Updated: 9/23/2018

Von Willebrand Disease

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.Snapshot
  • A 25-year-old woman presents to the emergency room with prolonged bleeding after a dental procedure early that day. She has gone through several gauze packing with no success. Her past medical history includes heavy and prolonged menses. As a child, she had several episodes of unexplained nosebleeds. Labs show normal PT, PTT, and platelet count.
Introduction

This illustration depicts the basic mechanism behind platelet aggregation. This image is also integrated with pathology and pharmacology that alters this cascade of events. vWF = von Willebrand factor; TXA2 = Thromboxane A2; COX = Cyclooxygenase.

  • Inherited mixed platelet and coagulation disorder from deficiency in von Willebrand factor (vWF)
  • Genetics
    • autosomal dominant
  • Epidemiology
    • most common inherited bleeding disorder
    • more likely in Caucasians
  • Pathogenesis
    • affects coagulation - vWF carries and protects factor VIII 
      • produced by endothelial cells and megakaryocytes
      • intrinsic pathway coagulation defect
    • affects platelets – vWF is important in platelet adherence to endothelial lining
      • platelet aggregation is normal (mediated by fibrinogen)
Presentation
  • Symptoms
    • mucocutaneous bleeding
      • epistaxis
      • gingival bleeding
      • petechiae
      • easy bruising
      • menorrhagia
    • increased bleeding after aspirin use
Evaluation
  • Normal or ↑ PTT (like hemophilia) 
  • Normal PT
  • ↑ bleeding time (unlike hemophilia)
  • CBC
    • normal platelet count and appearance
    • may have anemia
  • Diagnosis by ristocetin cofactor assay
    • tests ability of platelets to bind to ristocetin (artificial endothelial surface)
    • ↓ platelet agglutination
Differential Diagnosis
  • Bernard-Soulier syndrome
  • Glanzmann thrombasthenia
  • Hemophilia
Treatment
  • DDAVP (desmopressin acetate) 
    • releases vWF stored in endothelial cells
  • Factor VIII replacement if refractory to DDAVP
    • contains vWF
Prognosis, Prevention, and Complications
  • Prognosis
    • most are mild or moderate in severity
  • Prevention
    • avoid aspirin
  • Complications
    • excessive bleeding
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
Calculator

(M1.HE.4707) A 16-year-old male presents to the emergency department with a hematoma after falling during gym class. He claims that he has a history of prolonged nosebleeds and bruising/bleeding after minor injuries. Physical exam is unrevealing other than the hematoma. Labs are obtained showing an increased bleeding time and an abnormal ristocetin cofactor assay. Coagulation assays reveal an increased partial thromboplastin time (PTT) and but a normal prothrombin time (PT). The patient is given desmopressin and is asked to avoid aspirin. Which of the following findings is most likely directly involved in the etiology of this patient's presentation? Review Topic

QID: 108426
1

Decreased platelet count

9%

(25/291)

2

Decreased levels of factor VIII

62%

(181/291)

3

Decreased levels of factor IX

7%

(21/291)

4

Decreased activity of ADAMTS13

13%

(37/291)

5

Decreased plasma fibrinogen

5%

(14/291)

M1

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