Platelet Qualitative Disorder Flashcards
an instrument designed to measure
platelet function in a suspension of Citrated WB or PRP.
Aggregometer
TYPES OF PLATELET AGGREGOMETRY STUDIES
- Optical platelet aggregometry
- Whole blood platelet aggregometry
- Platelet lumi aggregometry
Sample used in Optical platelet aggregometry
PRP
Testing principle of Optical platelet aggregometry
Light transmittance
Baseline 0% Transmission scales down to 100% transmittance.
Optical platelet aggregometry
4 PHASES of Optical platelet aggregometry
- Baseline
- Primary-wave aggregation
- ADP/ATP release
- Second-wave aggregation
Sample used in Whole blood platelet Aggregometry
Whole blood (WB)
Testing principle of Whole blood platelet Aggregometry
Electrical impedance
As platelet aggregate, platelets collects on
the electrodes impeding the current. The change is amplified and recorded.
Whole blood platelet Aggregometry
Sample used in Platelet lumi Aggregometry
Whole blood (WB) or PRP
Testing principle of Platelet lumi Aggregometry
Chemiluminescence
Principle: Luciferin-luciferase enzyme (Reagent) added is oxidized by ATP which generates proportional chemiluminescence
Platelet lumi Aggregometry
Particularly sensitive to ATP release
Platelet lumi Aggregometry
AGONIST USED IN AGGREGOMETRY with Biphasic curves
- Thrombin
- ADP
- Epinephrine
AGONIST USED IN AGGREGOMETRY with Monophasic curves
- Collagen
- Arachidonic Acid
- Ristocetin
Receptors of Thrombin
PAR-1,PAR-4;
GP Iba & GP VI
Relatively unaffected by membrane disorders or enzyme deficiencies.
Thrombin
Receptors for ADP
P2Y1 & P2Y12
Most commonly used agonists.
ADP
Receptor for EPINEPHRINE
A2- Adrenergic Receptor
Cannot induce aggregation in storage pool disorders
EPINEPHRINE
Receptors for COLLAGEN
GP Ia/IIa & GPVI
Loss of response may indicate membrane abnormality, secretion defect or antiplatelet
drugs
COLLAGEN
Receptors for ARACHIDONIC ACID
TPa & TPb
Assess platelet eicosanoid pathway
ARACHIDONIC ACID
Receptor for RISTOCETIN
GP Ib/IX/ V with vWf
For the diagnosis of BSS and vWf
RISTOCETIN
Disorders of Platelet Adhesion:
Bernard-Soulier Syndrome (Giant platelet syndrome)
Inherited as Autosomal Recessive disorder in which the GP Ib/1X/V complex is missing from the platelet surface or exhibits abnormal function.
Bernard-Soulier Syndrome (Giant platelet syndrome)
Inability to bind to VWF accounts for the inability of platelets to adhere to exposed sub endothelium and results to the bleeding characteristics of this disorder.
Bernard-Soulier Syndrome (Giant platelet syndrome)
Laboratory features : Giant platelets
Bernard-Soulier Syndrome (Giant platelet syndrome)
PLATELET AGGREGATION in
PLASMA OR PLATELET GRANULES
- Ionized Calcium
- Fibrinogen
PLATELET AGGREGATION in
PLATELETS
- GP IIb/IIIa
- ATP/ADP
Disorders of Platelet Aggregation:
Glanzmann Thrombasthenia
Deficiency or abnormality of the platelet
membrane glycoprotein GPIlb/Illa complex.
Glanzmann Thrombasthenia
Laboratory features : Platelet aggregometry.
Macrothrombocytopenia and prolonged bleeding time.
Bernard-Soulier Syndrome (Giant platelet syndrome)
Normal platelet count and morphology.
Abnormal aggregation. Prolonged bleeding time.
Glanzmann Thrombasthenia
Clinical Manifestations: Bleeding of all types
Glanzmann Thrombasthenia
Dense Granule Deficiency:
- Hermansky-Pudlak syndrome
- Chediak- Higashi syndrome
- Wiskott-ALdrich syndrome
- Thrombocytopenia-absent
- radius (TAR) syndrome
Alpha Granule Deficiency:
- Gray Platelet Syndrome
Manifestations:
- Tyrosinase positive oculocutaneous albinism
- Lysosomal dysfunctions
- Ceroid-like depositions in the RES
- Profound platelet dense granule deficiency.
- Severe bleeding is RARE.
Hermansky- Pudlak Syndrome
Hallmark: Swiss-cheese platelets. This abnormality consists of marked dilation and tortuosity of the surface-connecting tubular system
Hermansky- Pudlak Syndrome
Manifestations:
- Partial oculocutaneous albinism
- Frequent pyogenic bacterial infections (severe immunology defects).
- Giant lysosomal granules
- Platelet dense granule deficiency (which leads to hemorrhage ).
- Lymphocytic proliferation in the liver, spleen and marrow.
- Macrophage accumulation in tissues.
- Severe pancytopenia
- Usually results to death in early age.
Chediak-Higashi Syndrome
- X-linked disease
- Affects primarily males.
- Mutations in the WAS gene on the short arm of the X chromosome. (Xp11.23)
Wiskott-Aldrich syndrome
The WASp gene plays a crucial role in
actin cytoskeleton remodeling
Classic form of WAS:
Eczema-thrombocytopenia immunodeficiency syndrome
- Immune dysfunction (susceptibility to bacterial, viral and fungal infections).
- Microthrombocytopenia
- Severe Eczema.
- Bleeding episodes (mod-severe).
Eczema-thrombocytopenia immunodeficiency syndrome
- Decreased platelet dense granules.
- Platelets are small- Microthrombocytes.
Other instances where small platelets are hallmark features: TORCH Infections. ( bacterial infection that transmitted vertically from mother to the baby)
Wiskott-Aldrich syndrome
- Rare autosomal recessive disorder
- Congenital absence of radial bones
- Cardiac and skeletal abnormalities
- Thrombocytopenia
- Structural defects of platelet dense granules.
Thrombocytopenia with absent radii syndrome (TAR)
mutation in the NBEAL2 gene (614169) on
chromosome 3p21.
Gray Platelet Syndrome
Characterized by the specific absence of
morphologically recognizable alpha granules.
Gray Platelet Syndrome
- Lifelong mild bleeding tendencies.
- Moderate thrombocytopenia
- Fibrosis of the marrow
- Large platelets with gray appearance on a wright-stained smear.
Gray Platelet Syndrome
Membranes & precursors of gray platelet syndrome have
P-selectin and GPIIB/IlIA expressions
a rare disorder in which both alpha and dense granules are deficient. Inherited in an autosomal dominant manner.
Alpha-Dense storage pool deficiency
autosomal dominant bleeding disorder, this results to a deficiency in multimerin. Many alpha granules are degraded by proteases.
Quebec Platelet disorder
DRUGS INFLUENCING PLATELET FUNCTIONS
- Aspirin
- Clopidogrel
- Tirofiban
- Atopaxar
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
a thienopyridine derivative, binds specifically and irreversibly to the platelet P2RY12 purinergic receptor, inhibiting ADP-mediated platelet activation and aggregation.
CLOPIDOGREL
a reversible, competitive inhibitor of GP Ilb/Illa receptors, exerting its effects via the prevention of the binding of fibrinogen and other ligands, resulting in the inhibition of platelet aggregation.
TIROFIBAN
is a potent protease-activated receptor (PAR-1) antagonist targeting the G-coupled receptor and modulating thrombin-platelet-endothelial interactions.
Atopaxar (E5555)
