Primary Haemostasis and Platelet Disorders Flashcards
Steps of primary haemostasis
Platelet capture - mediated by vWf from endothelial cells and exposed in subendothelial matrix
Platelet Adhesion - more in high shear env. Collagen and integrin binding to creat firm adhesion.
Platelet activation - occurs following intracellular signalling cascade mediated by adherance. Causes membrane flipping, degranulation, Phospholipid metabolism and Surface fibrinogen receptor changes
Platelet aggregation - mediated by fibrinogen b/w platelets and there is ongoing fibrin and thrombin production by 2ry haemostasis
Promotes endothelial tight junction and clearance.
What is Scott Syndrome
GSD
Unable to undergo membrane flip to expose PS
What is Glanszmann Thrombopathia
Cat case study
Abnormal fibrinogen receptor resulting in defective platelet aggregation
What is Platelet delta storage disease
Am Cocker Spaniel
reduced platelet response to ADP results in reduced aggregation. Associated with post-op bleeding.
Clinical signs of Primary haemostatic disorder
Petechiae
Ecchymosis
Mucosal haemorrhage
Bleeding after venepuncture
BMBT - indications and reliability
For dogs with normal plt count and normal coags.
Evaluates primary haemostasis - platelet functional defects or vWD
Very operator dependent. <4min is a general estimate for normal
Must use standardised incision device for accuracy
Ideally performed without sedation
Low sensitivity reported. Not specific for cause of defect.
High interobserver variability
Causes of thrombocytopenia
Clumping - esp cats
ITP
Haemorrhage
Splenic sequestration
Cyclical haematopoesis of Grey Collies
CKCS macrothrombocytopenia
Myelosuppression
vWF Assay Test principles, interpretation and reliability
The amount of low,. medium and high MW vWF multimers is assessed in the patient sample by ELISA.
Reported as a vWF:Ag value out of 100% where the % refers to the %of a normal pooled sample. Some patients can have >100% as a result.
Reference intervals vary by lab. Typically >70% considered normal.
Type I disease - low multimer concentration but full spectrum of sizes
Type II lack of high MW vWF, resulting in variable %. Requires qualitative vWF assay for diagnosis.
Type III severe reduction/absence of all multimers
Not highly sensitive(can miss type II) but is specific, though can be affected by illness.
What is qualitative vWF assay
Measures vWF collagen binding activity. Dependent on high MW vWF
Necessary for diagnosis of type II vWD
Limited availability
Gold standard for platelet function testing
Platelet aggregometry
In vitro induction of platelets with various agonists (can change agonist to assess different mediators of aggregation)
Measures lag from introduction to aggregation as well as rate of aggreegation
Limited availability. Mostly experimental
Indications, reliability of PFA-100
Measures platelet adhesion under shear stress using ADP as an agonist
Closure time is reliant on vWF and normal platelet function. So is a global assessment of primary haemostasis.
Less reliable than aggregometry for detection of drug induced inhibition of platelet function
Use of flow cytometry in primary haemostatic disorders
Can be used to assess platelet activation, function and surface receptors
Used to diagnose Scott Syndrome and Glanszmann thrombocytopathy
Recent study used for detection of anti-platelet antibodies in ITP dogs - reported all primary ITP dogs were positive and 20% with non-ITP thrombocytopaenia were also positive.
Previous studies have not demonstrated APA in all ITP cases
Persistence of APA was not associated with response, but relapse was associated with return of APA.
JSAP 2018 - disease associations in feline thrombocytopaenia
Haematologic infectious disease and neoplasia were the most common causes
Primary ITP was less common than in dogs.
11% positive for FeLV
Only 7% had signs of haemorrhage at diagnosis
