107 Platelet Disorders Flashcards
Thrombocytopathies most commonly are
Intrinsic thrombocytopathies are ___ common than extrinsic thrombocytopathies in small animals
von Willebrand’s disease is the most common ____thrombocytopathy and is seen in many breeds, whereas most of the other intrinsic platelet disorders are breed specific
inherited but also may be acquired.
more common
extrinsic
Tx:
DDAVP
plt concentrate
cryo or plasma
only vWD type I
intrinsic disorders
any vWD
Extrinsic platelet disorders are characterized by:
lack of a functional protein needed for platelet adhesion
vWD in dogs is caused by:
vWF is a:
MoA:
Platelets contain only a small amount of:
majority
deficiency or dysfunction of von Willebrand factor (vWF)
plasma protein of variably sized multimers
1. mediates platelet hemostatic function
2. as well as circulates with and stabilizes Factor VIII
small
richest source is in the endothelial cells
in plt vWD found in:
in EC vWF found in:
a-granules along with
weibel palade bodies
inheritance:
Type 1 autosomal dominant or recessive
type II and III autosomal recessive
no sex pred
3 types
Type I is a quantitative reduction in all multimers
-common
Type II vWD reductions large multimers (most important in hemostasis)
-rare
Type III vWD absolute lack of vWF
-rare
C/S Petechiae and ecchymoses are:
uncommon
I - variable
II and III bad
BMBT
time:
variables that alter results:
prolonged result is consistent with:
3 minutes
skin thickness, skin temperature, age, gender, hematocrit, intrinsic thrombocytopathia or von Willebrand’s disease
definitive diagnosis:
measurement of the vWF : antigen concentration
tx 3:
cryoprecipitate (1 unit/10 kg body weight IV within 8 hours of thaw)
1 unit equates to cryoprecipitate from 200 ml fresh frozen plasma
Desmopressin acetate (deamino 8-d-arginine vasopressin, DDAVP) -stimulate endothelial V2 receptors to release intracellular stores of vWF ONLY Type 1 vWD patients have some response to DDAVP. Types II and III have little to no response to DDAVP
Intrinsic platelet disorders are those:
inherent to platelet
Chediak-Higashi syndrome (CHS): inheritance: species/breed: MoA: tx:
auto. recessive disease
prolonged bleeding times w normal platelet #
humans and cats
-intrinsic platelet storage pool deficiency
-altered lysosomal granule formation and abnormal degranulation in neutrophils and platelets
-platelet dense granules lacking in this disease
= aggregation response to collagen is absent
platelet concentrates has been shown to correct abnormal oral mucosal bleeding times
Glanzmann's thrombasthenia: inheritance: species/breed: MoA: tx:
humans and dogs
Otterhounds and Great Pyrenees
deficiency in αIIbβ3 integrin
CS secondary to lack of fibrinogen binding to αIIbβ3
bone marrow transplantation and gene therapy
perioperative platelet-rich plasma
clot retraction assay can be used as a screening tool in:
how do you do it?:
patients w normal RBC and plt # retraction is impaired by: thrombocytopathia abnormalities in fibrinogen some coagulation defects
5 ml of whole blood into a sterile glass tube (without any anticoagulant)
- wooden applicator is inserted into the tube and blood
- tube then is sealed with plastic paraffin film before incubation at 37° C
- assessment of clot formation and clot retraction is noted over 8 to 24 hours
- within 2 to 4 hours a normal clot retracts markedly
- results are recorded as complete clot retraction (retraction occurred and serum was found surrounding the clot) or failed clot retraction (no serum was found surrounding the clot)
Greater Swiss Mountain Dog:
P2Y12 receptor
bled excessively after an ovariohysterectomy
lack of a functional P2Y12 receptor prevents activation via ADP-induced outside-in signaling for fibrinogen binding on the platelet surface at the αIIbβ3 integrin
important because of the growing use of clopidogrel as an antithrombotic agent. Clopidogrel blocks ADP from binding at the P2Y12 receptor, reducing platelet activation
Canine Scott syndrome (CSS)
MoA:
Dx:
Tx:
German Shepherd Dogs
autosomal recessive
inability for phosphatidylserine to be externalized for the creation of a procoagulant surface
-also have a decreased microparticle release
Dx: flow cytometry because typical coagulation testing and point-of-care analysis with the Platelet Function Analyzer-100 or thromboelastography did not show a difference between platelet function of affected and nonaffected dogs
Spontaneous hemorrhage CANNOT be prevented by treatment
however, perioperative cryopreserved platelet-rich plasma transfusions plus a postoperative antifibrinolytic agent has been used with success
Idiopathic asymptomatic macrothrombocytopenia in Cavalier King Charles Spaniels (CKCS)
inherited autosomal recessive platelet defect
mutation in β1-tubulin likely leads to altered proplatelet formation in megakaryocytes
Norfolk Terriers
CKCS have not been found to have any clinical bleeding or any abnormalities on platelet aggregation testing
Aquire plt dysfunction:
acquired vWD
hypothyroidism
hydroxyethyl starch and dextran solutions also have been implicated in acquired vWD
Drugs
aspirin, ticlopidine, clopidogrel, as well as some antibiotics and nonsteroidal antiinflammatory drugs
Uremic:
defects in platelet adhesion, secretion, and aggregation
- defects in vWF function (probably receptor binding) are thought to play a major role
- normal to increased vWF levels, but platelet function can be improved in the uremic patient by transfusion of cryoprecipitate or administration of DDAVP
- > nitric oxide and prostacyclin that can alter vascular tone and platelet function
- some of the uremic toxins are believed to act as direct platelet inhibitors by competing for receptor binding
