Platelets and Coagulation

What are platelets

• not cells, but small fragments of marrow cells called megakaryocytes

What is the simple process of platelet formation

myeloid stem cell → megakaryoblast → megakaryocyte → platelets

What is Hemostasis?

• cessation of bleeding

What are some functions of platelets

• secrete vasoconstrictors

• form platelet plugs

• secrete procoagulants

• initiate formation of a clot dissolving enzyme

• secrete chemicals that attract neutrophils and monocytes to sites of inflammation

• internalize and destroy bacteria

• secrete growth factors that simulate mitosis in fibroblast

What is thrombopoiesis

• production of platelets

• stimulated by thrombopoietin

What are the different mechanisms in hemostasis?

• vascular spasm

• platelet plug

• coagulation

What is a vascular spasm?

• most immediate production against blood loss that constricts a broken vessel

What is prostacyclin and what is its function?

• platelet repellent that coats endothelium

• prevents platelet acticulation when there is no damage

What occurs platelet plug formation?

• broken vessel exposes collagen fibers to blood

• this causes platelets to grow long spiny pseudopods that adhere to the vessel and to other platelets

• mass of platelets creates a plug

What is the main function of coagulation?

• last but most effective defense against bleeding

• main objective is to convert fibrinogen into fibrin

  • a sticky protein that adheres to the walls of a vessel

What is the extrinsic mechanism?

• initiated by clotting factors released by the damaged blood vessel and perivascular tissues

• factors come from sources that are EXTERNAL to blood itself

What is the Intrinsic Mechanism

• uses only clotting factors found in the blood itself

What are clotting factors?

• procoagulants

• always present in plasma in an inactive form

• once one is activated, it functions as an enzyme that activates the next one in the pathway

What are the steps in the extrinsic mechanism?

1. thromboplastin (factor III) forms a complex with VII

2. in the presence of Ca2+ it activates factor X

What are the steps in the intrinsic mechanism?

1. platelets degranulate and release factor XII

2. cascade of reactions leads to activated factors XI, IX, and VIII in that order

3. each serves as enzyme that catalyzes next step

4. presence of Ca2+ and PF3 is needed

5. finally leads to factor X

What are the steps in the common pathway?

1. factor X combines with factor III

2. in presence of Ca2+ and PF3, prothrombin activator is produced

3. this acts on prothrombin (factor II) and converts it to thrombin

4. thrombin converts fibrinogen to fibrin monomer

5. monomers covalently bond to form fibrin polymer

6. facto XIII cross links strands to form blood clot

How does the positive feedback mechanism work in coagulation?

• thrombin works with factor V to accelerate production of prothrombin activator

• this produces more thrombin

How does coagulation work as an amplification mechanism?

• each activated enzyme in the pathway produces a larger number of enzyme molecules at the following step

What is clot retraction?

• spinous pseudopods of platelets adhere to fibrin strands and contract

• this pulls on fibrin threads and draws edges of broken vessels together

What is fibrinolysis?

• dissolution of a clot

• achieved by a small cascade of reactions with a positive feedback component

How does the positive feedback mechanism in fibrinolysis work?

• thrombin also activates plasmin

• plasmin indirectly promotes the formation of more kallikrein

What are the steps in fibrinolysis?

• factor XII catalyzes the formation of plasma enzyme kallikrein

• kallikrein converts inactive protein plasminogen into plasmin

• plasmin breaks up fibrin polymer

Adenosine diphosphate (ADP)

• stimulates platelet aggregation and secretion

Platelet Factors

• proteins that play a role in clotting

Thromboxane A2

• platelet aggregation and activation

• vasoconstriction

Calcium ions

• required for platelet aggregation and clotting process

Prostagaids

• aid in vasoconstriction/ platelet clotting

Arrows of the Intrinsic Pathway

platelet degradation → Factor XI → Factor XI → Factor IX plus Ca2+ and PF3 → Factor VIII IX complex → Factor X

Arrows of Extrinsic Pathway

damaged tissue → factor III (thromboplastin) → factor III factor VII complex with Ca2+ → factor X

Arrows of common pathway

factor X → combines with factor III and V when with Ca2+ and PF3 → prothrombin activator → thrombin → fibrinogen → fibrin monomer → Factor XIII crosslinks strands to create blood clot

Arrows for Fibrinolysis

Factor XII → activates kallikrein → cleaves plasminogen → plasmin → dissolves clot → takes fibrin polymer and degrades it

Serotonin Function

• release will cause vasoconstriction by activating vascular smooth muscle

von Willebrand Factor

• glycoprotein that promotes adhesion (platelet + collagen)

Prostaglandins and Phospholipids function

• further aid with vasoconstriction

• positive clotting proteins

Platelet Activation Factors

• released by monocytes/macrophages

• enhance clotting

Factor III (Tissue Factor)

• membrane bound glycoprotein

• found in tunica media and adventitia

Adventitia

• procoagulant activated when exposed to blood

Factor XII

• plasma protein synthesized by the liver

• activated when exposed to collagen fibers in connective tissue