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    Qualitative Disorder (1) - 1

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    Christyl Jo
    This document describes qualitative platelet disorders, which cause abnormal bleeding despite a normal platelet count. It discusses several types of defects including problems with platelet surface membrane proteins like Bernard-Soulier syndrome and Glanzmann thrombasthenia, disorders of platelet granule release or contents like storage pool deficiencies, and abnormalities in platelet-coagulation protein interactions such as von Willebrand disease. The key clinical findings and distinguishing laboratory test results for each condition are outlined.

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    Qualitative Disorder (1) - 1

    Uploaded by

    Christyl Jo
    42 views27 pages
    This document describes qualitative platelet disorders, which cause abnormal bleeding despite a normal platelet count. It discusses several types of defects including problems with platelet surface membrane proteins like Bernard-Soulier syndrome and Glanzmann thrombasthenia, disorders of platelet granule release or contents like storage pool deficiencies, and abnormalities in platelet-coagulation protein interactions such as von Willebrand disease. The key clinical findings and distinguishing laboratory test results for each condition are outlined.

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    Qualitative Disorder (1)-1

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    This document describes qualitative platelet disorders, which cause abnormal bleeding despite a normal platelet count. It discusses several types of defects including problems with platelet surface membrane proteins like Bernard-Soulier syndrome and Glanzmann thrombasthenia, disorders of platelet granule release or contents like storage pool deficiencies, and abnormalities in platelet-coagulation protein interactions such as von Willebrand disease. The key clinical findings and distinguishing laboratory test results for each condition are outlined.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    42 views27 pages

    Qualitative Disorder (1) - 1

    Uploaded by

    Christyl Jo
    This document describes qualitative platelet disorders, which cause abnormal bleeding despite a normal platelet count. It discusses several types of defects including problems with platelet surface membrane proteins like Bernard-Soulier syndrome and Glanzmann thrombasthenia, disorders of platelet granule release or contents like storage pool deficiencies, and abnormalities in platelet-coagulation protein interactions such as von Willebrand disease. The key clinical findings and distinguishing laboratory test results for each condition are outlined.

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    © All Rights Reserved
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    Download as ppt, pdf, or txt
    of 27

    Qualitative

    Platelet Disorders
    Objectives
    • Describe the defects in Bernard Soulier
    Syndrome and Glanzmann Thrombasthenia.
    • Understand the laboratory findings for the
    qualitative platelet disorders.
    • Learn about the storage pool disorders.
    • Compare the von Willebrand Disease to
    Bernard Soulier Syndrome.
    Platelet Function

    Figure 45-07.   Scanning electron micrograph of resting (A) and activated (B) platelets.
    Platelet Action
    Qualitative Defects
    • May be either:
    1. Congenital
     Platelet surface
    membrane defects
     Platelet release or
    secretion defects
     Platelet coagulant activity
    defects
     Defects associated with
    abnormal platelet-
    coagulant protein
    interactions
    2. Acquired

    Graphic accessed URL http://www.accessmedicine.com/loadBinary.aspx?name=licha&filename=licha_IV.A.018.jpg, 2008.


    Qualitative Platelet Disorders Summary:
    Clinical Presentation & Lab Findings

     Bleeding
    Similar to what is seen with
    thrombocytopenic disorders

     Lab Screen Results


     Similar to what is seen with thrombocytopenic
    disorders EXCEPT the platelet count is normal
     Bleeding Time – prolonged
     Platelet count– normal

     Special platelet function tests discriminate


    the nature of the defect
    Congenital Qualitative Defects
    CLASSIFICATIONS:

     Platelet surface membrane defects


    Platelet release or secretion defects
    Platelet coagulant activity defects
    Defects associated with abnormal platelet-
    coagulant protein interactions
    PLATELET SURFACE
    MEMBRANE DEFECTS
    Bernard Soulier Syndrome
    (Giant Platelet Syndrome)
     Adhesion defective
     Inherited in autosomal recessive
    pattern
     Consanguinity often noted in
    affected families
     Missing or defective GP Ib/IX
    receptor
     Usually undetectable vWF
     Thus cannot bind what? Giant platelets in Bernard-Soulier
    syndrome (peripheral blood, ×1000).
     Clinical findings (Modified from Carr JH, Rodak BF:
    Clinical Hematology Atlas, 2nd ed.
     Usually present with abnormal Philadelphia: Saunders, 2004.)
    bleeding in childhood
     Severity variable, but may require
    transfusion and hormonal control
    of menses in females

    Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.


    Bernard Soulier Syndrome
    • Laboratory Findings
    – Mild to moderate thrombocytopenia common
    – Platelets appear large on blood films
    – Platelet aggregation studies
    – Normal platelet aggregation in response to ADP, collagen,
    and epinephrine
    – Absent aggregation in response to ristocetin and vWF
    Glanzmann Thrombasthenia
     Platelet aggregation
    defective What is the significance
    of a deficiency of this
     Inherited in autosomal receptor?
    recessive pattern ** Platelets are unable to aggregate
     Consanguinity often
    noted in affected families

     Missing or defective
    GPIIb/IIIa complex
    Glanzmann Thrombasthenia
    • Clinical presentation
    – Purpura and epistaxis are the most frequent
    types of bleeding, especially in children
    – Bleeding may decrease with age
    – Great variability in bleeding even within
    kindred (family)

    • Laboratory findings
    – Platelet count and morphology are normal
    Glanzmann Thrombasthenia
    Laboratory Findings:

    •Normal platelet count and morphology


    •Poor in vitro clot retraction
    •Prolonged bleeding time
    •Absent platelet aggregation to ADP, thrombin, collagen,
    and epinephrine
    •Normal platelet aggregation to ristocetin
    •Flow cytometric assessment to GPIIb/IIIa revealing
    absence or deficiency
    PLATELET RELEASE OR
    SECRETION DEFECTS
    • Storage Pool Deficiencies (Granule Defects)
    • Primary Secretion Defects
    Storage Pool Disorders
    • Defects in secondary aggregation
    • Deficiency of contents of one of the granules
    • Inheritance is variable (heterogeneous group)
    • Bleeding is usually mild to moderate but can
    be exacerbated by aspirin
    • Clinical: easy bruising, menorrhagia, and
    excessive postpartum or postoperative
    bleeding
    Storage Pool Disorders
    • Typical Laboratory Findings:

    – Usually normal platelet count


    – Morphology is variable
    – Platelet aggregation shows primary wave but
    absence of secondary wave when stimulated
    with ADP, epinephrine, arrachidonic acid
    – Platelet aggregation with thrombin is usually
    normal (overrides need for granule release)
    – Ristocetin agglutination is normal
    Storage Pool Disorders
    • Delta Storage Pool Deficiency
    – Decrease amount of secretable ADP, ATP, serotonin, calcium
    – Often associated with disorders affecting granules in other
    cells
    • Chediak-Higashi Syndrome
    • Hermansky-Pudlak Syndrome
    • Wiskott-Aldrich Syndrome
    – Platelets are small with decreased number of both
    alpha and dense granules
    Storage Pool Disorders
    • Hermansky-Pudlak • Wiskott-Aldrich Syndrome:
    Syndrome: platelet disorders of dense granules
    deficiency of non-metabolic characterized by recurrent
    ADP; patients with pyogenic infections,
    oculocutaneous albinism Eczema, and
    thrombocytopenia
    • Chediak-Higashi Syndrome:
    patient with ocular albinism
    and characteristic silver-gray
    hair with dense granule
    storage pool deficiency
    Storage Pool Disorders
    • Alpha Storage Pool Deficiency
    – Decrease amount of Platelet Factor 4, PDGF, β-
    thromboglobulin
    – Gray Platelet Syndrome: deficiency of the alpha granules
    leading to an agranular appearance of platelets on Wright’s

    • Alpha and Delta Storage Pool Deficiencies


    – both
    Gray Platelet Syndrome

    • Alpha granule deficiency


    • Clinical: mild bleeding

    • Laboratory Findings:
    – Thrombocytopenia: 60 - 100 x 103/L
    – Platelets are large and appear “gray” on Wright’s stained
    smear (hence the name)
    – Marked deficiency of alpha granules
    – Dense granules are normal
    – Platelet aggregation studies are fairly normal since 2o
    aggregation wave due primarily to dense granule release
    Secretion Disorders
    Inability to Release Dense Granule Contents
     No abnormalities in  Includes defects in the
    platelet granules and of arachidonic acid pathway
     Deficiency of cyclo-oxygenase
    normal amount thus deficient conversion of
     Release defects is arachidonic acid to tromboxane
    caused by deficiencies A2
    of enzymes and “second  Deficiency of thromboxane
    synthetase
    messengers”
     Often called “aspirin-like” defects
     Abnormalities may be in  Granules are normal by electron
    the platelet stimulus- microscopy
    response coupling  Bleeding with mild, just as with
     Involves the metabolic aspirin, supporting fact that there
    pathways leading from are other pathways to activate
    receptor occupation to platelets (e.g., thrombin) that do
    platelet aggregation and not require this pathway
    secretion
    ABNORMAL PLATELET-COAGULANT
    PROTEIN INTERACTION
    • von Willebrand Disease
    von Willebrand Disease
    • The most common Classifications:
    inherited abnormality •Type 1: quantitative decrease in
    vWF and mild bleeding. Most
    of platelet function common variant (80%)

    •Type 2: qualitative abnormality


    • Platelets that are in the structure of vWF
    normal exhibit
    abnormal adhesion •Type 3: absent levels of vWF
    because of the absence multimers and a severe bleeding
    diasthesis
    or dysfunction of vWF
    Acquired Qualitative Defects
     MYELOPROLIFERATIVE DISEASE
    o Polycythemia vera, Chronic Myeloid Leukemia, myeloid
    metaplasia
     PARAPROTEINEMIAS
    o Multiple myeloma, Waldenstrom’s macroglobulinemia:
    interaction of paraprotein with platelets and coagulation
    factors
     UREMIA
    o Uncleared metabolic product guanidinosuccinic acid acts as
    inhibitor of platelet function by inducing endothelial cell Nitric
    Acid release
     LIVER DISEASE
     Multifaceted defect in coagulation, high levels of circulating
    fibrin degradation products, reduced production of factor VII
     DRUG THERAPY
     Aspirin: powerful inhibitor of platelet thromboxane A2
    synthesis through deactivation of cyclo-oxygenase (irreversible
    effect)
     NSAIDS: like ibuprofen, indomethacin. Inhibit platelet function
    but is reversible

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