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von Willebrand Disease (VWD)von Willebrand Disease (VWD)
Rosita Juwita Sembiring
Frequency of Hereditary Bleeding Frequency of Hereditary Bleeding DisordersDisorders
1/100
1/10,000
1/50,000
1-10/1,000,000*
von Willebrandvon Willebrand 1/100
1/100,000,000
1/500,000,000
1/100,000
N/A
1/1/100,000,000
1/1/500,000,000
N/A
MaleMale FemaleFemaleSymptomaticSymptomaticFemale CarrierFemale Carrier
Hemophilia AHemophilia A
Hemophilia BHemophilia B
Factor XIFactor XI
*In some populations 1/10,000 or less (1/500 for Ashkenazi Jews)
Evaluation of the Bleeding PatientEvaluation of the Bleeding Patient
Patient’s history
Family history
Physical findings
Laboratory evaluation
Evaluation of the Bleeding PatientEvaluation of the Bleeding Patient
Type and extent of bleeding (eg, mucous membrane bleeding, petechiae, hemarthrosis, severity, etc.)
Past history of bleeding, surgery, dental extractions
Family history of bleeding disorder, autoimmune disease
Underlying diseases (eg, liver disease, renal failure, malabsorption syndrome, sepsis, SLE)
Symptoms of Symptoms of von Willebrand Disease (VWD)von Willebrand Disease (VWD)
Nose bleeds (epistaxis)
Gum bleeds (gingival bleeding)
Excessive bruising
Gastrointestinal bleeding
Bleeding following tooth extraction
Post-operative bleeding
Heavy periods (menorrhagia)
Postpartum hemorrhage
Heavy bleeding following cuts
Characteristics of “Classic” Characteristics of “Classic” (Type 1) von Willebrand Disease(Type 1) von Willebrand Disease
Prolonged BT
FVIII, R: Co, and VWF: Ag are proportionately decreased
Diagnostic Tests for Suspected Diagnostic Tests for Suspected von Willebrand Disease von Willebrand Disease
FVIII
Ristocetin cofactor assay (R:Co) *
von Willebrand factor antigen (VWF:Ag)
Bleeding time (BT)
*The ristocetin cofactor assay measures VWF
activity
Historical Diagnosis ofHistorical Diagnosis ofvon Willebrand Diseasevon Willebrand Disease
Prolonged bleeding time with normal platelet count
Autosomal dominant mode of inheritance
Type 1 VWDType 1 VWD
most common type of VWD - 70-80%
reduced VWF:Ag and VWF:RCo in parallel
often, PTT and BT are normal
VWF multimers are normal, but reduced concentration
very common genetic defect - up to 1-2% of population
inheritance is usually autosomal dominant, occ. recessive
Treatment:
DDAVP is treatment of choice !
VWF concentrate reserved for those unresponsive
decreased VWF protein, sometimes reduced mRNA
to DDAVP or if intensive treatment is requiredVSD
VSD
NP
TTP
type 2
Aty
pe 2
Bty
pe 1
type 3
VWF:Ag 32 u/dl
VWF:RCo31 u/dl
FVIII 63 u/dl
C
Types of Types of von Willebrand Diseasevon Willebrand Disease
Type I: quantitative - normal multimers but decreased amounts
Type 2: qualitative abnormality in VWF
– 2A: absence of (the hemostatically most effective) large multimers of VWF
– 2B: the large multimers of VWF are abnormal, having a heightened affinity for platelets
Type 3: severe form of VWD- extremely low levels of VWF and FVIII
What is Hemophilia?
Hemophilia is an inherited bleeding disorder in which there is a deficiency or lack of factor VIII (hemophilia A) or factor IX (hemophilia B)
Types of Bleeding Disorders Hemophilia A (factor VIII deficiency)
Hemophilia B (factor IX deficiency)
Incidence
Hemophilia A: 1:5000 male births
Hemophilia B: 1:30,000 male births
Coagulation Cascade
Hoffman et al. Hoffman et al. Blood Coagul FibrinolysisBlood Coagul Fibrinolysis 1998;9(suppl 1):S61. 1998;9(suppl 1):S61.
TF-Bearing CellTF-Bearing Cell
Activated PlateletActivated Platelet
PlateletPlatelet
TFTF
VIIIaVIIIa VaVa
VIIIaVIIIa VaVa
VaVa
VIIaVIIa
TFTF VIIaVIIa XaXa
XX IIIIIIaIIa
IXIXVV VaVa
IIII
VIII/vWFVIII/vWF
VIIIaVIIIa
IIII
IXaIXa
XXIXIX
XX
IXaIXa
IXaIXaVIIaVIIaXaXa
IIaIIa
IIaIIa
XaXa
Inheritance
Hemophilia A and B are X-linked recessive disorders Hemophilia is typically expressed in males and
carried by females Severity level is consistent between family members 30 % of cases of hemophilia are new mutations Affects all races and ethnic groups equally Moderate & mild deficiencies under-diagnosed
Genetics Affected males
– All daughters are carriers– No sons are affected
Female carrier– 50% risk for carrier daughter– 50% risk for affected son
Type and Severity
Normal factor VIII or IX level 50-150%
Mild hemophilia– factor VIII or IX level 5-50%
Moderate hemophilia– factor VIII or IX level 1-5%
Severe hemophilia– factor VIII or IX level <1%
First Bleed/Diagnosis
Mild– Often has bleeds at an earlier age but not
identified till later in life, 3 to 14 years or older
Moderate– usually before 2 years
Severe– within first year
Bleeding Pattern Mild
Once a year Joint and muscle bleed unusual except
with significant trauma Trauma-induced or contact sports:
significant hematomas Internal deep bleeding only with significant
trauma Post op bleeding
Carriers
Carriers may have low factor levels Carriers may experience bleeding
symptoms seen in mild or moderate deficient states
Treat carriers as potential bleeders
Bleeding Pattern Moderate
Bleeds once a month Minor trauma causes joint and muscle bleed may have target joints Post surgical: wound hematoma or oozing
Bleeding Pattern Severe
Bleeds once a week Spontaneous joint and muscle bleed “Target joints”
Types of Bleeds
Joint bleeding - hemarthrosis
Muscle hemorrhage
Soft tissue
Life threatening-bleeding
Other common bleeding
Joint or Muscle Bleeding
Symptoms– Tingling or bubbling sensation– Stiffness– Warmth– Pain– Unusual limb position
Treatment of Hemophilia
Replacement of missing clotting protein Intravenous infusion– On demand– Prophylaxis Primary/Secondary
Factor VIII Concentrate
Intravenous infusion– IV push
Dose varies depending on type of bleeding– Ranges from 20-50+ units/kg. body weight
Half-life 8-12 hours Each unit infused raises serum factor VIII
level by 2 %
Adjunctive Therapy
RICE– Rest /Replacement – Ice/Immobilization– Compression– Elevation
Antifibrinolytic Agents– Amicar ® (aminocaproic acid)
Used for mucocutaneous bleedingDosing: 50 mg./kg. q. 6 hours po
Advanced Joint Bleed
Advanced joint and muscle bleed
Hemophilia Treatment Center Team Members
Patient / Family
Hematologist Pediatric
Adult
Nurse
Social Worker
Physical Therapist
Orthopedist
Primary Care
Genetics
Home Care
Company
Dental
……