Hemostasis (Ch. 22)-- Definition First

Question 1

Actin & Myosin contract → Fibrin strands pulled toward platelet plug → Clot retraction → Plasma (liquid) squeezed out of clot → Clot shrinks

Answer 1

Fourth Step of Hemostasis

Question 2

• Autosomal dominant coagulation disorder
  
  • Deficiency or defect in vWf
• Mild-moderate bleeding

Treatment– DDAVP (Desmopressin Acetate) an analog of ADH/Vasopressin

Answer 2

von Willebrand Disease

Question 3

• Platelet count out of range
• Abnormal platelet function
• Coagulation factor dysfunction
• Loss of blood vessel integrity

Answer 3

Causes of Blood Disorders

Question 4

Activation, adhesion & aggregation of platelets → Platelet plug

Damaged vessel → Activation of platelets

Endothelial cells → vWf → Binds platelet receptors (GPIIb/IIa) to vessel wall → Adhesion

Platelets release mediators (ADP & TXA₂) → Aggregation

Answer 4

Second Step of Hemostasis

Question 5

• X-linked recessive coagulation disorder
  
  • Factor VIII deficiency
    
    • Works w/ vWf to promote adhesion
• S/S
  
  • Mild
    
    • Bleeding w/ trauma/injury
  • Severe
    
    • Spontaneous, uncontrolled bleeding

Treatment– Factor VIII replacement therapy

Answer 5

Hemophilia A

Question 6

• 3 Stages
  
  • Vascular constriction
    
    • Vessel spasm → ⇣ Blood flow
  • Platelet Plug (unstable)
    
    • Platelets play a major role
  • Blood coagulation (stable)
    
    • Clotting factors (CF) play a major role
• End result
  
  • Fibrin (CF Ia)
    
    • Rope-like substance wraps around platelet plugs
    • Structural basis of clot
  • Blood becomes gel-like
    
    • Traps RBCs in clot
  • Clot & fibrous tissue grow together
    
    • Seal hole in vessel wall

Answer 6

Mechanisms of Hemostasis

Question 7

• Factor I to XII
  
  • Synthesized in liver (mostly)
  • Factor X
    
    • Beginning of final common pathway
  • Factor VIII
    
    • Not present in hemophilia
  • Factor I (Fibrinogen)
  • Factor Ia (Fibrin)
  • Factor II (Prothrombin)
  • Factor IIa (Thrombin)
  • Factor IV (Calcium)
• Vitamin K
  
  • Required to make CF II, VII, IX, & X

Answer 7

Plasma Clotting Factors

Question 8

Thrombocytopenia (platelets < 150,000/uL) → Bleeding disorder

d/t– Drug-induced, Malignancies, Immune response, Pooling of platelets in the spleen (sequestration)

Manifestation– Petechiae (platelet count < 20,000/uL in small vessels)

Answer 8

Low Platelet Count

Question 9

Requires Ca²⁺

• Intrinsic pathway
  
  • Inside vessel wall
    
    • Ex: Atherosclerosis
  • Slow
    
    • 1-6 min.
  • Begins in circulation
  • Factor XII activated
• Extrinsic Pathway
  
  • Outside wall of the vessel
    
    • Ex: Gunshot wound
  • Faster
    
    • 15 sec.
  • Factor III activated
• Final Common Pathway
  
  • Both pathways converge @ Factor X
    
    • Factor II → IIa (Prothrombin → Thrombin)
    • Factor I to Ia (Fibrinogen → Fibrin)

Answer 9

Clotting Cascade

Question 10

Impaired platelet function → Bleeding disorder

d/t– ASA/NSAID use (ASA irreversibly ⇣ TXA₂ activity), Adhesion disorder (von Willebrand disease)

Answer 10

Thrombocytopathia

Question 11

Clotting Cascade:

Factor XII activated → Intrinsic pathway (slow, begins in circulation)

Factor III activated → Extrinsic pathway (fast, exposed tissue)

Factor X activated → Final common pathway → Fibrinogen (H₂O soluble) → Fibrin (H₂O insoluble)

Answer 11

Third Step of Hemostasis

Question 12

Endothelial cells → tPA → Plasminogen → Plasmin (active) → Digestion of fibrin strands → Clot dissolution (Fibrinolysis)

Answer 12

Fifth Step of Hemostasis

Question 13

Clotting/Stoppage of Blood Flow

Red blood cells trapped in fibrin meshwork (semisolid clot)

Clot=Thrombus

• Normal
  
  • Blood vessel seals to stop bleeding
• Abnormal
  
  • Thrombosis
    
    • Inappropriate formation of blood clots
  • Hemorrhage
    
    • Failure to form a blood clot in the presence of bleeding

Answer 13

Hemostasis

Question 14

• Bleeding
• Petechiae
• Oozing from puncture sites
• Severe hemorrhage
• Hypoxia & organ damage
  
  • Microemboli obstruct blood vessels
    
    • Renal, circulatory, or respiratory failure
      
      • Convulsions
      • Coma

Treatment– Manage primary disease, Replace clotting components (Factor VIII, FFP (fresh-frozen plasma), platelets, cryoprecipitate), Heparin

Answer 14

Clinical Manifestations of Disseminated Intravascular Coagulation (DIC)

Question 15

Major role in platelet adhesion & blood clotting

• von Willebrand Factor (vWf) Synthesis
  
  • Required for blood clotting
  • Cell wall integrity disrupted → vWf → Aggregation
• Promote blood flow
  
  • Block platelet adhesion
  • Inhibit coagulation
  • Clot lysis

Answer 15

Endothelial Cells

Question 16

• PT/INR
  
  • Prothrombin time
    
    • Time (sec.) it takes for blood to clot
    • Extrinsic pathway
• PTT
  
  • Partial prothrombin time
    
    • Time (sec.) it takes for blood to clot
    • Intrinsic pathway
• ⇡ PT/PTT/INR
  
  • Clotting too slow
  • ⇡ Risk of hemorrhage
• ⇣ PT/PTT/INR
  
  • Clotting too fast
  • ⇡ Risk of clotting

Answer 16

Blood Coagulation Clinical Assessment (“Coags”)

Question 17

• Anuclear fragment of megakaryocyte
• Originate from myeloid stem cells
  
  • Life span: 8-12 days
  • Normal levels: 150,000-400,000 cells/uL
• Thrombopoietin
  
  • Hormone that stimulates thrombocyte proliferation
    
    • Released from liver & kidneys
• Function
  
  • Aggregate → Blood coagulation & Vessel repair
• Components
  
  • Glycoprotein Ilb/Ila (GPIIb/IIa)
  • ADP
  • Serotonin
  • Thromboxane (TXA₂)
  • Actin/Myosin II
  • Alpha & Delta Granules
    
    • Secrete mediators

Answer 17

Platelets (Thrombocytes)

Question 18

INJURY → Vasoconstriction/Vessel Spasm → ⇣ Blood flow from rupture

Nerve reflexes & Humoral factors → Short vessel spasm

Platelets → TXA₂ → ⇡ Aggregation & Vasoconstriction

Answer 18

First Step of Hemostasis

Question 19

Widespread coagulation and bleeding due to underlying disorder

d/t– Obstetric complication, Malignant neoplasms, Systemic infections (Sepsis), Severe trauma, Surgery, Burns (extrinsic pathway), Endothelial or tissue injury (intrinsic pathway)…

• MASSIVE activation of clotting pathway
  
  • Excessive thrombin generation
    
    • Fibrinogen converted to fibrin via thrombin
    • Fibrin deposited in capillaries
    • Systemic microvascular clots
• Vicious cycle (steps 3-5 repeat)
  
  • Clotting, dissolution (bleeding), clotting, dissolution (bleeding)…
• Uncontrolled, excessive bleeding
  
  • All clotting factors have been used up

Answer 19

Disseminated Intravascular Coagulation (DIC)

Question 20

• Endogenous anticoagulants
  
  • Released simultaneously w/ blood clot formation
    
    • Inactivate clotting factors
      
      • Antithrombin III
      • Proteins C & S
    • Plasminogen (proenzyme) → Plasmin (active)
      
      • Converted by tissue plasminogen activator (tPA)– AKA “clot buster”
      • Plasmin digests fibrin strands & degrades clot

Answer 20

Fibrinolysis (Clot Dissolution)