kuliah 6 von willebrand disease (vwd)

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

……