vWB Disease and Platelet Function Disorders Flashcards Preview

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Flashcards in vWB Disease and Platelet Function Disorders Deck (18):
1

What is the function of von Willebrand Factor?

Platelet adhesion

Carrier protein for FVII

Angiogenesis

2

Describe the structure of a platelet.

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

3

What are the stages of platelet aggregation?

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

4

What are the bleeding symptoms during the newborn period?

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

5

What are the bleeding symptoms from infancy to school age?

  • 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

6

What are the bleeding symtpoms in adolescents and adults?

  • 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

7

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

  • 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

8

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

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

9

What are some common drugs that can result in bleeding?

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

10

What laboratory evaluations are done for bleeding disorders?

  • 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)

11

What is the epidemiology of vWD?

  • 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

12

What are the types of vWD?

  • 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

13

How is von Willebrand Disease diagnosed?

  • 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

14

How is vWD managed?

  • 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]

15

Describe the classification of platelet disorders.

  • 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

16

What are some key physical exam findings indicating platelet disorders?

  • 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

17

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

  • 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

18

What are some general treatment principles for platelet function disorders?

  • 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