Blood Components and Functions Quiz

Plasma vs Serum

• Plasma is the liquid portion of blood with anticoagulants added
• Serum is the liquid portion of blood after clotting

Blood Vessels

• Arteries carry blood away from the heart
• Arterioles are small arteries
• Veins carry blood towards the heart
• Venules are small veins

Blood Cells

• Erythrocytes (RBC) are red blood cells:
  • Normal range is 4.2-6.1 million per microliter of blood
• Leukocytes (WBC) are white blood cells:
  • Normal range is 5-10 thousand per microliter of blood
• Platelets are cell fragments, involved in blood clotting, also called thrombocytes:
  • Normal range is 250-500 thousand per microliter of blood

Hemostasis

• The process of stopping bleeding from injured blood vessels
• Thrombosis is a pathological process where thrombi (blood clots) prevent blood flow

Coagulation

• The process of turning liquid blood into a gel (blood clot)
• Activation of coagulation factors leads to clot formation
• Inappropriate activation of coagulation factors leads to thrombus formation
• Decreased activation (deactivation) of coagulation factors can lead to excessive bleeding

Anticoagulants

• Substances that prevent coagulation

Anticoagulants in Nature

• Anopheles mosquitos produce thrombin-directed anticoagulants in their saliva
• Culex mosquitos produce Factor Xa-directed anticoagulants in their saliva
• Animals that feed on blood have evolved mechanisms to interfere with blood coagulation of their prey
• Leeches (Hirudo medicinalis) produce:
  • Hirudin: Inhibits thrombin; A recombinant version of hirudin is Lepirudin
  • Antistatin: Inhibits Factor Xa

Why Study Coagulation & Anticoagulants

• Plays a role in thrombosis prevention and treatment
• Treats blood clotting disorders like hemophilia
• Treatments for disseminated intravascular coagulation disorder

Physiology of Coagulation

• Initiated by injury or stasis
• Platelets and coagulation factors are crucial
• Coagulation factors are designated I-XIII
• Activated platelets, fibrin, and red blood cells form a thrombus/clot

Coagulation Factors & Pathways

• Most coagulation factors are plasma glycoproteins
• They are produced by hepatocytes
• They are typically inactive serine proteases in a zymogen form
• The active form is created by proteolytic cleavage of a specific peptide bond
• In the coagulation cascade, an active coagulation factor cleaves and activates its substrate
• The goal of coagulation cascades is to convert soluble fibrinogen to insoluble fibrin
• Extrinsic pathway is activated by tissue factor expression
• Intrinsic pathway is activated by contact of Factor XII with an anionic surface (collagen)

Coagulation Factors & Pathways (2)

• Platelet procoagulant activity is essential for blood clotting
• Platelets provide a phospholipid surface for Ca2+ dependent coagulation complexes
• Thrombin activates platelets to aggregate
• Platelet activation and blood coagulation are inter-dependent events for clot formation

Coagulation Pathways

• Contact Activation Pathway (Intrinsic pathway)
  • Stimulated by factors in the blood
• Tissue Factor Pathway (Extrinsic pathway)
  • Stimulated by factors outside the blood
• Both pathways contribute to clot formation

Clot Formation

• An example of a video that describes hemostasis and clot formation: https://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htm
• An example of a video that describes hemostasis and clot formation: https://www.hopkinsmedicine.org/hematology/Coagulation.swf

Steps Involved in Clot Formation

• Vasoconstriction (triggered by endothelin secretion at site of injury from endothelial cells)
• Platelet adhesion
• Platelet activation
• Platelet aggregation (plug formation)
• Fibrin mesh formation
• Incorporation of red blood cells and additional platelets into the clot

Platelets

• Platelets are cell fragments that arise from megakaryocytes in the bone marrow
• They have a lifespan of around 10 days
• They contain cytoplasm but lack nuclei (anucleated)
• They play essential roles in hemostasis and thrombosis
• The platelet surface contains many glycoproteins (GP) which serve as adhesive receptors for adhesive proteins such as:
  • Fibrinogen
  • Fibronectin
  • Von Willebrand Factor (vWF)

Platelets (2)

• Platelets contain receptors for interaction with physiological stimuli, such as:
  • ADP
  • Thrombin
  • Thromboxane A2 (TXA2)
  • Collagen
  • Epinephrine
• Activated platelets undergo a series of reactions leading to hemostatic plugs and thrombi

Platelet Adhesion, Activation & Aggregation (1)

• Platelets normally do not adhere to shielded/masked subendothelium of a blood vessel
• When a blood vessel is damaged, platelets adhere to the exposed subendothelium
• This initiates their activation processes
• This adhesion is mediated by the platelet membrane glycoproteins:
  • GPVI binds to collagen
  • GPIb binds to Von Willebrand Factor (vWF)
• Vascular injury causes endothelial denudation (loss) and exposes collagen

Platelet Secretion (Release Reaction)

• Activated platelets release contents from their dense granules
• These contents include potent platelet agonists/activators such as:
  • ADP (adenosine diphosphate)
  • Serotonin
• Activated platelets also make TXA2

Platelet Adhesion, Activation & Aggregation

• Activation of other platelets results from binding of ADP and TXA2 to their respective receptors:
  • P2Y1 and P2Y12 are receptors (GPCRs) for ADP
  • Thromboxane A2 (TxA2) is the major product of COX-1 involved in platelet activation through binding to the thromboxane A2 receptor (GPCR)
  • Stimulated by agonists, these receptors activate the fibrinogen-binding glycoprotein GPIIb/IIIa to promote platelet aggregation (platelet-to-platelet interaction)

Platelet Adhesion, Activation & Aggregation

• PAR1 and PAR4 are protease-activated receptors (GPCRs) that are activated by thrombin (clotting factor IIa)
• Stimulated by agonists, these receptors activate the fibrinogen-binding glycoprotein GPIIb/IIIa to promote platelet aggregation (platelet-to-platelet interaction)

Platelet Adhesion, Activation & Aggregation (2)

• The symmetrical fibrinogen molecule will act as a molecular bridge linking the activated platelets together

Platelet Adhesion, Activation & Aggregation (3)

• Prostaglandin I2 (PGI2) synthesized by endothelial cells inhibits platelet activation
• PGI2 binds to its receptor (GPCR) and raises cAMP levels
• cAMP is a platelet inhibitor preventing platelets from aggregating and forming a clot
• Phosphodiesterases are enzymes that degrade or breakdown cAMP reversing its inhibitory effects on platelet activation

Thromboxane A2 Formation by COX

• Cycloxygenase (COX) is an enzyme involved in the formation of thromboxane A2

Platelet Activation by Thromboxane A2

• TXA2 activates platelets by increasing intracellular calcium levels

Platelet Activation

• Scanning electron micrographs are shown for resting platelets, and platelets undergoing activation

Platelet Activation by ADP (Adenosine DiPhosphate) and Thrombin

• ADP activates by lowering cAMP levels and increasing intracellular calcium levels

Clot Formation

• The text indicates √ which could be indicating a visual depiction of clot formation that is missing