Chapter 12 - Hemostasis

Stage 1 of Hemostasis

Vessel Spasm: MOI that activates local and humoral mechanisms that cause transient (>1 min) vessel spasm. During this time, vascular smooth muscle contracts to reduce blood flow to the damaged area. This vasoconstriction is supported by local neural reflexes and humoral factors (thromboxane A2 (aka: TXA2)) released from platelets.

Stage 2 of Hemostasis

Formation of the platelet plug: Begins with von Willebrand factor (vWF) released from the endothelium allows platelets to adhere to exposed collagen in the damaged vessel wall. The adhered platelets then become activated and release ADP and TXA2 which promote further platelet aggregation and lead to plug formation. Aspirin inhibits platelet aggregation by blocking TXA2 production.

Stage 3 of Hemostasis

Blood coagulation or development of an insoluble fibrin clot: Blood coagulation occurs when insoluble fibrin threads form and stabilize the clot by holding the platelet plug together. Anticoagulants such as heparin, released from mast cells, help prevent excessive fibrin formation and limit clotting, while warfarin is an anticoagulant drug that reduces prothrombin activity.

Stage 4 of Hemostasis:

Clot retraction: Within 20–60 minutes, actin and myosin within platelets contract, squeezing serum from the clot and pulling the edges of the damaged vessel together. Failure of clot retraction indicates a low platelet count.

Stage 5 of Hemostasis:

Clot Dissolution: Fibrinolysis allows blood flow to be reestablished and tissue repair to occur as the clot is broken down. Plasminogen activators such as tPA and uPA convert plasminogen into plasmin, which digests the fibrin strands of the clot.

Thrombocytopenia

a condition in which the platelet count is abnormally low. It can result from decreased platelet production due to bone marrow suppression, increased platelet destruction by the immune system (such as antiplatelet antibodies), or excessive platelet use during conditions like disseminated intravascular coagulation (DIC) or massive clotting. As a result, patients are at risk of excessive or prolonged bleeding.

Hypercoagulability states

Conditions or factors that predispose to thrombosis (increase the likelihood of a blood clot) and blood vessel occlusion (block a blood cell). Two general forms:

1. Increase in platelet function: (or an increase in platelet number) can raise the risk of clot formation. Blood flow disturbances, such as turbulence or stasis, also promote thrombosis, often due to endothelial damage and increased platelet aggregation. Blood flow disturbances are commonly caused by atherosclerosis.

2. Increase in clotting activity: may occur when procoagulation factors are elevated or anticoagulation factors are reduced, and these changes can be either inherited or acquired. Acquired causes include prolonged bed rest, use of oral contraceptives, myocardial infarction (MI), as well as smoking and obesity.

Thrombocytopathia

When platelets present in normal numbers but function is impaired. his can impair platelet aggregation and clot formation, leading to an increased risk of bleeding, even though the platelet count is normal. It can be inherited or acquired:

• Inherited: von Willebrand disease.

• Acquired: NSAIDs and aspirin inhibit TxA₂ production → decreased aggregation.

Platlet Production

Aka thrombopoiesis. Thrombopoietin is a hormone that stimulates platelet production in the bone marrow. It is produced mainly by the liver and kidneys, as well as by smooth muscle and bone marrow cells. Platelets contain two main types of granules. Alpha (α) granules store fibrin, coagulation factors, plasminogen, platelet-activating factor (PAF), and platelet-derived growth factors (PDGFs). Dense (δ or beta) granules contain ADP, ATP, calcium ions (Ca²⁺), serotonin, and histamine, which are released to help with clot formation and vascular responses.

Mechanism of action of aspirin

Irreversibly inhibits the enzyme cyclooxygenase (COX-1 and COX-2) in platelets. This prevents the formation of thromboxane A₂ (TXA₂), a molecule that normally promotes platelet aggregation and vasoconstriction. As a result, aspirin reduces platelet aggregation and helps prevent blood clots, lowering the risk of heart attack and stroke.

Role of the endothelium

The endothelial surface of blood vessels normally prevents platelets and plasma coagulation factors from interacting with the thrombogenic subendothelial extracellular matrix (ECM). Healthy, intact endothelial cells produce several substances that inhibit platelet adhesion and aggregation. These include prostaglandin I₂ (PGI₂), which prevents platelet activation, and nitric oxide (NO), which stops active platelets from sticking to uninjured areas of the vessel wall. Endothelial cells also produce ADPase, which degrades ADP to reduce platelet activation, and tissue plasminogen activator (tPA), which helps clear fibrin debris and maintain blood flow.

Hemophilia A

An inherited coagulation disorder caused by a deficiency of clotting factor VIII. It is an X-linked recessive disorder, meaning it primarily affects males, while females are usually carriers. The severity of Hemophilia A is classified as mild, moderate, or severe, depending on the level of factor VIII and the tendency to bleed. This condition leads to prolonged bleeding because the blood cannot clot properly.