Hematology: Blood Coagulation

Hemostasis/Coagulation

• Hemostasis is the process that stops bleeding from damaged blood vessels
• Blood vessels are channels that distribute blood to body tissue
• Blood vessels comprise two closed systems of tubes starting and ending at the heart
• Pulmonary vessels transport blood from the right ventricle to the lungs, and back to the left atrium
• Systemic vessels carry blood from the left ventricle to the body tissues and return it to the right atrium
• Blood vessels are classified as arteries, capillaries, or veins based on structure and function

Arteries

• Arteries carry blood away from the heart
• Pulmonary arteries transport low oxygen blood from the right ventricle to the lungs
• Systemic arteries transport oxygenated blood from the left ventricle to body tissues

Artery Wall

• Artery walls have three layers: tunica externa, tunica media, and tunica intima
• Tunica intima consists of an inner layer of endothelial cells and a basement membrane
• Tunica media composed of smooth muscle and elastic fibers
• Tunica externa made up of connective tissue

Veins

• Veins carry blood toward the heart
• Pulmonary veins carry high oxygen blood from the lungs to the left atrium
• Systemic veins carry low oxygen blood from the body tissues to the right atrium

Vein Wall

• Vein walls also have three layers: tunica externa, tunica media, and tunica intima
• The layers are thinner than those in arteries
• There is less smooth muscle, compared to arteries

Capillaries

• Capillaries are the smallest and most numerous blood vessels, forming connections between arteries and veins
• Their primary function is material exchange between blood and tissue cells

Endothelial Cell Function and Platelet Activation

• Healthy endothelial cells produce antiplatelet and anticoagulant agents that prevent platelet aggregation and fibrin formation
• In response to dysfunctional endothelium, endothelial cells trigger fibrin formation and platelet adhesion/aggregation

Structure of Platelets

• Platelets contain surface-containing tubules, microtubules, dense granules, alpha granules, glycogen, mitochondria, and dense granules

Platelet Granules

• Platelets have three main granule types
  • Alpha granules are abundant in platelets, and are rapidly exocytosed upon activation to enhance hemostasis and inflammation
  • Dense bodies contain adenine nucleotides (ADP and ATP) and serotonin. These induce platelet aggregation, vasoconstriction, cytokine production, and modulation of inflammation.
  • Lysosomes contain glycohydrolases and proteases, that can assist in pathogen clearance, breakdown of extracellular matrix, and clearance of platelet thrombi and heparin degradation.

Role of Platelets in Vasoconstriction

• Exposed collagen from damaged surfaces encourages platelets to adhere, activate and aggregate, forming a platelet plug that seals off the injured area following vasoconstriction

Multiple Choice Questions (MCQs)

• Hemostasis: The process by which bleeding stops from damaged blood vessels
• Steps of Hemostasis: Vascular spasm, platelet plug formation, and blood clotting
• Vascular Spasm Cause: Due to damage in smooth muscle, release of substances by activated platelets, and reflex initiated by pain receptors

Additional Questions

• Substances released by activated platelets: Serotonin, ADP
• Substance helping activate other platelets: ADP

Matching the Following

• Vascular spasm: Causes contraction in the walls of blood vessels
• Platelet adhesion liberate: Sticking to the damaged part
• Platelet release action: Extend projection and substances
• Platelet accumulation: Gathering of all the platelets

Short Answer Questions

• Primary hemostasis factors: Vascular spasm, platelet adhesion, platelet activation, and platelet aggregation.
• Diseases affecting primary hemostasis: Inherited (Von Willebrand Disease, Bernard-Soulier Syndrome, Glanzmann Thrombasthenia) or acquired (drug-induced, immune thrombocytopenic purpura, chronic kidney disease, and cardiopulmonary bypass)
• Signal marking primary hemostasis termination: The formation of a platelet plug

Laboratory Test- Bleeding Time

• Bleeding time assessment of platelets' function involves measuring the time it takes for bleeding to stop.
• Normal range: 1-9 minutes (normal), 9-15 minutes (platelet dysfunction), >15 minutes (critical)
• Procedure: making a small cut, then timing how long it takes for the bleeding to stop using a standardized method and stopwatch

Secondary Hemostasis

• Coagulation, referring to blood clotting, is a sophisticated process.
• One event triggers the next, like a waterfall.
• Fibrin is an insoluble protein produced from fibrinogen, which traps platelets and other blood cells to form a robust clot.

Coagulation

• Injury to a blood vessel initiates hemostasis
• Blood clotting involves four steps:
• First, vascular spasm constricts blood flow
• Next, a platelet plug temporarily seals small openings in the vessel.
• Coagulation enables vessel wall repair once blood leakage stops
• Fibrin synthesis in blood clots involves the intrinsic or extrinsic pathways, converging to a common pathway

Clotting Factors

• Clotting factors (coagulation factors) are chemicals that activate more coagulation factors in a cascade.
• Clotting factors are dependent on vitamin K and calcium and are produced by the liver and platelets

The Liver

• The liver requires vitamin K to produce many clotting factors
• Vitamin K is also synthesized by bacteria in the large intestine
• Calcium (Factor IV) is derived from the diet and bone breakdown

Common Pathway

• Both intrinsic and extrinsic pathways lead to the common pathway
• Factor X activation by either pathway triggers thrombin production
• Thrombin converts fibrinogen to fibrin
• Factor XIII stabilizes the fibrin clot

Fibrinolysis

• The stabilized clot is acted upon by contractile proteins in the platelets.
• These proteins pull on the fibrin threads bringing the edges of the clot tightly together.
• This process also wrings out serum from the clot, which is blood plasma without its clotting factors

Fibrinolysis Summary

• Fibrinolysis is the sequential degradation of the clot to restore normal blood flow.
• Inactive plasminogen is transformed into active plasmin.
• Plasmin gradually breaks down fibrin in the clot.
• Bradykinin, a vasodilator, is released which reverses the effects of serotonin and prostaglandins produced by platelets, easing smooth muscle relaxation and circulation restoration.

Plasma Anticoagulants

• Plasma anticoagulants include proteins and substances that impede coagulation
• The protein C system inhibits intrinsic pathway factors
• TFPI inhibits extrinsic pathway factor VII conversion
• Antithrombin opposes factor Xa converting to thrombin
• Heparin is a short-acting anticoagulant released by basophils and found lining blood vessels

Labs

• Trisodium citrate (0.109 M solution) is the most common anticoagulant for coagulation samples.
• 1 volume anticoagulant to 9 volumes of blood for routine coagulation testing.

Homework

• Other anticoagulants like oxalate, heparin, and EDTA are unsuitable for coagulation samples because they interfere with factors or mechanisms involved in the process.

Test your knowledge on the coagulation process with this quiz focused on platelet plugs, bleeding time, and the coagulation pathways. Explore the first steps of blood clotting, key factors involved, and the significance of coagulation vitamins. Perfect for students in hematology or related fields.