Von Willebrand disease
Revision as of 20:01, 26 July 2016 by Neil.m.young (talk | contribs) (Text replacement - "==Diagnosis==" to "==Evaluation==")
Background
- Most common inherited bleeding disorder
- vWF has two roles:
- 1. Acts as cofactor for platelet adhesion
- 2. Acts as carrier protein for factor VIII extending its half life
- vWD results from quantitative or qualitative dysfunction of Von Willebrand factor
Clinical Features
- Skin and mucosal bleeding
- Epistaxis, gingival bleeding, menorrhagia
- Hemarthrosis is unusual
Differential Diagnosis
Coagulopathy
Platelet Related
- Too few
- Nonfunctional
Factor Related
- Acquired (Drug Related)
- Warfarin (Coumadin)
- Unfractionated heparin
- Low molecular weight heparin (i.e. enoxaparin (Lovenox), dalteparin)
- Factor Xa Inhibitors (e.g. rivaroxaban, apixaban, fondaparinux, edoxaban)
- Direct thrombin inhibitors (e.g. dabigatran, argatroban, bivalirudin)
- Illness induced
- Genetic
Evaluation
- Bleeding time: prolonged
- PT: normal
- PTT: normal-mildly prolonged
- vWF activity level: low
Management
- Avoid ASA, NSAIDs, heparin
Intermediate purity factor VIII
- Goal to increase VWF activity by 50-100%
- Initial infusion of 20-40 IU/Kg
- High replacement doses may be indicated in more severe disease
Platelet transfusion
- Consider if replacement therapy instituted and persistent bleeding
Desmopressin
- Induces release of vWF from endothelial storage sites
- 0.3mcg/kg IV (max 20mcg) over 30min
Aminocaproic acid (Amicar)
- Analogue of the amino acid lysine making it an inhibitor for proteolytic enzymes like plasmin, the enzyme responsible for fibrinolysis.
Recombinant Factor VIIa
- Consider in type 3 VWD patients who have developed antibodies to VWF replacement
- Increased risk of thrombosis, especially in patients with coronary artery disease
Types of Von Willebrand Disease | Pathophysiology | Therapy | Procedures |
Type 1 | Low levels of all proteins | Desmopressin | Desmopressin Responsive: Infuse 0.3 ug/kg to end 45 minutes before procedure. May repeat every 24 hours.
|
Type 2 | Abnormal protein | ||
Type 2A | Abnormal protein leading to lower levels of high weight multimers | Desmopressin (only effective in 10%), Humate-P | |
Type 2B | Abnormal protein with increased binding to gpIIb leading to lower levels of high weight multimers | Humate-P | |
Type 2N | Lack of Factor VIII binding site leading to low Factor VIII levels | Desmopressin | |
Type 2M | Abnormal protein but normal multimer size | Humate-P | |
Type 3 | No von Willebrand or Factor VIII present | Humate-P | |
Pseudo Von Willebrand (platelet-type) | Abnormal gpIIb leading to lower levels of high molecular weight multimers | Platelets + Humate-P, rVIIa |
See Also
References
- Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease