Von Willebrand disease: Difference between revisions

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==Background==
==Background==
*Most common inherited bleeding disorder
*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>
*vWF has two roles:
*vWF has two roles:
**1. Acts as cofactor for platelet adhesion
**1. Acts as cofactor for platelet adhesion
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==Clinical Features==
==Clinical Features==
*Skin and mucosal bleeding
*Skin and mucosal bleeding
**Epistaxis, gingival bleeding, menorrhagia
**[[Epistaxis]], gingival bleeding, [[vaginal Bleed Non-Pregnant|menorrhagia]]
*Hemarthrosis is unusual
*Hemarthrosis is unusual


==Differential Diagnosis==
==Differential Diagnosis==
{{Increased bleeding DDX}}


==Diagnosis==
==Evaluation==
*Platelet count: normal
*Bleeding time: prolonged
*Bleeding time: prolonged
*PT: normal
*PT: normal
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*vWF activity level: low
*vWF activity level: low


==Treatment==
==Management==
*Avoid ASA, NSAIDs, heparin
*Avoid [[ASA]], [[NSAIDs]], [[heparin]] and coordinate with hematology prior to any invasive or surgical procedures.
*Intermediate purity factor VIII
*Multiple therapeutic options exist for prophylaxis or treatment of bleeding.  The majority of therapy utilizes Humate-P and/or [[desmopressin]]
**Goal to increase VWF activity by 50-100%
 
**Initial infusion of 20-40 IU/Kg
===[[Humate-P]]===
**High replacement doses may be indicated in more severe disease
''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''
*Platelet transfusion
*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>
**consider if replacement therapy instituted and persistent bleeding
*For severe bleeding the loading dose is increased to 50 to 75 IU/kg
*Desmopressin
 
**Induces release of vWF from endothelial storage sites
{| {{table}}
**0.3mcg/kg  IV (max 20mcg) over 30min
| align="center" style="background:#f0f0f0;"|'''Type of Hemorrhages/Surgery'''
*Aminocaproic acid
| align="center" style="background:#f0f0f0;"|'''Loading Dosage (IU VWF:RCo/ kg BW)'''
*Recombinant Factor VIIa
| align="center" style="background:#f0f0f0;"|'''Maintenance Dosage (IU VWF:RCo/ kg BW)'''
**Consider in type 3 VWD patients who have developed antibodies to VWF replacement
| align="center" style="background:#f0f0f0;"|'''Therapeutic Goal'''
**Increased risk of thrombosis, especially in patients with coronary artery disease
|-
| 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
 
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Types of Von Willebrand Disease'''
| align="center" style="background:#f0f0f0;"|'''Pathophysiology'''
| align="center" style="background:#f0f0f0;"|'''Therapy'''
| align="center" style="background:#f0f0f0;"|'''Procedures'''
|-
| Type 1 ||Low levels of all proteins ||Desmopressin ||rowspan="8"|'''Desmopressin Responsive:''' <br>Infuse 0.3 ug/kg to end 45 minutes before procedure. May repeat every 24 hours.
<br>For major procedures follow factor VIII levels with plan to keep troughs over 80%<br> <br>'''Not desmopressin responsive:'''<br>Humate-P to achieve peak over 120% and troughs of 80%.<br><br>  Levels below 30%: 40-50 IU/kg followed by 20 IU/kg every 12 hours<br><br>Levels above 30%: 20-40 IU/kg every day <br>
|-
| 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==
*[[Coagulopathy (Main)]]


==References==
==References==
*Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease
<references/>
 
[[Category:Heme/Onc]]
[[Category:Heme/Onc]]

Revision as of 19:35, 1 October 2019

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

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
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