Week 5-lec 5 Flashcards
What are the functions of normal blood hemostasis?
- Ensures fluid state of blood in vasculature
- Prevents blood loss at site of injury»forms haemostatic plug
- Clot removal (fibrinolysis)
»when healing is complete
Name 4 steps in hemostasis
- Vasoconstriction
- Platelets:
-Adhesion
-Activation
-Aggregation - Coagulation factor activation
- Fibrinolysis
Name 3 pathways of the coagulation cascade
- Intrinsic pathway
- Extrinsic pathway
- Common pathway
Discuss the activation of coagulation factors in the intrinsic pathway
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.
Discuss the activation of factors in the extrinsic pathway
Blood is exposed to tissue factor (F3)»>this activates F7 in the blood»>Active F7 activates F10
Discuss the activation of factors in the common pathway
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)
Differentiate between the 2 classes of coagulation factors
- Serine Proteases: Enzymes that cleave specific peptide bonds to activate other clotting factors (e.g., thrombin, Factor Xa).
- 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)
Name the 4 screening tests used in the diagnoses of coagulation disoders
- Thrombin time: Screens for defeciency or abnormalities on thrombin or on inhibition of thrombin by heparin
- Prothrombin time: Screens for deficiency or abnormality in the ff factors: F1, F2, F5,F7,F10
- Activated Partial thromboplastin time (APTT): Screens for deficiency or abnormality in all those factors
- Fibrinogen quantification: Screens for fibrinogen deficiency
What disoders are related to F1; Fibrinogen?
- INHERITED DISODERS:
- afibrinogenemia
- hypofibrinogenemia
- hyperfibrinogenemia - DISODERS FOLLOWING DEFICIENCY OF THE FACTOR:
-Thromboembolism or bleeding
What disoder is related to F2; Prothrombin?
INHERITED DISODER:
Bleeding- following Prothrombin G20210A mutation
What disoder result from the deficiency of F3; tissue factor?
bleeding
What disorder follows deficiency of F7?
Bleeding
What disoder result from the deficiency of F5?
- INHERITED DISODER:
prothrombotic: risk of VTED (venous thromboembolism (VTE): Following Factor V Leiden mutation - DISODER FROM FACTOR DEFICIENCY:
Owren’s disease: bleeding disorder
Name a disoder following F9 deficiency
Hemophilia B or Christmas Disease-X linked recessive
Name a genetic or acquired disoder following F8 deficiency
Hemophilia A- X linked recessive
Name a disoder following F10 deficieny
Bleeding diatheses- easy bleeds
Bleeding disoder following F11
Hemophilia C- autosomal recessive
Bleeding disoder following F12
Not hemorrhage but increased thrombosis
List the vitamin K dependent coagulation factors
- Protrombin (Factor II)
- Factor VII
- Factor IX
- Factor X
- Protein C & S
- F 2,7,9,10
List all the congenital bleeding disoders
- Haemophilia
◦A
◦B
◦C - Von Willebrand
disease (autosomal dorminant)
*Other factor
deficiencies
List all the acquired bleeding disoders
- DIC
- Liver dysfunction
- Drugs
- Acquired inhibitors
Classify hemophilia according to the level of factor in the blood
- <1%: severe
- 1-5%: moderate
- 5-30%: mild
Can female carriers be symptomatic to hemophilia?
Yes
- Occasionally female carriers can be symptomatic
-Extreme lyonization / Turners syndrome (XO)
- Deep seated bleeds
*Joints
*Brain / Muscle / Retroperitoneal
How to treat coagulation factor defect?
- 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.
Common coagulation factor inhibitors
IgG- mostly inhibits and neutralise factor 8
Clinical suspicions of auto-antibody neutralization of replaced coagulation factors from replacement therapy on patients with inherited or congenital hemophilia
- New bleeding symptoms
- Known mild haemophilia with more extreme bleeding
- Failure of factor replacement therapy to arrest bleeding in a
known haemophiliac
Neutralizing anti-FVIII / FIX antibodies or “inhibitors” against exogenous
coagulation factors
- 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
