, procoagulant, and fibrinolytic properties.

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Intravascular Components

Platelets and coagulation factors within the blood actively participate in hemostasis.

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Platelet Activation and Aggregation

Involves adhesion, aggregation, and release of substances promoting hemostasis.

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Coagulation Cascade

Involves primary hemostasis (temporary platelet plug) and secondary hemostasis (stabilization with fibrin).

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Key Factors in Coagulation Cascade

Tissue Factor activates the extrinsic pathway; Thrombin converts fibrinogen to fibrin; Factor XIII stabilizes the fibrin clot.

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Fibrinolysis Mechanism

Plasminogen is activated to plasmin, which digests fibrin.

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Significance of Fibrinolysis

Prevents clot persistence, which could cause blockages like strokes.

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Thrombus Formation

Clot formed at the injury site.

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Antithrombotic Actions

Include Tissue Plasminogen Activator (t-PA) initiating fibrinolysis and Thrombomodulin blocking the coagulation cascade.

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Tunica Intima

Inner layer of blood vessels composed of endothelial cells that produce anti-thrombotic substances and anticoagulants.

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Tunica Media

Middle layer of blood vessels composed of smooth muscle that regulates vasoconstriction.

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Tunica Adventitia

Outer layer of blood vessels that provides structural support and is composed of fibroblasts that produce collagen and tissue factor.

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Platelets

Cell fragments that aggregate to form a temporary plug and release granules like ADP, serotonin, and thromboxane A2.

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Coagulation Factors

Proteins that act sequentially to stabilize the platelet plug by forming a fibrin clot.

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Fibrinolytic System

System that breaks down the fibrin clot once healing is complete.

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Normal Hemostatic Balance

Dynamic equilibrium between procoagulants and anticoagulants that prevents unnecessary clotting.

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Anticoagulants

Substances that prevent unnecessary clotting, such as antithrombin and Protein C/S.

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Procoagulants

Substances that facilitate clot formation when needed, such as tissue factor and coagulation factors.

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Endothelial Role

In resting state, produces antithrombotic substances; in activated state, releases tissue factor and von Willebrand factor to initiate clotting.

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Vasoconstriction

Immediate narrowing of blood vessels to minimize blood loss, enhanced by chemical mediators from platelets.

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Platelet Activation

Process involving adhesion, shape change, aggregation, and release reaction of platelets.

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Platelet Plug Formation

Formation of a temporary seal at the site of vascular injury by aggregated platelets.

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Fibrin Clot Formation

Process where the coagulation cascade generates thrombin, converting fibrinogen to fibrin, which reinforces the platelet plug.

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Fibrin Stabilization

Cross-linking of fibrin by Factor XIIIa to stabilize the clot.

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Clot Dissolution (Fibrinolysis)

Process where plasminogen is converted to plasmin, which degrades fibrin into soluble fragments, restoring normal blood flow.

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Bleeding Disorders

Conditions resulting from deficiencies in platelets, coagulation factors, or fibrinolysis inhibitors.

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Thrombotic Disorders

Conditions characterized by excessive clot formation, such as deep vein thrombosis or stroke.

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Therapeutic Interventions

Treatments including anticoagulants, platelet inhibitors, and fibrinolytics to manage clotting disorders.

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Primary Hemostasis

The process of forming a temporary plug to seal injuries in blood vessels, primarily involving platelets.

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Platelet Characteristics

Platelets are discoid-shaped, 2-4 µm in diameter, with a mean platelet volume (MPV) of 8-10 fL.

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Normal Count of Platelets

Normal platelet count ranges from 150-400 × 10^9/L, with some sources stating up to 450 × 10^9/L.

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Lifespan of Platelets

Platelets have a lifespan of 8-11 days, with 9-12 days in circulation.

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Megakaryocytopoiesis

The process of platelet production occurring in the bone marrow by large, multinucleated cells called megakaryocytes.

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Thrombopoietin (TPO)

A hormone primarily produced by the liver that stimulates platelet production, with its plasma concentration inversely proportional to platelet and megakaryocyte mass.

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Megakaryoblast

Early stage of megakaryocyte development.

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Promegakaryocyte

Intermediate stage.

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Megakaryocyte

Large, multinucleated cell responsible for platelet production.

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Metamegakaryocyte

Final stage before platelet release.

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Endomitosis

Megakaryocytes undergo endomitosis (mitosis without telophase), resulting in a multilobulated nucleus.

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Thrombocytopoiesis

Platelets are formed from the megakaryocyte cytoplasm. Proplatelet processes extend into the venous sinuses of the bone marrow, where platelets are shed.

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Platelet Release

A single megakaryocyte can shed 2000-4000 platelets.

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Thrombopoietin (TPO)

Produced by the liver, inversely proportional to megakaryocyte and platelet mass.

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Meg-CSF

Works synergistically with TPO to induce differentiation.

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IL-3

Works synergistically with TPO to induce differentiation.

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BFU-Meg

Least mature progenitor, participates in normal mitosis.

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CFU-Meg

Intermediate stage.

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LD-CFU-Meg

Initiates endomitosis (DNA replication without cytokinesis).

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RUNX1 Transcription Factor

Mediates transition from mitosis to endomitosis.

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NF-E2

Promotes DNA replication, leading to increased ploidy (e.g., 8N → 16N → 32N).

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128N Ploidy

Associated with hematologic disease.

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MK-I (Megakaryoblast)

Size: 14-18 μm. Features: Round nucleus, high nucleus-to-cytoplasm ratio (3:1), basophilic cytoplasm, no visible granules.

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MK-II (Promegakaryocyte)

Size: 15-40 μm. Features: Indented nucleus, abundant cytoplasm, few azurophilic granules.

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MK-III (Megakaryocyte)

Size: 30-50 μm. Features: Lobulated nucleus, basophilic chromatin, visible DMS.

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Demarcation System (DMS)

Serves as 'platelet territories,' defining individual platelets.

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Reticulated Platelets ('Stress Platelets')

Larger than normal platelets, diameter > 6 μm. MPV (Mean Platelet Volume): 12-14 fL.

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RUNX1

Mediates transition to endomitosis, inhibiting the Rho/ROCK pathway.

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NF-E2

Promotes DNA replication and increased ploidy.

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FOG-1 and GATA-1

Regulate megakaryocyte differentiation and maturation.

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MK-I (Megakaryoblast)

14-18 μm, round nucleus, not visible granules, no shedding, high nucleus-to-cytoplasm ratio (3:1), basophilic cytoplasm.

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MK-II (Promegakaryocyte)

15-40 μm, indented nucleus, few azurophilic granules, developing abundant cytoplasm, no shedding, visible and defined granules.

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MK-III (Megakaryocyte)

30-50 μm, lobulated nucleus, basophilic chromatin, azurophilic, alpha, and dense granules.

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Peripheral Zone (Outer Zone)

Facilitates platelet attachment to injury site and aggregation for plug formation, maintains negative surface charge to prevent unwanted platelet activation.

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Glycocalyx

Adhesive layer made of mucopolysaccharides, contains glycoproteins that interact with thrombin, von Willebrand factor (vWF), and fibrinogen.

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Gp Ib/IX/V

Receptors for vWF, essential for adhesion.

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Gp IIb/IIIa

Binding sites for fibrinogen, necessary for aggregation.

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Phospholipid Bilayer

Selectively permeable membrane structure of the plasma membrane.

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Phosphatidylinositol

Precursor for arachidonic acid (thromboxane A2 production).

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Phosphatidylserine

Flips to outer leaflet during activation, enhancing platelet activation.

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Cholesterol

Maintains membrane fluidity.

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Structural Zone (Sol-Gel Zone)

Provides structural support, shape change, and contractility.

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Microfilaments

Components include actin, which is contractile and anchors glycoproteins and proteoglycans, and myosin, which facilitates contraction.

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Thrombosthenin

Actomyosin complex responsible for clot retraction.

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Organelle Zone

Facilitates secretion of cellular contents.

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Alpha Granules

Store proteins like platelet-derived growth factor (PDGF), fibronectin, vWF, fibrinogen, factor V, etc., and are the most numerous granules (50-80 per platelet).

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Dense Granules

Contain small molecules (calcium, ADP, ATP, serotonin, etc.) critical for aggregation, with 2-7 per platelet.

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Mitochondria

Site for ATP synthesis and glycogen metabolism.

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Surface-Connected Canalicular System (SCCS)

Invagination of the plasma membrane, enhancing platelet interaction with the environment, and route for endocytosis and secretion of alpha granules.

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Dense Tubular System (DTS)

Condensed rough endoplasmic reticulum remnant that sequesters calcium and contains enzymes (phospholipase A2, cyclooxygenase, thromboxane synthase), controlling platelet activation and prostaglandin synthesis.

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Alpha Granules

Most numerous granules in platelets, with 50-80 granules per platelet, filled with proteins including coagulation proteins like Factor V, Factor VIII, fibrinogen, and vWF.