vWB Disease and Platelet Function Disorders

Question 1

What is the function of von Willebrand Factor?

Answer 1

Platelet adhesion

Carrier protein for FVII

Angiogenesis

Question 2

Describe the structure of a platelet.

Answer 2

• Peripheral zone
  
  • Outer membrane
• Membrane zone
  
  • Dense tubular system
• Sol-gel-zone
  
  • Microtubules, microfilaments
• Organelle zone
  
  • Granules, mitochondria

Question 3

What are the stages of platelet aggregation?

Answer 3

• Transformation of inactivated platelets to activated platelets & formation of platelet plug:
  
  • Adhesion
  • Aggregation
  • Secretion
  • Contraction

Question 4

What are the bleeding symptoms during the newborn period?

Answer 4

• Bleeding from:
  
  • heel stick,
  • circumcision,
  • injection
  • umbilical cord
• Cephalhematoma
• Subgaleal bleed
• Bruises (trauma from birthing process)
• ICH

Question 5

What are the bleeding symptoms from infancy to school age?

Answer 5

• Bruising (common, from trauma)
• Epistaxis (abnormal unless proven otherwise)
• Hematoma
• Bleeding after shots
• Frenulum bleed
• Muscle bleeding
• Joint bleeding
• Bleeding after minor trauma
• Post-surgical bleed:
• T & A, dental extraction

Question 6

What are the bleeding symtpoms in adolescents and adults?

Answer 6

• Bruising (from sports and other trauma)
• Epistaxis (very common)
• Menorrhagia
• Post-partum bleeding (especially if no breast feeding)
• Joint bleeding
• Muscle bleeding
• Bleeding from:
  
  • Surgical site
  • Dental extractions

Question 7

What are some important points of the history regarding bleeding disorders?

Answer 7

• Epistaxis
  
  • frequency per week or month
  • duration (20+ min is significant)
  • methods to stop event
  • associated anemia
  • ENT referral / intervention
• Menorrhagia (often runs in the family)
  
  • # of pads or tampons per day
  • length of menses
  • need for iron therapy & blood transfusion
  • evaluation by a specialist
  • hormonal intervention
  • surgical intervention
• Assess bleeding history of other family members

Question 8

What are some important past medical history points for disorders of hemostasis?

Answer 8

• Circumcision
• Dental extraction
• T & A
• Labor and delivery
• Any other surgeries
• Be careful while evaluating minor surgeries as they might be uneventful

Question 9

What are some common drugs that can result in bleeding?

Answer 9

• Platelet Antagonists
  
  • Aspirin (irreversible cyclo-oxygenase inhibition)
  • NSAIDS
  • Alcohol
  • Antihistamines (esp. Robutussin)
  • Beta blockers
  • Nitrates
  • Calcium blockers
  • Others:
    
    • LMWH
    • coumadin
    • antidepressants
    • anticonvulsants
    • cephalosporins

Question 10

What laboratory evaluations are done for bleeding disorders?

Answer 10

• Primary hemostasis
  
  • CBC, platelet count, blood smear
  • Bleeding time/ PFA-100 CT (may overdiagnose, measure clotting with CT scanner, less technical)
  • VWD panel: VWF antigen, VWF activity (VWF: RCO) & FVIII levels
  • Platelet function tests:
    
    • BT/PFA-100
    • Platelet aggregation studies
• Secondary hemostasis
  
  • PT, PTT & TT (can have prolonged PTT in vonWillebrand Disease)

Question 11

What is the epidemiology of vWD?

Answer 11

• Most common bleeding disorder
• Affects 1 / 100 population
• Affects males and females equally
• No racial distinction
• Risk is 50% to each child
• Under-recognized disorder
  
  • Symptoms variable
  • Undiagnosed population is large

Question 12

What are the types of vWD?

Answer 12

• Type I and III are quantitative disorders
  
  • Type I - AD, decreased production, increased clearance of vWD factor
  • Type II - AR, significantly decreased production of vWD
• Type II are qualitative
  
  • ​2A, 2B, 2M, 2N

Question 13

How is von Willebrand Disease diagnosed?

Answer 13

• Relies on:
  
  • a personal history of mucocutaneous bleeding
  • laboratory evaluation consistent with qualitative/quantitative deficiency of VWD
  • family history of excessive bleeding
• Laboratory Diagnosis:
  
  • Immunological tests
    
    • amount of protein: VWF: Ag
  • Functional tests check the ability of VWF to bind
    
    • platelets in the presence of ristocetin: VWF:RCo
    • collagen: VWF:CB
    • FVIII: VWF:FVIII
  • III. To assess multimer patterns
• Diagnosis of VWD is not compete without blood group testing!!​
  
  • Type O blood naturally has lower vWF

Question 14

How is vWD managed?

Answer 14

• Local therapy:
  
  • pressure
  • ice
  • cautery
  • topical thrombin
  • fibrin glue
  • salt-pork (bacon is good!)
• Supportive therapy:
  
  • antifibrinolytics [tranexamic acid, Aminocaproic acid]
  • local thrombin application
  • hormonal therapy
• Systemic therapy:
  
  • DDAVP (mechanism unclear, thought to release vWF from WP bodies)
  • VWF concentrates [plasma derived (Humate-P), recombinant]

Question 15

Describe the classification of platelet disorders.

Answer 15

• Membrane glycoprotein defects
  
  • Bernard Soulier Syndrome [GP Ib-IX]
  • Glanzmann’s Thrombasthenia [GP IIb-IIIa]
• Biochemical defects
  
  • Release defects
  • Storage pool disease
  • Aspirin like defect
• Coagulation factor defects
  
  • Fibrinogen
  • WF

Question 16

What are some key physical exam findings indicating platelet disorders?

Answer 16

• Disorders with a known associated platelet function defect
  
  • Hermansky Pudlak: oculocutaneous albinism
  • Wiskott Aldrich syndrome: eczema
  • Ehlers Danlos syndrome: thin skin with abnormal scarring, lax joints
  • Marfan’s syndrome: arm length, facies, dislocated lens
• Disorders associated with acquired platelet dysfunction
  
  • cardiac disease
  • liver disease
  • renal disease
  • hypersplenism

Question 17

What are some important lab findings that indicate a platelet disorder?

Answer 17

• CBC with peripheral smear → review platelet morphology & number
• Abnormalities on smear which may aid diagnosis
  
  • schistocytes, helmet cell
    
    • microangiopathic process: HUS, TTP
• large platelets, decreased number, normal RBC, WBC
  
  • production defect
  • immune mediated process: ITP, drug induced antibody
• large inclusion granules
  
  • Chediak - Higashi
• large platelets
  
  • Bernard - Soulier and May Heggelin
• small platelets, decreased number
  
  • Wiskott - Aldrich
• gray or washed-out platelets
  
  • Gray Platelet Syndrome
• á Majority of platelet function defects have normal platelet count & morphology
• •Platelet aggregation studies

Question 18

What are some general treatment principles for platelet function disorders?

Answer 18

• Local therapy:
  
  • pressure
  • ice
  • cautery
  • topical thrombin
  • fibrin glue
  • salt-pork
• Supportive therapy:
  
  • Antifibrinolytics [tranexamic acid, Aminocaproic acid]
  • local thrombin application
  • hormonal therapy
• Systemic therapy:
  
  • DDAVP
  • Platelet transfusions
  • VWF concentrates [plasma derived (Humate-P), recombinant]
  • rFVIIa