Von Willebrand disease Flashcards
What is Von Willebrand disease?
This is the most common inherited bleeding disorder.
It is due to either a quantitative or qualitative abnormality of Von Willebrand factor (VWF).
What does VWF do?
VMF provides a critical link between platelets and exposed vascular subendothelium, and also binds and stabilises coagulation factor VIII.
VWF protein is synthesised in endothelial cases and megakaryocytes and is secreted as multimers.
How does VWD usually present?
It usually presents with mucocutaneous bleeding.
Menorrhagia and postnatal haemorrhage common in affected females.
Joint bleeding rare and seen only in severe disease.
Aetiology of VWD
VWD is usually due to a mutation in the VWF gene, but the linkage is not seen in approximately 30% of type 1 cases.
Pathophysiology of VWD
Symptoms characteristic of platelet dysfunction, predominantly mucosal bleeding.
Excessive postoperative bleeding.
Symptoms exacerbated by medications such as aspirin that inhibit platelet function.
Classification of VWD
Type 1: partial quantitative deficiency of VWF (>0.6 antigen)
Type 2: qualitative VWF defects (<0.6 antigen)
Type 2A: Decreased VWF-dependent platelet adhesion due to a selective deficiency of high-molecular-weight multimers
Type 2B: increased affinity for platelet glycoprotein Ib
Type 2M: decreased VWF-dependent platelet adhesion without a selective deficiency of high-molecular-weight multimers; it has been suggested that rare patients with decreased collagen-binding activity without a reduction in high-molecular-weight multimers should also be included in this group
Type 2N: markedly decreased binding affinity for factor VIII
Type 3: virtually complete deficiency of VWF
Signs & symtoms of VWD
Easy bruising (T1)
Excessive bleeding from minor wounds (T1)
Mucosal bleeding (T1)
Menorrhagia (T1)
Post-operative bleeding (T1)
Bleeding may begin at an earlier age than T1 (T2/T3)
Signs of anaemia may be present
Investigations of VWD
PT
aPTT
FBC- anaemia and thrombocytopenia
Bleeding test- not sensitive or specific enough for diagnosis.
Further testing:
VWF antigen
VWF activity by ristocetin cofactor and collagen binding.
Differentials of VWD
Mild haemophilia A.
Inherited platelet function disorder.
Treatment of unknown VWD with active severe haemorrhage
First line:
1) VWF concentrates- patients with active severe haemorrhage require resuscitation as appropriate. These patients should be treated as if they have type 3 VWD until more historical and/or laboratory information allows identification of the specific type of VWD. Most VWF concentrates contain both VWF and factor VIII.
2) Platelet transfusion may be useful in the rare patient with continued bleeding despite treatment with von Willebrand factor-containing concentrates.
Treatment of all types VWD with severe bleeding uncontrolled by desmopressin, antifibrinolytics, and VWF-containing concentrate.
1st line:
Platelet transfusion-In patients with bleeding refractory to plasma replacement therapy, platelets are a useful source of von Willebrand factor (VWF), which is released at the site of injury. Platelet VWF is absent in patients with type 3 VWD.
2nd line:
Cryoprecipitate- Used as for factor concentrate, but carries a greater risk of viral transmission.
Treatment of all types VWD with severe bleeding or before high-risk bleeding procedures (including where sustained high levels of VWF required for several days): with or without mucosal involvement.
1) VWF concentrates- patients with active severe haemorrhage require resuscitation as appropriate. These patients should be treated as if they have type 3 VWD until more historical and/or laboratory information allows identification of the specific type of VWD. Most VWF concentrates contain both VWF and factor VIII.
2) Antifibrinolytic therapy: tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.
Treatment of all types VWD with minor bleeding or before procedures: involving mucous membranes.
1) Antifibrinolytic therapy: tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.
2) Desmopressin may be used as an adjunct to antifibrinolytic therapy in patients known to respond to this drug.
What is desmopressin?
It causes the release of VWF and factor VIII from endothelial stores.
All patients with type 1, 2A, or 2M VWD should be tested to see whether they respond to desmopressin unless its use is contraindicated (e.g., patients with atherosclerosis, cardiac insufficiency or other conditions that are treated with diuretics, psychogenic polydipsia, and polydipsia in alcohol dependence).
Treatment of all types VWD with chronic or recurrent menorrhagia
1) Oral hormonal therapy- used to treat menorrhagia where benefits of treatment outweigh any risks. Oestrogen-containing compounds may also be effective in refractory gastrointestinal bleeding, but evidence is anecdotal.
2) Antifibrinolytic therapy: tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.
