A&P of Blood Cells - Platelets

What are antigens on red blood cells?

Antigen are surface markers: specific molecules, often glycoproteins or glycolipids, that are present on the cell membrane

• play a key role in blood type determination and immune responses.

What is the human ABO blood group?

Determines blood types A, B, AB, and O based on the presence or absence of A and B antigens

• A Blood - Has A antigens

  • Have Group B Antibodies

• B Blood - Has B antigens

  • Has Group A Antibodies

• AB Blood - Has A & B antigens

  • None

• O Blood - None

  • Antibodies against A & B

What are natural isoantibodies?

• Produced in absence of immune reaction

• Inherently present within the body

What are immune antibodies?

• Antibodies produced after being exposed to foreign cell/antigens

Domestic animals like _____, ____, ____ and ____ have different ____ _____ BUT they do not have different ______ against the _____.

horse, cattle, sheep, pigs

blood isoantigens

antibodies, antigens

• Therefore there is no immune reaction.

Why might the first un-matched blood transfusion in an animal be okay, but not subsequent transfusions?

Some animals do not have naturally occurring isoantibodies

A first transfusion may not lead to an immediate reaction, subsequent transfusions can carry a higher risk of complications due to sensitization

• Animal will build antibodies to that blood

What is notable about the blood grouping system in cats?

• Cats express naturally occurring isoantibodies

• A, B, AB blood grouping

• Type B Cats - have anti A antibodies

• Type A - have low concentration of anti B antibodies

  • Not as significant

Meaning unmatched transfusions result in significant numbers of transfusion reactions

• Can depend on breed as well

If we perform repeated transfusions, we might see _______ ______ due to the immune mediated ______ _____.

transfusion reactions, antibody production

What is notable about the blood grouping system in dogs?

Dog Erythrocyte Antigen (DEA 1-8)

• 63% of dogs are DEA 1.1 positive, naturally occurring antibodies are rare so unmatched 1st transfusion is usually okay

• However some variations are highly antigenic, so if unmatched transfusions are used, significant antibody production is stimulated, animals may react to transfusion if treated with similar cells the second time

What is haemostasis?

spontaneous arrest of bleeding from a ruptured vessel

What three main physiological processes occur in haemostasis?

• Vascular Response

• Platelet Plug Formation

• Coagulation to form clot

What occurs in the vascular response?

• Damage to epithelium —> releases factors causing constriction of smooth muscle

• Maintained constriction by substances released from endothelium and platelets

Is a temporary, short-term response

What occurs in the platelet plug formation?

• Vascular Injury: When a blood vessel is injured, the endothelial cells are disrupted, exposing the underlying collagen

• Exposure of Collagen: The exposure of collagen to the bloodstream initiates the process of hemostasis.

• Platelet Activation: Platelets adhere to the exposed collagen through von Willebrand factor (vWF), which acts as a bridge. This adhesion activates the platelets.

• Arachidonic Acid Pathway: Upon activation, platelets release arachidonic acid from their membrane phospholipids. Arachidonic acid is then converted into thromboxane A2

• Thromboxane A2 Function: TXA2 further activates platelets and promotes their aggregation.

• Aggregation: Platelets stick to one another and to the von Willebrand factor, forming a larger and more stable platelet plug.

• Role of Prostacyclin and Prostaglandin I: To limit the extent of the platelet plug to areas of damage, the endothelial cells produce prostacyclin (PGI2) and prostaglandin I2, which are potent inhibitors of platelet aggregation. These molecules counteract the effects of thromboxane A2, ensuring that platelet activation and aggregation are restricted to the site of injury.

The coagulation pathway can be separated into what two pathways?

What is the basis of each?

• Intrinsic Pathways

  • Involves several clotting factors present in the blood (Factors XII, XI, IX, and VIII). It is considered a complex pathway due to the number of factors involved

  • Triggers a cascade of reactions

  • Takes longer to initiate

• Extrinsic Pathways

  • activated by external trauma to the blood vessel, specifically the exposure of tissue factor (TF) from damaged tissues

  • Primarily involves Factor VII

  • Acts more quickly and is more direct

What is are the steps in the final, common coagulation pathway?

• Conversion of Prothrombin to Thrombin:

• Thrombin Action:

  • Conversion of Fibrinogen to loose Fibrin: Thrombin catalyzes the conversion of fibrinogen (soluble) into fibrin (insoluble).

  • Activation of Factor XIII: Thrombin also activates Factor XIII, which cross-links fibrin strands to stabilize the clot, forming stabilized fibrin

• Formation of the Fibrin Mesh: The fibrin strands weave through the platelet plug, creating a stable fibrin mesh net that solidifies the clot

• Clot Retraction: Platelets within the clot contract, pulling the edges of the wound together, which aids in healing

Describe the anticlotting mechanisms.

• Mention PGI2

• Mention Activated Protein C

• Mention antithrombin III with heparin

• PGI2

  • PGI2 prevents platelets from sticking together

• Activated Protein C

  • Thrombin activates Protein C activator which activates Protein C which inhibits Factors VIII and V

  • Leading to less Thrombin for Fibrinogen/Fibrin

• Thrombin

  • Thrombin is a key enzyme that converts fibrinogen into fibrin and activates platelets.

• Antithrombin III with Heparin

  • When ATIII is active, it reduces thrombin levels, further preventing clot formation.

Dissolution of the blood clot depends on what two processes?

• Clot Retraction

• Fibrinolysis

How does the process of fibrinolysis occur?

• The clotting cascade leads to the formation of thrombin, which converts fibrinogen to fibrin, creating a stable clot.

• When healing occurs, endothelial cells secrete t-PA, which activates plasminogen to plasmin.

  • In order for t-PA to activate however, fibrin must assist, binding enhances its activity

    • Plasmin: Plasmin is an enzyme that digests fibrin, breaking down the fibrin mesh into smaller fragments known as soluble fibrin fragments.

• Plasmin then breaks down the fibrin clot into soluble fragments, completing the fibrinolysis process.

What is urokinase?

• Tissue type plasminogen activator

• Converts plasminogen to plasmin, does not bind to fibrin like t-PA

What is tPA?

tissue plasminogen activator

What are some anti-clotting drugs/agents?

Aspirin

• Inhibits COX and thus inhibits thromboxane A2 production, thus reducing platelet aggregation and coagulation

Coumarin Derivatives

• Affects production of vitamin K dependent clotting factors within the liver:

  • e.g. dicumarol, warfarin

Heparin

• Natural cofactor for antithrombin III

Ca2+ chelating agents - citrate, oxalate, fluoride salts, EDTA

What are some diagnostic tests we can perform to determine the abnormalities of haemostasis?

Bleeding Time

• Time to form primary plug after stab or incision

• Screening test for vascular and platelet disorders

Whole Blood Clotting Time

• Time taken for 1ml of blood to clot

• Detect severe deficiencies of one or more intrinsic coagulation factors

One Stage Prothrombin Test

• Plasma incubated with tissue thromboplastin and clotting initiated by the addition of Ca2+

• Principal test for extrinsic and common pathway defects

Activated Partial Prothrombin Test (Kaolin cephalin clotting test)

• Plasma is activated under controlled conditions in the presence of phospholipid and clotting is activated by Ca2+

• Used to detect intrinsic and common pathway defects

What are some common blood disorders in dogs?

• Von Willebrands Disease

  • Common inherited bleeding disorder in dogs

• Factor VIII Deficiency - Haemophilia

  • Factor VIII deficiency causing intrinsic coagulation pathways to be affected

• Factor IX Deficiency - Haemophilia B

  • Factor IX deficiency, affection coagulation pathways

Causes excessive bleeding, hematomas, internal bleeding, etc.