Immunology lecture 3

Hemostasis

• Defined as the process of stopping bleeding, involving platelet plug formation and coagulation.
• Disorders arise from an imbalance in hemostatic forces leading to two major outcomes:
  • Excessive Bleeding: Associated with vessel wall defects, platelet disorders, and coagulation disorders.
  • Excessive Clotting: Results from hypercoagulation states, causing arterial and venous thrombosis.

Platelet Disorders

Von Willebrand Disease (vWD)

• Caused by deficient levels of von Willebrand factor (vWF), crucial for platelet adhesion and factor VIII binding.
• Types of vWD include:
  • Type 1: Most common, least severe; characterized by decreased levels of vWF and factor VIII.
  • Type 2: Intermediate severity with several subtypes.
  • Type 3: Rare, severe form; characterized by nearly absent vWF and factor VIII.
• Symptoms include easy bruising, frequent nosebleeds, and heavy menstrual bleeding.
• Treatment options include Desmopressin (DDAVP) to stimulate vWF and factor VIII release or vWF replacement therapy.

Thrombocytopenia

• Defined as a condition with a low platelet count, which can result in increased bleeding risk.

Additional Blood Disorders

• Anemia: Caused by a deficiency in red blood cells or hemoglobin, leading to fatigue and weakness.
• Hemophilia: A genetic disorder characterized by difficulty in blood clotting due to insufficient clotting factors.
• Arterial Thrombosis: Formation of a blood clot in an artery, which can lead to heart attacks or strokes.
• Deep Vein Thrombosis (DVT): Occurs when a blood clot forms in a deep vein, commonly in the legs, leading to swelling and pain.

Hemostasis

• Definition: A physiological process to halt bleeding through the formation of a platelet plug and subsequent coagulation.
• Disorders: Arise from imbalances in the body's hemostatic mechanisms.
• Excessive Bleeding: Caused by three main factors:
  • Vessel wall defects
  • Platelet disorders
  • Coagulation disorders
• Excessive Clotting: Results from hypercoagulation states, leading to:
  • Arterial thrombosis
  • Venous thrombosis

Platelet Disorders

Von Willebrand Disease (vWD)

• Cause: Results from inadequate levels of von Willebrand factor (vWF), essential for platelet adhesion and stabilizing factor VIII.
• Types:
  • Type 1: Most prevalent, mild form with decreased vWF and factor VIII levels.
  • Type 2: Moderately severe with multiple subtypes.
  • Type 3: Rare and severe variant with near absence of both vWF and factor VIII.
• Symptoms: Common signs include easy bruising, frequent nosebleeds, and heavy menstrual bleeding.
• Treatment: Options include desmopressin (DDAVP) to promote the release of vWF and factor VIII, or direct vWF replacement therapy.

Thrombocytopenia

• Definition: A condition characterized by a low platelet count, leading to increased bleeding risk.

Platelet Plug Formation

Platelet Adhesion

• Platelets bind to exposed collagen in damaged blood vessels.
• Von Willebrand Factor (vWF) facilitates adhesion, linking collagen and platelet glycoprotein receptors (specifically GPIb-IX-V).
• The adhesion of platelets leads to their activation.

Platelet Activation

• Activated platelets undergo shape changes, developing pseudopodia to enhance surface area.
• They release granules containing vital substances: ADP, thromboxane A2 (TXA2), and serotonin.
• These released substances attract additional platelets and promote further activation, amplifying the response.

Thrombus Formation

• Aggregated activated platelets create a temporary "platelet plug."
• The coagulation cascade produces a fibrin mesh that stabilizes the platelet plug.
• Thrombi can be categorized as arterial (white thrombus, primarily composed of platelets) or venous (red thrombus, richer in fibrin and red blood cells).

Coagulation Cascade

• Comprises intrinsic and extrinsic pathways leading to the generation of thrombin.
• Thrombin's role is crucial as it converts fibrinogen into fibrin, essential for clot formation.
• The intrinsic pathway is triggered by damage to vascular endothelium, while the extrinsic pathway is activated by tissue factor (TF) released from damaged tissues.

Fibrinolysis

• This is the mechanism by which clots are dissolved once the blood vessel is healed.
• Plasminogen, integrated into the clot, is activated to plasmin, an enzyme that digests fibrin.
• Fibrinolysis is controlled by plasminogen activators (like tPA) and inhibitors (such as PAI-1).

Coagulation

• Refers to a series of enzymatic reactions ultimately resulting in a stable blood clot.
• Involves numerous clotting factors, labeled with Roman numerals I to XIII, most of which are produced in the liver.
• Calcium ions (Ca2+) and phospholipids play a critical role in several stages of the coagulation cascade.