4: Aualitative Disorders Flashcards by Gay Amor Tipolo Gacang

Plasma count in Platelet Rich Plasma

200-300 x 10^9/L

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Sample used in Optical Platelet Aggregometry

PRP

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Principle used in Optical Platelet Aggregometry

Light transmittance aggregometry

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Baseline 0% transmission scaled down to 100% transmittance

Optical Platelet Aggregometry

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5 phases of Optical Platelet Aggregometry

Baseline
Shape change
Primary-wave aggregation
ADP/ATP release
Second-wave aggregation

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Anticoagulant used in Whole Blood Aggregometry

Citrate

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Sample used in Whole Blood Aggregometry

Whole blood

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Principle used in Whole Blood Aggregometry

Electrical impedance

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As platelet aggregate, platelets collect on the electrodes impeding the current. The change is amplified and recorded.

Whole Blood Aggregometry

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Sample used in Platelet Lumi Aggregometry

WB and PRP

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Principle used in Platelet Lumi Aggregometry

Chemiluminescence

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What reagent is added in Platelet Lumi Aggregometry test that is oxidized by ATP which generates proportional chemiluminescence

Luciferin-luciferase enzyme

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Typically the first agonist used in Platelet Lumi Aggregometry because it induces full secretion

Thrombin

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Biphasic agonists

Thrombin
ADP
Epinephrine

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Monophasic agonists

Collagen
Arachidonic acid
Ristocetin

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What curve is related to the secretion of the granules

Biphasic curve

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What curve only produces primary wave and is used to assess platelet aggregation

Monophasic curve

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Receptors of thrombin

PAR1 & PAR4
GPIba & GPVI

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Receptors of ADP

P2Y1 & P2Y12

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Receptors of Epinephrine

A2-adrenergic

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Agonist that is relatively unaffected by membrane disorders or enzyme deficiencies

Thrombin

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Most commonly used agonist

ADP

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Cannot induce aggregation in storage pool disorder or eicosanoid synthesis pathway defects no matter how high its concentration

Epinephrine

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Does not work in WB aggregometry test for abnormalities of membrane binding sites and the eicosanoid synthesis pathway

Epinephrine

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Receptors of Collagen

GPIa/GPIIa & GPVI

Receptos of Arachidonic acid

TPa and TPb

Receptors of Ristocetin

GPIb/IX/V with vWF

Loss of response of this agonist may indicate membrane abnormality, secretion defect or antiplatelet drugs

Collagen

Agonist that assess platelet eicosanoid synthesis pathway

Arachidonic acid

Agonist used for the diagnosis of BSS and vWD

Ristocetin

A disease that cannot be corrected by additional of normal plasma or cryo

Bernard-Soulier Syndrome (Giant platelet syndrome)

The most frequent forms of BSS involves defects in ______ synthesis or expression

GPIba

Variants of BSS:

1. Normal but impaired functionality 2. Mutation that cause poor binding 3. Antibody to GPIb/V that case pseudo-BSS

Laboratory feature of BSS:

- Giant platelets - Macrothrombocytopenia (plts are large and fewer) - Prolonged bleeding time

Treatment of choice of BSS

Platelet transfusion note: must be leukoreduced to reduce alloimmunization

What therapy should be avoided in BSS

Antiplatelet therapy

Therapy in BSS that is useful for mucosal bleeding

Antifibrinolytic therapy

Dominant type of BSS

BOLZANO TYPE

In Glanzmann Thrombasthenia, GPIIb/IIIa complex is responsible for binding

fibrinogen vWF fibronectin and other adhesive ligands

0.5% of normal GPIIb/IIIa

Type 1 Glanzmann Thrombasthenia

10-20% of normal GPIIb/IIIa

Type 2 Glanzmann Thrombastenia

More severe type of Glanzmann Thrombastenia, with platelets lacking GPIIb/IIIa as well as intra platelet fibrinogen

Type 1

Highly recommend treatment for Glanzmann Thrombasthenia

Platelet transfusion

What should be avoided in the treatment of Glanzmann Thrombasthenia

Anticoagulant and antiplatelet agents

Treatment for Menorrhagia in Glanzmann thrombastenia

Hormonal therapy (Norethindrone acetate)

Clot retraction of Glanzmann and BSS

Glanzmann: Abnormal BSS: Normal

Platelet glycoprotein defect of Glanzmann Thrombastenia

GPIIb/IIIa

Platelet glycoprotein defect of BSS

GPIb/IX/V

Chromosome 19 mutation

Hermansky-Pudlak Syndrome

Manifestations: 1. Tryosinase positive oculocutaneous albinism 2. Lysosomal dysfunction 3. Ceriod-like depositions in the RES 4. Profound platelet dense granule deficiency

Hermansky-Pudlak Syndrome

For extensive surgery and prolonged bleeding of Hermansky-Pudlak syndrome, administer

Packed red cells and platelets

Hallmark of Hermansky-Pudlak Syndrome

Swiss-cheese platelets

This abnormality consists of marked dilation and tortuosity of the surface-connecting tubular system

Swiss-cheese platelets

Mutations in Chromosome 1

Chediak-Higashi Syndrome

What gene is responsible for Chediak-Higashi Syndrome

CHY-LYST-1

Manifestations: 1. Partial oculocutaneous albinism 2. Frequent pyogenic bacterial infections 3. Giant lysosomal granules 4. Platelet dense granule deficiency

Chediak-Higashi Syndrome

Has severe pancytopenia

Chediak-Higashi Syndrome

Macrophage accumulation in tissues

Chediak-Higashi Syndrome

Usually results to death in early age

Chediak-Higashi Syndrome

Mutations in the WAS gene on the short arm of the X chromosome (Xp11.23)

Wiskott-Aldrich Syndrome

Classic form of WAS

Eczema-thrombocytopenia Immunodeficiency Syndrome

Manifestations of Eczema-thrombocytopenia Immunodeficiency Syndrome

- Immune dysfunction - Microthrombocytopenia - Severe Eczema - Bleeding episodes

Hallmark of Wiskott-Aldrich Syndrome

TORCH infections

The platelets are small - Microthrombocytes

Wiskott-Aldrich Syndrome

Congenital absence of radial bones

Thrombocytopenia with Absent Radius Syndrome (TAR)

How many alpha granules are present in platelets

50-80

Characterized by large platelets

Gray Platelet Syndrome

Mutations in the NBEAL2 gene (614169) on chromosome 3p21

Gray Platelet Syndrome

Autosomal dominant bleeding disorder which results to a deficiency in multimerin

Quebec Platelet Disorder

Inhibits platelet aggregation and secretion in response to ADP, Epinephrine, and collagen

Aspirin

Inhibits prostaglandin synthesis by irreversible acetylation and inactivation of cyclooxygenase (COX-1) thereby inhibiting endoperoxide and thromboxane A2 which are necessary for platelet secretion

Aspirin

Binds specifically and irreversibly to the platelet P2Y12 purigenic receptor inhibiting ADP-mediated platelet activation and aggregation

Clopidogrel

Is reversible, competitive inhibitor of GP IIb/IIIa receptors, exerting its effects via the prevention of the binding of fibrinogen and other ligands, resulting in the inhibition of platelet aggregation

Tirofiban

A potent protease-activated receptor (PAR-1) antagonist targeting G-coupled receptor and modulating thrombin-platelet endothelial-interactions

Atopaxar (E5555) - Benzimidazole receptor (PAR1)