Von Willebrand disease

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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

Differential Diagnosis

Coagulopathy

Platelet Related

Factor Related

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

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.


For major procedures follow factor VIII levels with plan to keep troughs over 80%

Not desmopressin responsive:
Humate-P to achieve peak over 120% and troughs of 80%.

Levels below 30%: 40-50 IU/kg followed by 20 IU/kg every 12 hours

Levels above 30%: 20-40 IU/kg every day

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

Disposition

See Also

References

  1. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease
  2. Humate-P dosing http://www.humate-p.com/DOCS/HumateP-Dosage-PI.pdf