Week 5-lec 5

Question 1

What are the functions of normal blood hemostasis?

Answer 1

• Ensures fluid state of blood in vasculature
• Prevents blood loss at site of injury»forms haemostatic plug
• Clot removal (fibrinolysis)
  »when healing is complete

Question 2

Name 4 steps in hemostasis

Answer 2

1. Vasoconstriction
2. Platelets:
   -Adhesion
   -Activation
   -Aggregation
3. Coagulation factor activation
4. Fibrinolysis

Question 3

Name 3 pathways of the coagulation cascade

Answer 3

1. Intrinsic pathway
2. Extrinsic pathway
3. Common pathway

Question 4

Discuss the activation of coagulation factors in the intrinsic pathway

Answer 4

Prekallikrein (PK) and High-Molecular-Weight Kininogen (HK) (from the liver), activate factor 12»>activated F12 activate F11»>Activated F11 activate F9»>Activated F9 and F8a form tenase»>which will activate F10

F11 and F8 are activated by thrombin. Basically, F11 is activated through 2 ways.

Question 5

Discuss the activation of factors in the extrinsic pathway

Answer 5

Blood is exposed to tissue factor (F3)»>this activates F7 in the blood»>Active F7 activates F10

Question 6

Discuss the activation of factors in the common pathway

Answer 6

F10 together with calcium, phospholipids, F5 form prothrombinase»> Prothrombinase catalyses the conversion of prothrombin (inactive F2) to thrombin (active F2)»>Thrombin activates fibrinogen to fibrin»> Activated F13 stabilises the clot (activated by thrombin)

Question 7

Differentiate between the 2 classes of coagulation factors

Answer 7

1. Serine Proteases: Enzymes that cleave specific peptide bonds to activate other clotting factors (e.g., thrombin, Factor Xa).
2. Co-factors: Proteins that enhance the activity of serine proteases by forming complexes with them, but do not perform proteolytic cleavage themselves (e.g., Factor V, Factor VIII)

Question 8

Name the 4 screening tests used in the diagnoses of coagulation disoders

Answer 8

1. Thrombin time: Screens for defeciency or abnormalities on thrombin or on inhibition of thrombin by heparin
2. Prothrombin time: Screens for deficiency or abnormality in the ff factors: F1, F2, F5,F7,F10
3. Activated Partial thromboplastin time (APTT): Screens for deficiency or abnormality in all those factors
4. Fibrinogen quantification: Screens for fibrinogen deficiency

Question 9

What disoders are related to F1; Fibrinogen?

Answer 9

1. INHERITED DISODERS:
   - afibrinogenemia
   - hypofibrinogenemia
   - hyperfibrinogenemia
2. DISODERS FOLLOWING DEFICIENCY OF THE FACTOR:
   -Thromboembolism or bleeding

Question 9

What disoder is related to F2; Prothrombin?

Answer 9

INHERITED DISODER:
Bleeding- following Prothrombin G20210A mutation

Question 9

What disoder result from the deficiency of F3; tissue factor?

Answer 9

bleeding

Question 10

What disorder follows deficiency of F7?

Answer 10

Bleeding

Question 11

What disoder result from the deficiency of F5?

Answer 11

• INHERITED DISODER:
  prothrombotic: risk of VTED (venous thromboembolism (VTE): Following Factor V Leiden mutation
• DISODER FROM FACTOR DEFICIENCY:
  Owren’s disease: bleeding disorder

Question 12

Name a disoder following F9 deficiency

Answer 12

Hemophilia B or Christmas Disease-X linked recessive

Question 12

Name a genetic or acquired disoder following F8 deficiency

Answer 12

Hemophilia A- X linked recessive

Question 13

Name a disoder following F10 deficieny

Answer 13

Bleeding diatheses- easy bleeds

Question 14

Bleeding disoder following F11

Answer 14

Hemophilia C- autosomal recessive

Question 15

Bleeding disoder following F12

Answer 15

Not hemorrhage but increased thrombosis

Question 15

List the vitamin K dependent coagulation factors

Answer 15

• Protrombin (Factor II)
• Factor VII
• Factor IX
• Factor X
• Protein C & S
• F 2,7,9,10

Question 16

List all the congenital bleeding disoders

Answer 16

• Haemophilia
  ◦A
  ◦B
  ◦C
• Von Willebrand
  disease (autosomal dorminant)

*Other factor
deficiencies

Question 17

List all the acquired bleeding disoders

Answer 17

• DIC
• Liver dysfunction
• Drugs
• Acquired inhibitors

Question 17

Classify hemophilia according to the level of factor in the blood

Answer 17

• <1%: severe
• 1-5%: moderate
• 5-30%: mild

Question 18

Can female carriers be symptomatic to hemophilia?

Answer 18

Yes
- Occasionally female carriers can be symptomatic
-Extreme lyonization / Turners syndrome (XO)

• Deep seated bleeds
  *Joints
  *Brain / Muscle / Retroperitoneal

Question 18

How to treat coagulation factor defect?

Answer 18

• Factor replacement:
  ◦Viral inactivation of donated factor concentrates
  -On demand or prophylactic
  ◦ Recombinant production
• DDAVP (Desmopressin): release VWF from stores
• Supportive measures
  ◦Analgesia / Physio / Genetic counseling / Joint replacements
• Gene therapy.

Question 18

Common coagulation factor inhibitors

Answer 18

IgG- mostly inhibits and neutralise factor 8

Question 19

Clinical suspicions of auto-antibody neutralization of replaced coagulation factors from replacement therapy on patients with inherited or congenital hemophilia

Answer 19

• New bleeding symptoms
• Known mild haemophilia with more extreme bleeding
• Failure of factor replacement therapy to arrest bleeding in a
  known haemophiliac

Question 20

Neutralizing anti-FVIII / FIX antibodies or “inhibitors” against exogenous
coagulation factors

Answer 20

• Approximately 25-30% of patients with severe hemophilia A develop inhibitors against Factor VIII. These inhibitors neutralize the activity of infused Factor VIII, making standard replacement therapy ineffective
• About 2-3% of patients with hemophilia B develop inhibitors against Factor IX.

TREATMENT:
◦ Bypassing agents
◦ Immune tolerance induction protocols