Heritable bleeding disorders Flashcards
What is the process by which platelets AGGREGATE to the injury site?
- Damage to vascular wall
- Platelets adhere to point of injury
- Sticks to vWf (activates platelets) and then collagen
- Platelet plugs holes
- Require fibrin formation to stabilise clot
What intracellular processes are involved in the positive activation of more platelets?
Thromboxin release - constricts blood vessels and activates platelets
Alpha granules - coagulation factors, adhesion proteins, firbonolytics factors etc
What is the platelet receptor for fibrinogen?
Glycoprotein 2B3A
What is the platelet receptor for vWf?
Glycoprotein 1B9
How does aspirin mediate its function?
COX inhibitor - enzyme which synthesis thromboxin in platelet
What are the action of 2B3A antagonists?
Prevent platelet fibrinogen adhesion
What factors are activated by thrombin?
V, VIII, XI, XIII
What comprises the extrinsic coagulation cascade?
TF, VII
What comprises the extrinsic coagulation cascade?
TF, VII, X (along with factor V)
What comprises the intrinsic tissue cascade?
XII, XI, IX, VIII
What comprises the common pathway of the coagulation cascade?
X, V and prothrombin
What is the pathway that prothrombin time is timing?
Extrinsic/common pathway
TF substitute (fibroplatin) see how long it takes for fibrin to form)
What is the activated partial thromboplastin time counting?
Intrinsic pathway
foreign regents added e.g. silica based - activated factor 12
If prothrombin time is high, where do the deficiencies i.e.?
Factors in the extrinsic and common pathway
During activated partial thromboplastin timing, what is added to the mixture and why?
Calcium and phospholipids
Platelet substitute and some factors are calcium dependent
What effects the activated partial thromboplastin time?
Abnormalities in the INTRINSIC or common pathway
What 3 investigations that comprise a coagulation screen?
- Prothrombin time
- Activated partial thromboplastin time
- Thrombin clotting Time
What is the thrombin clotting time timing?
Time from thrombin added to plasma to formation of fibrin clot
What factors are involved in anticoagulation?
Protein C/S
Anti-thrombin III
Fibrinolytic system
What does the fibrinolytic system comprise?
Activation of plasminogen to plasmin (T-PA; tissue plasmin activation factor)
Breakdown of fibrin to fibrinogen degradation products (by plasmin)
How is this fibrinolytic system taken advantage of with an MI?
Use of T-PA to break down clot!
How are bleeding disorders characterised?
- Acquired
- Congenital
- Coagulation disorgers
- Aggregation/adhesion disorders
What sort of bleeding patters would you observe for secondary bleeding/coagulation defects?
Deep muscular and joint bleeds (haemarthitris)
Deep spreading haematomas
Retroperitoneal bleeding
Prolonged, recurrentbleeding
What sort of patterns of bleeding would you observe with primary bleeding/platelet aggregation disorders? e.g. vWf
-Mucocutaneous bleeding inc heavy periods
Petechiae/superficial bleeds
- Nose bleeds
- Immediate, prolonged bleeds, non-recurrent
What are the main types of defects you observe with platelet/vessel wall defects?
Reduced platelet number
Abnormal platelet function - e.g. production of thromboxane, dysfunctional receptors
Abnormal vessel wall e.g. collagen and survey
Abnormal interaction between platelet and vessel wall e.g. vW disease
What do all platelet/vessel or coagulation defects all end up causing?
Prolonged bleeding
What are the three types of vW disease?
Type I - some proteins absent but maintains multimeric structure - mild bleeding
Type 2 - right number of proteins but abnormal multimeric structure - mild bleeding
Type 3 - no vWf at all - severe bleeding
What are the vW disease types inheritance patterns?
Type1/2 - autosomal dominant
Type 3 - autosomal recessive
What is the other function for vWf?
Carrier protein for factor VIII
Therefore, reduced VIII level
Defects of coagulative disorders may present e.g. deep bleeding/haemoarthiritis
For vWd are male or females more effected?
F=M (autosomal dominant inheritance)
What is the treatment for vW disease/
Antifibrinolytics - tranexamic acid
Factor concentrates containing vWf
Blood donation with vWf
What factor is associated with haemophilia A?
Factor 8
What factor is associated with haemophilia B?
Factor 9
What is the inheritance pattern for haemophilia A/B
Sex linked recessive
What factor is von villibrand factor associated with?
Factor 8 - transport protein
What is the inheritance patterns for factors I, II, V, VII, X, XIII
Autosomal recessive
What is the inheritance pattern for factors XII and XI?
Autosomal dominant
What are the chances of a son/daughter being a carrier/suffer for Haemophilia A/B if mother is carrier?
50% for son to be suffers, females being carrier
What are the chances of the sons being suffers and daughters being carriers if father has haemophilia A/B
All Daughters will be carriers
No sons will be suffers
What is the degree of haemophilia dependent on?
Family severity - sons will not be more/less effected - the same
What are the degrees of severity of haemophilia?
Normal 50-150%
Mild 6- 50%
Moderate 1 -5%
Severe
What are the types of bleeds you get with haemophilia? What are the types of bleeds dependent on?
- Spontaneous
- Traumatic bleeds
Severity of haemophilia - i.e. more severe, easily bleeding!
Haemoarthiritis
Muscle bleeds
Soft tissue bleeds
Life threatening e.g. cranial/airway
What are the treatment options for haemophilia A/B
Replacement of clotting factors
Antifibrinolytics e.g. tranexamic acid
