(17.5.6) Platelets & Hemostasis

Describe the structure and function of Platelets

• STRUCTURE

  • Cytoplasmic fragments of megakaryocytes

  • Blue-staining outer region; purple granules

  • Normal 150,000-400,000 platelets/ml of blood

• FUNCTION

  • Granules contain serotonin and ADP

  • Form temporary platelet plug that helps seal break in blood vessels

Role of Megakaryocyte

A gigantic cell in the bone marrow that is responsible for forming platelets

How do platelets enter the blood?

Megakaryocytes place platelets in the blood by passing them through the wall of sinusoidal capillaries (with large openings in their walls) in the bone marrow

What chemicals are involved in clotting process?

1. Serotonin

2. Calcium

3. Enzymes

4. ADP

5. Platelet-derived growth factor

T/F: Circulating platelets are kept active 

→ False 

• Circulating platelets are kept inactive and mobile by nitric oxide (NO) and prostacyclin from endothelial cells lining blood vessels

Role of Hemostasis

• Fast series of reactions for stoppage of bleeding

• Prevention of blood loss

List the major steps of Hemostasis 

• Requires clotting factors and substances released by platelets and injured tissues

  1. Vascular spasm

  2. Platelet plug formation

  3. Coagulation (blood clotting)

Explain Step 1 - Vascular spasm

• Vessel responds to injury with vasoconstriction

• Vascular spams are triggered by:

  • Direct injury to vascular smooth muscle

  • Chemicals released by endothelial cells and platelets

  • Pain reflexes

• Strongly constricted artery can significantly reduce blood flow until other mechanisms can kick in

• Most effective in smaller blood vessels

Explain Step 2  - Platelet Plug Formation 

• POSITIVE FEEDBACK CYCLE → as more platelets stick they release more chemicals → which cause more platelets to stick and release more chemicals 

• Aggregating (sticking together), forming a plug that temporarily seals the break in the vessel wall

• Platelet plugs are fine for small vessels tears, but larger breaks in vessel need additional step 

What chemicals are released by Platelets when become activated?

1. Adenosine diphosphate (ADP)

   • Potent aggregating agent that causes more platelets to stick to the area and release their contents

2. Serotonin and Thromboxane

   • Messengers that enhance vascular spasm and platelet aggregation

Explain Step 3  - Coagulation

Hemostasis → fast series of reactions for stoppage of bleeding 

• Reinforces platelet plug with fibrin threads 

  • Blood is transformed from lipid to a gel when dissolved blood proteins assemble into fibrin threads

• Blood clots are effect in sealing larger vessel breaks

Function of Clotting Factors

• FUNCTION → A group of substances, mostly plasma proteins synthesized by the liver, that circulate in blood in an inactive form and work together in series to facilitate the multistep process of blood clotting

  • Procoagulants

  • Numbered I to XII in order of discovery 

  • Vitamin K needed to synthesize four factors

Which Coagulation Factors require Vitamin K? 

1. Factor II → Prothrombin 

2. Factor VII 

3. Factor IX 

4. Factor X

How is Coagulation of blood initiated?

COAGULATION → Pathways to Prothrombin Activator

1. Intrinsic pathway

2. Extrinsic pathway

Explain Phase I of Coagulation

→ Pathway to Prothrombin Activator

• Intrinsic pathway

  • Intrinsic because the factors needed for clotting are present within (intrinsic to) the blood

  • Vessel endothelium ruptures, exposing underlying tissue

  • Platelet cling and their surfaces provide sites for mobilization of factors 

  • Phospholipid surfaces of aggregated platelets 

• Extrinsic pathway

  • Extrinsic because the tissue factor it requires is outside of blood

  • Tissue cell trauma expose blood to → Tissue factor TF 

• BOTH

  • Platelet phospholipid membranes

  • Pathways converge as prothrombin is converted to thrombin

Explain Phase II of Coagulation 

→ Pathway to thrombin

• Prothrombin activator catalyzes transformation of prothrombin to active enzyme thrombin 

Explain Phase III of Coagulation 

→ Pathway to Fibrin Mesh

1. Thrombin catalyzes the transformation of the soluble clotting factor fibrinogen into fibrin

2. Fibrin molecules polymerize (join together) to form long, hairlike, insoluble fibrin strands

3. Fibrin mesh that traps blood cells (platetes) and effectively seals the hole until the blood vessel can be permanently repaired

What prevents fibrin from forming a mesh in a healthy, unbroken blood vessel?

When thrombin is not bound to fibrin, it is inactivated by antithrombin.

Summarize Blood Clotting Process

1. Vascular Spasm

   • The injured blood vessel constricts to reduce blood flow to the site of the injury.

2. Platelet Plug Formation

   • Platelets are attracted to the injury, where they stick together and form a temporary plug, with the help of von Willebrand factor

3. Coagulation Cascade Activation

   • This is a series of reactions involving clotting factors, which are proteins that circulate in the blood in an inactive form

     • Phase I Extrinsic or intrinsic pathway → both of which converge into a common pathway of Formation of Prothrombin activator

     • Phase II → Prothrombin activator catalyzes the conversion of a plasma protein called prothrombin into the active enzyme thrombin

     • Phase III → Thrombin catalyzes the transformation of the soluble clotting factor fibrinogen into fibrin

       • Fibrin molecules polymerize (join together) to form long, hairlike, insoluble fibrin strands

       • Fibrin mesh that traps blood cells and effectively seals the hole until the blood vessel can be permanently repaired

Role of Anticoagulants

• Factors that normally dominate in blood to INHBIT coagulation

  • Endothelial cells secrete antithrombin substances such as nitric oxide and prostacyclin

  • Vitamin E quinone, formed when vitamin E reacts with O2, it a potent anticoagulant

Explain Regulation of Coagulation

• Limited amount of thrombin is restricted to clot by fibrin threads → preventing clot from getting too big or escaping into blood stream

  • Antithrombin III → inactivates any inbound thrombin that escapes into bloodstream

  • Heparin → in basophil and mast cells inhibits thrombin by enhancing Antithrombin III

What enzyme removes unneeded clots after healing has occurred?

→ Plasmin

Explain what happens to Clots after Hemostasis?

1. Fibrinolysis → Process whereby clots are removed after repair is completed

   • Begins within 2 days and continues for several days until clot is dissolved

2. Plasminogen → plasma protein that is trapped in clot, is converted to plasmin, a fibrin-digesting enzyme

List two major types of Hemostasis Disorders 

1. Thromboembolic disorder 

   • Result in undesirable clot formation

2. Bleeding disorders 

   • Abnormalities that prevents normal clot formation

List Thrombembolic Disorders 

1. Thrombus

2. Embolus 

3. Embolism

Compare and Constrast Thromboembolic Disorders

1. Thrombus

   • Clot that develops and persists in unbroken blood vessel

   • Risk factors → May block circulation, leading to tissue death

2. Embolus 

   • Thrombus freely floating in bloodstream 

3. Embolism

   •  Embolus obstructing a vessel (pulmonary or cerebral emboli) 

   • Risk factors → atherosclerosis, inflammation, slowly flowing blood or blood stasis for immobility 

Role of Anticoagulant Drugs and Examples 

• Used to prevent undesirable clotting 

  1. Aspirin

  2. Heparin

  3. Warfarin (Coumadin)

Describe how Heparin works

Anticoagulant used clinically for pre- and post-operative cardiac care

Describe how Watfarin works

• Used for people prone to atrial fibrillation

• Interferes with actions of vitamin K  

List Bleeding Disorders 

1. Thrombocytopenia

2. Impaired liver function

3. Hemophilia

Describe Causes and Treatment of Thrombocytopenia

Bleeding Disorder

• Deficient number of circulating platelets 

  • Petechiae appear as a result of spontaneous, widespread hemorrhage

  • Platelet count <50,000/uL is dx

• TREAMTNET

  • Transfusion of concentrated platelets

Describe Causes of Impaired Liver Function 

Bleeding Disorder

• Inability to synthesize procoagulants (clotting factors) 

• CAUSES 

  • Vitamin K deficiency 

  • Hepatitis

  • Cirrhosis

  • Liver disease - prevent liver from producing bile, which is needed to absorb fat and vitamin L

Describe Causes of Hemophilia  

Bleeding Disorder

• Includes several similar hereditary bleeding disorders 

  • Hemophilia A → most common type (77% of all cases) due to factor VIII deficiency

• SYMPTOMS:

  • Prolonged bleeding, especially into joint cavities