Von Willebrand disease: Difference between revisions
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==Background==
==Background==
*Abbreviation: vWD
*Most common inherited bleeding disorder<ref>Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease </ref>
*Most common inherited bleeding disorder<ref>Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease </ref>
*vWF has two roles:
*vWF has two roles:
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*Avoid ASA, NSAIDs, heparin and coordinate with hematology prior to any invasive or surgical procedures.
*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]]
*Multiple therapeutic options exist for prophylaxis or treatment of bleeding.  The majority of therapy utilizes Humate-P and/or [[desmopressin]]
===Humate-p===
 
''Contraindicated for any patient with prior history of anaphylaxis to Humate-p''
===Intermediate-Purity Factor VIII===
====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. <ref> Humate-P dosing http://www.humate-p.com/DOCS/HumateP-Dosage-PI.pdf</ref>
*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. <ref> Humate-P dosing http://www.humate-p.com/DOCS/HumateP-Dosage-PI.pdf</ref>
*For severe bleeding the loading dose is increased to 50 to 75 IU/kg
*For severe bleeding the loading dose is increased to 50 to 75 IU/kg


===Intermediate purity factor VIII===
====Wilate====
*Goal to increase VWF activity by 50-100%
{| {{table}}
*Initial infusion of 20-40 IU/Kg
| align="center" style="background:#f0f0f0;"|'''Type of Hemorrhages/Surgery'''
*High replacement doses may be indicated in more severe disease
| align="center" style="background:#f0f0f0;"|'''Loading Dosage (IU VWF:RCo/ kg BW)'''
| align="center" style="background:#f0f0f0;"|'''Maintenance Dosage (IU VWF:RCo/ kg BW)'''
| align="center" style="background:#f0f0f0;"|'''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===
===Platelet transfusion===
*Consider if replacement therapy instituted and persistent bleeding
*Consider if replacement therapy instituted and persistent bleeding
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| Type 2 ||Abnormal protein ||
| Type 2 ||Abnormal protein ||
|-
|-
| Type 2A ||Abnormal protein leading to lower levels of high weight multimers ||Desmopressin (only effective in 10%), Humate-P
| 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 ||Humate-P
| 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 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 2M ||Abnormal protein but normal multimer size ||Intermediate-Purity Factor VIII
|-
|-
| Type 3 ||No von Willebrand or Factor VIII present ||Humate-P
| 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 + Humate-P, rVIIa  
| 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==
==See Also==

Revision as of 21:03, 27 June 2017

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

Intermediate-Purity Factor VIII

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

Wilate

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.


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%), 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

  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
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