Von Willebrand disease
(Redirected from Von Willebrand Disease (vWD))
Background
- Abbreviation: vWD
- Most common inherited bleeding disorder[1]
- 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 (more common in factor deficiencies)
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
- Platelet count: normal
- Bleeding time: prolonged
- PT: normal
- PTT: normal-mildly prolonged
- vWF activity level: low
Management
- Avoid ASA, NSAIDs, heparin and coordinate with hematology prior to any invasive or surgical procedures.
- Multiple therapeutic options exist for prophylaxis or treatment of bleeding. The majority of therapy utilizes Humate-P and/or desmopressin
Humate-P
VWF and factor VIII concentration is the first line therapy for vWD bleeding patients. It is contraindicated for any patient with prior history of anaphylaxis to Humate-p
- Loading dose 40 to 60 IU/kg, then 40 to 50 IU/kg every 8 to 12 hours for 3 days to keep the trough level of VWF:RCo >50%; then 40 to 50 IU/kg daily for a total of up to 7 days of treatment. [2]
- For severe bleeding the loading dose is increased to 50 to 75 IU/kg
Type of Hemorrhages/Surgery | Loading Dosage (IU VWF:RCo/ kg BW) | Maintenance Dosage (IU VWF:RCo/ kg BW) | Therapeutic Goal |
Minor Hemorrhages | 20-40 IU/kg | 20-30 IU/kg every 12-24 hours | VWF:RCo and FVIII activity trough levels of >30% |
Major Hemorrhages | 40-60 IU/kg | 20-40 IU/kg every 12-24 hours | VWF:RCo and FVIII activity trough levels of >50% |
Minor Surgeries | 30-60 IU/kg | 15-30 IU/kg or half the loading | VWF:RCo peak level of 50% after loading dose |
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%), Intermediate-Purity Factor VIII | |
Type 2B | Abnormal protein with increased binding to gpIIb leading to lower levels of high weight multimers | Intermediate-Purity Factor VIII | |
Type 2N | Lack of Factor VIII binding site leading to low Factor VIII levels | Desmopressin | |
Type 2M | Abnormal protein but normal multimer size | Intermediate-Purity Factor VIII | |
Type 3 | No von Willebrand or Factor VIII present | Intermediate-Purity Factor VIII | |
Pseudo Von Willebrand (platelet-type) | Abnormal gpIIb leading to lower levels of high molecular weight multimers | Platelets + Intermediate-Purity Factor VIII, rVIIa |
Disposition
See Also
References
- ↑ Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease
- ↑ Humate-P dosing http://www.humate-p.com/DOCS/HumateP-Dosage-PI.pdf