Definition of von Willebrand disease (VWD)?
most common inherited cause of abnormal bleeding. It is usually due to a reduced quantity or reduced quality of von Willebrand factor.
Risk factors for VWD
Family history
The underlying genetic causes of VWF is what?
Autosomal dominant
The causes involve a deficiency, absence or malfunctioning of von Willebrand factor (VWF).
Type 1 VWF pathophysiology
most common, autosomal dominant condition and can lead to reduced or defective production of vWF
Type 2 VWF pathophysiology
quantity of vWF is fine but quality is affected. 4 subtypes
- A: vWF can attach to collagen and factor VIII, but unable to bind platelets
- B: vWF binds to platelets in the bloodstream, without injury. These platelets are cleared by the liver and spleen causing thrombocytopenia
- M: vWF can attach to collagen and factor VIII, but unable to bind platelets
- N: vWF binds to collagen and platelets, but not to factor VIII
Type 3 VWF pathophysiology
rarest and most severe, autosomal recessive, individuals may have no vWF factor!
S + S of VWF
- Easy, prolonged or heavy bleeding e.g.
- Bleeding gums with brushing
- Nose bleeds (epistaxis)
- Heavy menstrual bleeding (menorrhagia)
- Heavy bleeding during surgical operations
Easy bruising
Severe cases:
Joint bleeding
Muscle bleeding
GI bleeding
Investigation and diagnosis of VWF
based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations.
- Platelets count: usually normal except in type IIB
- Prothrombin time: tests the extrinsic and common pathway and so is normal
- Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged
- Measurement of vWF antigen
Management of VWF
- Desmopressin:can be used to stimulates the release of VWF
- VWFcan be infused
- Factor VIIIis often infused along with plasma-derived VWF
- Management of women with heavy periods
What are haemophilia A and B
inherited severe bleeding disorders.
Epidemiology of Haemophilia A and B
Almost exclusively affects males (X-linked recessive)
Aetiology of Haemophilia A and B
- Inherited
- Acquired:
- Liver failure
- Vitamin K deficiency
- Autoimmunity against a clotting factor
- ## Disseminated intravascular coagulation
What happens in haemophilia?
decrease in the amount or function of one or more of the clotting factors which makes secondary haemostasis less effective and allows more bleeding to happen.
Haemophilia A is caused by what?
deficiency in factor VIII.
Mutated genes are called F8 - on X chromosome
Haemophilia B is caused by what?
deficiency in factor IX.
Mutated genes called F9 - X chromosomes
Acquired causes of haemophilia A and B
- Liver failure: as the liver is responsible for many of the clotting factors
- Vitamin K deficiency: as vitamin K is needed by many enzymes to synthesise a lot of the clotting factors
- Autoimmunity against a clotting factor
- Disseminated intravascular coagulation
S + S of Haemophilia
Abnormal bleeding
Excessive Bleeding
- Ecchymosis: easy bruising
- Spontaneous haemorrhage
- Haematomas: collections of blood outside the blood vessels
- Haemoarthrosis: bleeding into joint
What is diagnosis of haemophilia usually based on?
bleeding scores, coagulation factor assays and genetic testing.
- Platelets count: usually normal
- Prothrombin time: tests the extrinsic and common pathway and so is normal
- Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged
Differential diagnosis of haemophilia
- Von Willebrand Disease: can present similarly to haemophilia
- Platelets dysfunction
Treatment of haemophilia
- Avoid contact sports and medicines that promote bleeding e.g. aspirin
- IV infusion of deficient clotting factor (either prophylactic or in response to bleeding)
- Complication: if patients initially had very low levels of the clotting factor, the immune system might mount an attack against the IV clotting factors, potentially leading to anaphylaxis
- Desmopressin: to stimulate the release of von Willebrand Factor
- Antifibrinolytics e.g. tranexamic acid
complications of haemophilia
- Bleeds into the brain are a dangerous complication: can cause a stroke or increased intracranial pressure
- Haemarthrosis: can cause problems with joints
What is Disseminated intravascular coagulation (DIC)
acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.
Out of control clotting - leads to thrombus and reduction of platelets
What does DIC describe
a situation in which the process of haemostasis starts to run out of control.
Pathophysiology of DIC
Pathology (sepsis, trauma, malignanacy) causes release of procoagulant (eg Tissue Factor) tipping scales for clot formation
Causes blood clots to form leading to ischemia , necrosis and eventually organ damage
