Difference between revisions of "Von Willebrand disease"

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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
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**[[Epistaxis]], gingival bleeding, [[vaginal Bleed Non-Pregnant|menorrhagia]]
 
*Hemarthrosis is unusual
 
*Hemarthrosis is unusual
  
==Diagnosis==
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==Differential Diagnosis==
 +
{{Increased bleeding DDX}}
 +
 
 +
==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
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*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
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===[[Humate-P]]===
**High replacement doses may be indicated in more severe disease
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''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
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*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
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| align="center" style="background:#f0f0f0;"|'''Type of Hemorrhages/Surgery'''
*Aminocaproic acid
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| align="center" style="background:#f0f0f0;"|'''Loading Dosage (IU VWF:RCo/ kg BW)'''
*Recombinant Factor VIIa
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| 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
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| align="center" style="background:#f0f0f0;"|'''Therapeutic Goal'''
**Increased risk of thrombosis, especially in patients with coronary artery disease
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|-
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| Minor Hemorrhages||20-40 IU/kg||20-30 IU/kg every 12-24 hours||VWF:RCo and FVIII activity trough levels of >30%
 +
|-
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| 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}}
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| align="center" style="background:#f0f0f0;"|'''Types of Von Willebrand Disease'''
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| align="center" style="background:#f0f0f0;"|'''Pathophysiology'''
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| align="center" style="background:#f0f0f0;"|'''Therapy'''
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| align="center" style="background:#f0f0f0;"|'''Procedures'''
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|-
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| 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>
 +
|-
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| Type 2 ||Abnormal protein ||
 +
|-
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| Type 2A ||Abnormal protein leading to lower levels of high weight multimers ||Desmopressin (only effective in 10%), Intermediate-Purity Factor VIII
 +
|-
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| 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
 +
|-
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| 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
 +
|-
 +
|}
  
==Source==
+
==Disposition==
Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 230. Hemophilias and Von Willebrand Disease
 
  
Uptodate
+
==See Also==
 +
*[[Coagulopathy (Main)]]
  
 +
==References==
 +
<references/>
 
[[Category:Heme/Onc]]
 
[[Category:Heme/Onc]]

Latest 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