Blood: Hemostasis, Clotting, and Transfusion – Anatomy & Physiology I Study Notes

Blood: Hemostasis, Clotting, and Transfusion

Overview

This section covers the physiology of blood, focusing on hemostasis, coagulation, clot retraction and fibrinolysis, disorders of hemostasis, and the principles of blood transfusion including blood groups and transfusion reactions. These topics are essential for understanding the cardiovascular system and its role in maintaining homeostasis.

Hemostasis

Coagulation

Hemostasis is the process that stops bleeding after vascular injury. Coagulation is a critical phase where blood is transformed from liquid to gel, reinforcing the platelet plug with fibrin threads to seal larger vessel breaks.

• Clotting factors (procoagulants): Mostly plasma proteins, numbered I to XIII in order of discovery. Vitamin K is required to synthesize four of these factors.

• Phases of Coagulation:

  1. Phase 1: Formation of prothrombin activator via two pathways:

     • Intrinsic pathway: Clotting of blood outside the body (e.g., in a test tube) or in slightly damaged vessels. Triggered by negatively charged surfaces such as collagen.

     • Extrinsic pathway: Clotting in response to tissue damage, initiated by release of tissue factor (TF, also called factor III). This pathway is faster as it bypasses several steps of the intrinsic pathway.

     • Both pathways converge at activation of Factor X, which complexes with Ca2+, PF3 (platelet factor 3), and factor V to form prothrombin activator.

  2. Phase 2: Prothrombin activator catalyzes the transformation of prothrombin to active enzyme thrombin.

  3. Phase 3: Thrombin converts soluble fibrinogen to fibrin. Fibrin strands form a structural basis of the clot, causing plasma to become a gel-like trap. Thrombin (with Ca2+) activates factor XIII (fibrin stabilizing factor), which cross-links fibrin and strengthens the clot.

Equation:

• $\text{Prothrombin} \xrightarrow{\text{Prothrombin Activator}} \text{Thrombin}$

• $\text{Fibrinogen} \xrightarrow{\text{Thrombin}} \text{Fibrin}$

Blood Clotting Factors (Procoagulants)

Blood clotting involves a cascade of plasma proteins, each with a specific role. The following table summarizes the main clotting factors:

Factor Number	Factor Name	Source	Main Function
I	Fibrinogen	Plasma protein	Forms fibrin threads of clot
II	Prothrombin	Plasma protein	Converted to thrombin
III	Tissue factor (TF)	Plasma membrane glycoprotein	Activates extrinsic pathway
IV	Calcium ions (Ca2+)	Plasma	All pathways
V	Proaccelerin	Plasma protein	Common pathway
VIII	Antihemophilic factor	Plasma protein	Intrinsic pathway
XIII	Fibrin stabilizing factor	Plasma protein	Cross-links fibrin, stabilizes clot
Additional info:	Other factors (VII, IX, X, XI, XII)	Plasma proteins	Various roles in intrinsic/extrinsic pathways

Clot Retraction & Fibrinolysis

After a clot forms, it must be stabilized and eventually removed as healing occurs.

• Clot Retraction: Actin and myosin in platelets contract within 30–60 minutes, pulling on fibrin strands and squeezing serum from the clot. This draws ruptured blood vessel edges together.

• Platelet-derived growth factor (PDGF): Released by platelets, stimulates division of smooth muscle cells and fibroblasts to rebuild vessel wall.

• Vascular endothelial growth factor (VEGF): Stimulates endothelial cells to multiply and restore lining.

Fibrinolysis

Fibrinolysis is the process of clot removal when it is no longer needed.

• Key enzyme: Plasmin (precursor: plasminogen, a plasma protein incorporated into the clot).

• Plasminogen is activated by tPA (tissue plasminogen activator) released by endothelial cells.

• Begins within 2 days and continues until the clot is dissolved.

Equation:

• $\text{Plasminogen} \xrightarrow{\text{tPA}} \text{Plasmin}$

Factors Limiting Clot Growth or Formation

Mechanisms Limiting Clot Size

Normal clot growth is limited by two main mechanisms:

• Swift removal and dilution of clotting factors by flowing blood.

• Inhibition of activated clotting factors by plasma proteins.

Key inhibitors include:

• Antithrombin III: Inactivates any escaping thrombin.

• Protein C: Inactivates many intrinsic pathway procoagulants.

• Heparin: Released by basophils and mast cells, enhances activity of antithrombin III.

• Endothelial lining: Smooth lining prevents undesirable clotting; also releases nitric oxide (NO) and prostacyclin.

Disorders of Hemostasis

Thromboembolic Disorders

These disorders involve undesirable clot formation within blood vessels.

• Thrombus: Clot that develops and persists in an unbroken vessel, potentially blocking circulation and causing tissue death.

• Embolus: Thrombus freely floating in the bloodstream.

• Embolism: Embolus obstructing a vessel (e.g., pulmonary or cerebral embolism).

• Risk factors: Atherosclerosis, inflammation, slow blood flow, or stasis from immobility.

• Treatment: Drugs such as tPA or streptokinase to dissolve clots via plasmin.

Bleeding Disorders

• Thrombocytopenia: Deficient number of circulating platelets, often due to bone marrow suppression or destruction. Platelet count <50,000/μl is diagnostic. Treatment is transfusion of concentrated platelets (temporary relief).

• Impaired liver function: Inability to synthesize procoagulants (clotting factors). Causes include vitamin K deficiency, hepatitis, or cirrhosis. Liver disease can also prevent bile production, which is needed to absorb vitamin K.

• Hemophilia: Hereditary bleeding disorders. Hemophilia A (factor VIII deficiency) is most common; Hemophilia B (factor IX deficiency).

Blood Transfusion

Principles of Blood Transfusion

Blood transfusion is used to replace lost blood volume or treat anemia. The cardiovascular system compensates for blood loss by reducing vessel volume and increasing RBC production, but only up to a point.

• Volume replacement: Normal saline or Ringer's solution mimics plasma electrolyte composition.

• Whole blood transfusion: Used for substantial blood loss or thrombocytopenia.

• Packed red cells (PRBC): Used for anemia; donor blood is mixed with heparin (anticoagulant).

• Blood typing: Essential to prevent transfusion reactions; donor blood groups must be determined.

Human Blood Groups

ABO Blood Groups

Blood groups are classified based on the presence or absence of antigens (agglutinogens) on the surface of RBCs.

• Antigens: A and B are the main agglutinogens.

• Antibodies (agglutinins): Blood may contain anti-A or anti-B antibodies, which act against transfused RBCs with antigens not present on recipient's RBCs.

Blood Type	Antigens on RBCs	Antibodies in Plasma	Can Receive From
A	A	Anti-B	A, O
B	B	Anti-A	B, O
AB	A and B	None	A, B, AB, O
O	None	Anti-A and Anti-B	O

Additional info: Type O is the universal donor (no antigens), type AB is the universal recipient (no antibodies).

Rh Blood Groups

Rh blood groups are determined by the presence of Rh antigens (D, C, E are most common). Rh+ indicates presence of D antigen; 85% of North Americans are Rh+.

• Anti-Rh antibodies are not spontaneously formed in Rh- individuals but can form after exposure to Rh+ blood.

• Second exposure to Rh+ blood results in typical transfusion reaction.

• Rh- mothers carrying Rh+ babies are treated with RhoGAM (anti-Rh serum) to prevent erythroblastosis fetalis (hemolytic disease of the newborn).

Transfusion Reactions

Mechanism and Consequences

Transfusion reactions occur if mismatched blood is infused. The problem arises from recipient's antibodies (agglutinins) acting against donor RBC antigens.

• Agglutination and clogging of small vessels.

• RBCs rupture, releasing hemoglobin into bloodstream.

• Blocked flow to tissues and reduced oxygen-carrying ability.

• Hemoglobin precipitates and clogs kidney tubules, possibly leading to kidney failure.

• Symptoms: fever, chills, nausea, vomiting, general toxicity.

• Treatment: administer alkaline fluids to dilute and dissolve hemoglobin; use diuretics.

• Autologous transfusion: patient donates own blood prior to surgery.

Blood Typing

Principles of Blood Typing

Blood typing is performed by mixing donor blood with antibodies against common agglutinogens. If agglutinogen is present, clumping of RBCs will occur.

• Blood is typed for ABO and Rh factor.

• Cross matching: Typing between specific donor and recipient. Mix recipient's serum with donor RBCs and vice versa.

Review Questions

• Fibrinolysis is increased by: Activation of plasminogen, release of tPA, and heparin.

• Transfusion reaction concerns: Clogging of small vessels, lysis of donated RBCs, blockage of kidney tubules; donor antibodies attacking recipient RBCs is not a major concern.