Theme 7 Haematology: Intro to Heritable bleeding disorders Flashcards
Explain haemostasis when the vessel wall is breached
- haemostasis starts with platelet activation when the vessel wall is breached
- these activated platelets bind to collagen in the endothelium of a BV
- platelets bind to a wall of vessel and each other to form a plug –> platelet aggregation
- this is an active process
- platelet plug is stabilised by the formation of fibrin
- sticking of platelets to endothelium is supported by von willebrand factor
What does thrombin do?
converts fibrinogen to fibrin
Explain the extrinsic pathway in the coagulation cascade
- tissue factor binds to factor VII to become factor VIIa
- factor VIIa activates factor X to form factor Xa
- factor X and factor V convert thrombin to fibrin
Explain the intrinsic pathway in the coagulation cascade?
- occurs when blood is in contact with a foreign surface
1. Factor XII becomes activated to factor XIIa
2. This activates factor XI and IX
3. Factor IX and X activates factor X
Name 4 anti-coagulant factors
- protein C
- protein S
- anti-thrombin III
- fibrinolytic system
Name 2 pro coagulants
platelet
clotting factors
Which investigations should be carried out in a patient with a possible bleeding disorder?
- FBC and blood film
- coagulation screen and class fibrinogen
- von willebrand profile
- coagulation factor assays
- platelet function tests
What are the causes of bleeding in a patient with a norma coagulation screen?
- thrombocytopenia
- disorder of platelet function
- low vWD
- factor XIII deficiency
- vascular disorder
- mild coagulation factor deficiency
What are the 4 platelet/vessel wall defects that all give rise to a prolonged bleeding time?
- Thrombocytopenia (reduced number of platelets)
- Abnormal platelet function e.g drugs/heritable
- Abnormal vessel wall e.g ehlers danlos syndrome
- Abnormal interaction between platelets and vessel wall e.g von willebrand disease is commenest
What are the signs of vascular/ platelet defects?
- petechiae and superficial bruises
- spontaneous bleeding
- prolonged bleeding
What are the signs of coagulation defects?
- deep spreading haematoma
- haemarthrosis
- retroperitoneal bleeding
What is petechiae?
- pin point round spots that appear on skin as a result of bleeding
- do not blanch with pressure
- not palpable
What is the most common heritable bleeding disorder?
von willebrand disease
What are the 3 types of VW disease?
Type 1: most common - reduced production of VW factor but it functions normally
Type 2: enough VW factor is produced but its structurally abnormal
Type 3: very rare and severe where there is no VW factor
Why will patients with VW disease often have a low FVIII?
VW is a carrier protein for factor VIII
What type of inheritence is VW disease?
type 1 and 2 is autosomal dominant
type 3 is recessive
so mostly autosomal dominant
Which blood group has lower levels of vWF?
0
How do we treat VW disease?
- antifibrinolytics: tranexamic acid
- DDAVP
- factor concentrates containing vWD (plasma derived)
What is another name for:
- Factor I
- Factor II
- Fibrinogen
2. Prothrombin
How are the haemophillias inherited?
X-linked recessive disorders
Haemophilia A causes a deficiency in which factor?
factor VIII
haemophilia B causes a deficiency in which factor?
factor IX
What are the 3 degrees of severity of haemophilia?
- Mild haemophillia
- factor VIII or IX level = 6%-50%
- will only bleed after trauma - Moderate haemophilia
- factor VIII or IX level = 1%-5% - Severe haemophilia
- factor VIII or IX level = <1%
- can result in intracranial bleeding
What are the different types of bleeding?
- spontaenous / post-traumatic
- joint bleeding (haemarthrosis)
- muscle haemorrhage
- soft tissue
What is arthropathy?
any disease of the joints
How do we treat haemophilia?
- replacement of missing clotting protein
- DDAVP
- factor concentrates for severe haemophilia
- antifibrinolytic agents
- HepB and HepA vaccination
What are the complications of treatment of haemophilia?
- transfusion transmitted infection
- inhibitor development
What is inhibitor development?
- antibodies developed against factor VIII (and IX but less common)
- more common in haemophilia A than B
- results in poor recovery and/or shortened half life of factor replacement therapy
What is emicizumab (Hemlibra)?
- monoclonal antibody therapy for haemophilia A
- with or without inhibitors
- it replaces the action of the missing FVIII so blood can clot
