Von Willebrand Factor disease: Difference between revisions
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Von Willebrand Factor disease
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− | == |
+ | ==Background== |
− | * |
+ | *Deficiency in quantity or quality of von Willebrand Factor (vWF) increasing risk of bleeding |
+ | ===Classification=== |
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− | == Type == |
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− | * |
+ | *Type 1 (80%): mild quantitative deficiency |
− | * |
+ | *Type 2 (20%): qualitative deficiency (i.e. doesn't work properly) |
− | ** |
+ | **Type 2A: normal quantity, abnormal quality |
− | ** |
+ | **Type 2B: enhanced GP1b-binding, leading to platelet adhesion and clearance |
− | ** |
+ | **Type 2M, Type 2N |
− | * |
+ | *Type 3 (<1%): autosomal-recessive absolute quantitative deficiency (i.e. none made) |
− | * |
+ | *Acquired: vWF cleared by autoantibodies, sheared by aortic stenosis, or sequestered by thrombocytosis |
+ | ===Pathophysiology=== |
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− | == Physiology == |
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− | * |
+ | *vWF is long multimer that helps platelet aggregation in response to endothelial damage |
− | * |
+ | *vWF is released by endothelium in response to damage |
− | * |
+ | *vWF binds Factor VIII as well as platelets |
− | * |
+ | *It unravels, thereby exposing platelet binding sites |
− | == |
+ | ===Epidemiology=== |
− | * |
+ | *Most common bleeding disorder with a prevalence of 1 in 100 |
− | * |
+ | *Prevalence of significant bleeding is 1 in 10,000 |
+ | *Most are inherited in autosomal dominant pattern (including types 1 and 2B and most 2A and 2M), though type 2N and 3, and some type 2A and 2M, are autosomal recessive |
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− | == |
+ | ==Clinical Manifestations== |
+ | * Abnormal bleeding |
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+ | |||
+ | {| class="wikitable" |
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− | !align="center" |
+ | ! align="center" |'''vWF-Ag''' |
− | !align="center" |
+ | ! align="center" |'''vWF-RCo''' |
− | !align="center" |
+ | ! align="center" |'''FVIII''' |
− | !align="center" |
+ | ! align="center" |'''RIPA''' |
− | !align="center" |
+ | ! align="center" |'''Multimers''' |
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|- |
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− | | |
+ | |'''Type 1''' |
− | |align="center" |
+ | | align="center" |↓ |
− | |align="center" |
+ | | align="center" |↓ |
− | |align="center" |
+ | | align="center" |↓ |
− | |align="center" |
+ | | align="center" |↓ |
− | |align="center" |
+ | | align="center" |N |
|- |
|- |
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− | | |
+ | |'''Type 2A''' |
− | |align="center" |
+ | | align="center" |↓/N |
− | |align="center" |
+ | | align="center" |↓↓ |
− | |align="center" |
+ | | align="center" |↓/N |
− | |align="center" |
+ | | align="center" |↓↓ |
− | |align="center" |
+ | | align="center" |Lack of HMWM |
|- |
|- |
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− | | |
+ | |'''Type 2B''' |
− | |align="center" |
+ | | align="center" |↓/N |
− | |align="center" |
+ | | align="center" |↓ |
− | |align="center" |
+ | | align="center" |↓/N |
− | |align="center" |
+ | | align="center" |↑ |
− | |align="center" |
+ | | align="center" |Lack of HMWM |
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|- |
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− | | |
+ | |'''Type 2M''' |
− | |align="center" |
+ | | align="center" |N |
− | |align="center" |
+ | | align="center" |↓↓ |
− | |align="center" |
+ | | align="center" |N |
− | |align="center" |
+ | | align="center" |↓↓ |
− | |align="center" |
+ | | align="center" |N |
|- |
|- |
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− | | |
+ | |'''Type 2N''' |
− | |align="center" |
+ | | align="center" |N |
− | |align="center" |
+ | | align="center" |N |
− | |align="center" |
+ | | align="center" |↓ |
− | |align="center" |
+ | | align="center" |N |
− | |align="center" |
+ | | align="center" |N |
|- |
|- |
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− | | |
+ | |'''Type 3''' |
− | |align="center" |
+ | | align="center" |Absent |
− | |align="center" |
+ | | align="center" |Absent |
− | |align="center" |
+ | | align="center" |0.05 u/mL |
− | |align="center" |
+ | | align="center" |Absent |
− | |align="center" |
+ | | align="center" |Absent |
|} |
|} |
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− | == |
+ | ==Management== |
− | * |
+ | *For Type 1 and 2A |
− | ** |
+ | **[[Desmopressin]] (ddAVP) 0.3mg/kg (max 20mg) IV/SC can promote release of vWF from endothelium |
− | ** |
+ | **Lasts 8-12h, so can repeat q12-24h as long as needed |
− | ** |
+ | **Monitor for tachyphylaxis after 4 doses |
{{DISPLAYTITLE:von Willebrand Factor disease}} |
{{DISPLAYTITLE:von Willebrand Factor disease}} |
Revision as of 22:50, 19 November 2020
Background
- Deficiency in quantity or quality of von Willebrand Factor (vWF) increasing risk of bleeding
Classification
- Type 1 (80%): mild quantitative deficiency
- Type 2 (20%): qualitative deficiency (i.e. doesn't work properly)
- Type 2A: normal quantity, abnormal quality
- Type 2B: enhanced GP1b-binding, leading to platelet adhesion and clearance
- Type 2M, Type 2N
- Type 3 (<1%): autosomal-recessive absolute quantitative deficiency (i.e. none made)
- Acquired: vWF cleared by autoantibodies, sheared by aortic stenosis, or sequestered by thrombocytosis
Pathophysiology
- vWF is long multimer that helps platelet aggregation in response to endothelial damage
- vWF is released by endothelium in response to damage
- vWF binds Factor VIII as well as platelets
- It unravels, thereby exposing platelet binding sites
Epidemiology
- Most common bleeding disorder with a prevalence of 1 in 100
- Prevalence of significant bleeding is 1 in 10,000
- Most are inherited in autosomal dominant pattern (including types 1 and 2B and most 2A and 2M), though type 2N and 3, and some type 2A and 2M, are autosomal recessive
Clinical Manifestations
- Abnormal bleeding
Investigations
- CBC, PT/INR, PTT
- vWD screen: Factor VIII, vWF antigen, vWF activity (either ristocetin cofactor or collagen)
- Consider PFA-100 (in-vitro bleeding time) and blood type
- If suspecting Type 2:
- RIPA (ristocetin-induced platelet agglutination)
- Multimer studies for high molecular weight multimers (MHWM)
- vWF genetic testing
vWF-Ag | vWF-RCo | FVIII | RIPA | Multimers | |
---|---|---|---|---|---|
Type 1 | ↓ | ↓ | ↓ | ↓ | N |
Type 2A | ↓/N | ↓↓ | ↓/N | ↓↓ | Lack of HMWM |
Type 2B | ↓/N | ↓ | ↓/N | ↑ | Lack of HMWM |
Type 2M | N | ↓↓ | N | ↓↓ | N |
Type 2N | N | N | ↓ | N | N |
Type 3 | Absent | Absent | 0.05 u/mL | Absent | Absent |
Management
- For Type 1 and 2A
- Desmopressin (ddAVP) 0.3mg/kg (max 20mg) IV/SC can promote release of vWF from endothelium
- Lasts 8-12h, so can repeat q12-24h as long as needed
- Monitor for tachyphylaxis after 4 doses