Platelet defects Flashcards
How does the PFA100 work?
· Citrated whole blood is aspirated at high shear rates through disposable cartridges containing an aperture within a membrane coated with either Collagen and Epinephrine (CEPI) or Collagen and ADP (CADP).
·These agonists together with the high shear stress, induce platelet adhesion, activation and aggregation leading to rapid occlusion of the aperture and cessation of blood flow termed the closure time (CT).
What cartridge does the PFA200 have that can detect the presence of clopidogrel more reliably than the PF100?
· The membrane of INNOVANCE® PFA P2Y is coated with ADP, PGE1 [Prostaglandin E] and Calcium chloride.
What is Wiskott-Aldrich syndrome and X- linked thrombocytopenia
- WAS= Rare X-linked disorder characterised by defects in the WAS gene
- Characterised by eczema, susceptibilities to infection and thrombocytopenia
- Bleeding can be severe
- Thrombocytopenia and small plts on blood film
- XLT: Related to WLS above but have an isolated bleeding tendency
What is Congenital amegakaryocytic thrombocytopenia?
- Inherited plt disorder caused by abnormalities in the expression or function of the thrombopoietin receptor c-mpl
- Usually starts as an isolated platelet disorder but progresses to eventually cause a severe aplastic anaemia
- Thrombocytopenia. Normal plt size on blood film
- Markedly reduced or absent megakaryocytes in the bone marrow
What are the MYH9 related diseases?
- Inherited plt disorders caused by abnormalities in the MYH9 gene (encodes for the heavy chain of myosin IIA)
- Most common= May- Hegglen syndrome
- Macrothrombocytopenia and neutrophilic Dohele body like inclusions on blood film
- Often have additional symptoms like hearing loss, glomerulonephritis and cataracts.
What is grey platelet syndrome?
- Rare AR trait characterised by a selective deficiency in the number and content of the alpha granules.
- Severe bleeding may occur
- Associated with myelofibrosis and splenomegaly
- Macrothrombocytopenia on blood film. Plts lack granules and appear grey.
- Diagnosis confirmed with electron microscopy
What is Bernard Soulier Syndrome?
- Caused by inherited abnormalities in the GP1b receptor.
- Mild or moderate macrothrombocytopenia but bleeding may be severe and fatal haemorrhages can occur
- Prolonged closure times with ADP and epinephrine with PFA-100
- Absent response to ristocetin on platelet aggregometry (normal response to all other agonists)
- Flow cytometry showing reduced/ absent GP1b
What are the disorders of platelet signalling?
- Group of heterogeneous abnormalities in platelet secretion and signal transduction.
- Can arise from abnormal function of platelet membrane receptors or their associated signalling pathways.
- Variable defects seen on the PFA100 and platelet aggregation tests.
- Usually a defect in platelet aggregation to one or more agonist which is often accompanied by an absence of secondary aggregation in response to some or all agonists.
What is Glanzmanns thrombasthaenia?
- Normal platelet count
- Usually moderate to severe bleeding phenotype with fatal bleeds reported.
- Prolonged closure times with ADP and epinephrine with PFA-100
- Absence of platelet aggregation with all agonists except ristocetin.
- Flow cytometry showing reduced/ absent GPIIb/ IIA
What conditions are associated with a macrothrombocytopenia?
- MYH9 related disorders including May Hegglen syndrome
- Bernard Soulier
- Type 2B vWD
- Grey platelet syndrome
- Mediterranean macrothrombocytopenia
- X linked thrombocytopenia with dyserythropoiesis
What are the 4Ts in the hit score and what parameters give the highest score?
- Thrombocytopenia (>50% decrease but >20)
- Timing of onset (5-10 days, <1 day if recent exposure)
- Thrombosis (new) or anaphylactoid reaction
- Other causes for thrombocytopenia (none)
Why are both screening and confirmatory tests needed in the diagnosis of HIT?
o Immunoassays for heparin/PF4 are sensitive but lack specificity: only heparin antibodies which are platelet activating can cause the clinical syndrome of HIT.
o Functional assays are less sensitive but more specific.
Because of this, often two tests are performed: a screening test (to detect presence of antibodies) followed by a functional test (to ensure the antibodies cause platelet activation).
How are ADAMTS13 levels measured?
All assays based on the degradation of purified plasma derived, recombinant or synthetic VWF multimers by patient plasma ADAMTS13 followed by direct or indirect detection of vWF cleavage products.
What are some of the issues with ADAMTS13 assays?
- Measure ADAMTS13 activity in static conditions, fail to reflect the in vivo physiological blood flow conditions necessary for optimal protease activity.
- Added denaturing agents are required to promote the susceptibility of vWF multimers to cleavage by ADAMTS13 in the absence of shear.
- The use of shorter peptides as FRETS instead of full length vWF in some enzyme immunoassays may fail to detect a few inherited ADAMTS13 deficiencies since they measure metalloprotease activity independently of the exosite interactions with other vWF domains.
What is atypical HUS?
Thrombotic microangiopathy characterised by severe renal failure accompanied with dysregulation of the alternative complement pathway.
- Excessive activation of C3 convertase. Its partial consumption and production of C3a and C3b, which are deposited on the endothelial cell surface, leads to cell damage and destruction.
