Platelet disorder Flashcards
What features are affected in plt disorders
- number ( [plt] )
- morphology (size, appearance)
- function
guideline procedure for Ix of inherited plt disorders
- FBC
- Abnormal # or size => Blood film
- Bleeding time not recommended
- PFA-100 as optional screening test but is not dx or Sn to mild plt disorders
- PFA-100: for screening use both CADP (collagen + ADP) and CEPI (collagen + epiniphrine)
What’s the gold Std for plt function
Light transmission aggregometry (LTA) - although poorly stadardised (variations in each lab)
Describe Light transmission aggregometry (LTA)
- measure change in optical density (/ light transmitance) over time after addition of agonist & stirred
- agonist (ADP, Epineph, Coll, risto) causes plt to change shape
-> plt aggregate w/ fibrinogen = inc light transmi.
*risto will change plasma VWF -> binds to GPIb-IX-V
Pathophysiology of Bernanard-Soulier syndrome
- thrombocytopenia, giant plt
- quant&qualt abnormalities in plt GPIb-IX-V cmomplex -> clump but not stick to damaged BV wall bc VWF-dependent adhesion affected
Expected results for PFA-100, LTA & flow cytometry for Bernanard-Soulier syndrome
- PFA-100 both CADP & CEPI: prolonged closure time
- LTA: absent ristocetin-induced plt agglutination (not agglut. w/ Hi risto)
- & not corrected even if adding normal plasma
- Confirms dx w/ Plt flow cyto w/ anti-CD42 - measure GPIb-IX-V
Pathophysiology of Glanzmann thrombasthenia (GT)
- quant/qual. defect GPIIb/IIIa that impairs plt aggregation
- quant of normal GPIIb/IIIa: T1 (0-5%), T2 (10-20%), T3 (50-100%)
- mutations in ITGA2B or ITGB3
Expected results for PFA-100, LTA & flow cytometry for Glanzmann thrombasthenia
- PFA-100 both CADP & CEPI: prolonged closure time
- LTA: absent in all agonist-induced plt aagregation except [Hi risto] (i.e. everything except hi [risto] is a flat line)
- confirm dx w/ Flow cyto w/ Aby CD41 (GPIIb) & CD61 (GPIIIa)
a) Pathophysiology of Hermansky-Pudlack syndrome (HPS)
b) Test to confirm
a) melanin granules & plt delta-granule deficient
b) LTA: sub-normal aggregatino in resp. to collagen
- EM: lack of delta granules
- defects in 9 genes = distinct HPS subtypes in man
Pathophysiology of Chediak-Higashi syndrome (CHS)
- melanin granules & plt delta-granule deficient bc abnormal packaging of granules (see irreg. granules in neutrophils)
=> quant/qualt abnormality in delta-granule => abnormal plt function
Tests to confirm Chediak-Higashi syndrome (CHS)
• LTA: sub-normal aggregation in response to collagen
• EM: lack delta-granules
• Dec: plt content of serotonin & ADP
Chediak-Higashi syndrome (CHS) expect to see in PB
• Peroxidase pos granules in neutrophils
• Irreg. granules in neutrophil
• neutropenia
a) Pathophysiology of Gray plt Syndrome (GPS)
b) lab Ix to confirm
a)lrg plts lack a-granules & their content
• NBEAL2
b) transmission EM: absence of a-granules
• Romanowsky stain: plts look grey (not light purple) bc lack granules
a) Pathophysiology of May-Hegglin anomaly
b) lab Ix to confirm
a) macrothrombocytopenia
• abnormal plt skeleton
• MYH9 (autos. dominance)
b) PB: Giant plt, thrombocytopenia & neutrophil inclusions (like dohle bodies)
• Immunofluorescence in WBC
pathophysiology of Wiskott-Aldrich syndrome (WAS)
• abnormal plt skeleton
• Thrombocytopenia, Sml plts
• X-linked recessive
• Plts aggregate poorly & have low # granules
