Lab Evaluation of Hemostasis I Flashcards
What are the functions of hemostasis?
vascular integrity
platelet numbers and function
coagulation
What are the steps of hemostasis?
vasoconstriction
forming the platelet plug
fibrin formation - blood clotting
What is the vascular phase of hemostasis?
vascular injury
transient vasoconstriction
exposure of subendothelial matrix with platelet and aggregation
exposure of tissue factor and imitation of coagulation
What are the lifespan of platelets?
4-6 days
What is platelet senescence?
increased membrane phosphatidylserine (PS)
What are functions of platelets?
platelet plug formation
accelerate coagulation
vascular integrity
various roles in inflammation and tumor metastasis
How do platelets accelerate coagulation?
platelet procoagulant activity PF3
platelet factor 4
What aids in platelet adhesion?
von Willebrand factor
What are the factors involved in primary hemostasis?
TxA2 - product of arachidonic acid metabolism
PAF
ADP
What is the name of the platelet fibrinogen receptor?
GPIIb-IIIa
What binds fibrinogen?
active GPIIb-IIIa
Explain how platelets are activated
phosphatidyl serine on inner side of platelet membranes —> activated and now exposed —> platelet procoagulant activity
What are the roles of fibrinogen?
- protein that binds platelets together
- substrate when thrombin acts to form fibrin which forms meshwork to strengthen clot
Go watch this video
http://www.youtube.com/watch?v=0pnpoEy0eYE
What are hemostatic screening tests - 3 most important ones?
platelet count
MPV (mean platelet volume)
buccal bleeding time
What can platelet aggregates result in?
false thrombocytopenia - so look at blood films
Which species has a larger mean platelet volume? Lower?
higher: cats
lower: cattle
What leads to an increased mean platelet volume?
enhances thrombopoeisis in response to thrombocytopenia
some animals with myeloid neoplasms (because immature precursors get released [megakaryocyte])
hereditary macrothrombocytopenias in dogs
spuriously increased - platelet aggregates, storage of blood at 5 C
What are problems with mpv determinations?
inaccurate when platelet activation and aggregation is present (because when platelets are stimulated, they swell; also aggregate and form clots)
What is this?
buccal bleeding time
What is the use of a buccal bleeding test?
platelet function
What are platelet function assays?
clot retraction - allow a blood sample to clot and normal platelets with normal function over hours should retract and squeeze serum
What are anti platelet antibody assays?
test for immune-mediated thrombocytopenia
What causes macroplatelets?
enhanced thrombopoiesis
myeloid neoplasms
hereditary macrothrombocytopenias in dogs
What does this show?
immune-mediated thrombocytopenia
What morphological signs can indicate thrombocytopenia?
petechial and ecchymotic mucosal or cutaneous hemorrhages
epistaxis
When is there a hemorrhagic tendency regarding thrombocytopenia?
occurs when platelet counts are below 25,000
consider concurrent DIC
What is the pathogenesis of thrombocytopenia?
decreased platelet production
increased platelet utilization
increased platelet destruction
sequestration of platelets (spleen)
massive hemorrhage
inherited macrothrombocytopenias in dogs
What are some causes of decreased platelet production?
myelophthisis
myeloid neoplasms
aplastic anemia
chronic E. canis infection
megakaryocytic thrombocytopenia
inherited cyclic hematopoiesis
How does myelodysplastic syndrome cause decreased platelet production?
too many blast cells
megakaryocytes often become dysplastic (abnormal in shape or size) or fail to mature properly
If you see no mature megakaryocytes in a marrow aspirate, what is happening? What is the treatment?
possible precursor immune-mediated thrombocytopenia
prednisone
What are some causes of increased platelet utilization?
DIC and thrombosis
vasculitis, hemangiosarcoma in dogs, and other disorders resulting in vessel injury
platelet activating factor
What are causes of increased platelet destruction?
primary immune-mediated (autoimmune) thrombocytopenia, most common in dogs
infectious agents - tick-borne diseases including Babesia, Ehrlichia, Anaplasma, Cytauxzoon
What does sequestration of platelets cause?
splenomegaly
hypothermia
What is hypersplenism?
when splenomegaly results in the permanent removal of platelets
spleen has gone crazy phagocytosing normal cells
What does massive external hemorrhage cause?
platelet counts seldom decrease below 100,000/uL due to hemorrhage alone
secondary to anticoagulant rodenticide poisoning - low as 60,000 uL
What is hereditary macrothrombocytopenias in dogs?
big platelets
lower platelet counts
cavalier King Charles spaniels
Which breed is predisposed to macrothrombocytopenia?
cavalier King Charles spaniels
What are platelet function defect laboratory findings?
prolonged bleeding time
NORMAL platelet counts, usually
usually normal platelet morphology
normal coagulation tests
What are acquired platelet function defects?
antiplatelet antibodies (GPIIb/IIIa fibrinogen receptor)
FDPs antagonize fibrinogen binding
high serum immunoglobulin coats platelets
What can result in aquired platelet defects?
uremia and liver disease
drugs, especially non steroidal anti-inflammatory drugs such as aspirin and phenylbutazone
myeloid neoplasms with abnormal platelet production
What are intrinsic platelet function defects - hereditary platelet defect?
something is wrong with the platelet itself
adhesion defect
aggregation defect
What are extrinsic platelet function defects - hereditary platelet defect?
von Willebrand factor deficiency
fibrinogen deficiency
What is Bernard-Soulier Syndrome? What does it cause?
inherited platelet adhesion defect
macrothrombocytopenia (increased MPV)
mucosal bleeding disorders (epistaxis, hematuria, gingiva, vulva after mating)
defect in the GPIX (GP9) gene
What are some inherited platelet aggregation defects?
glanzmann’s thrombasthenia
dense granule deficiency
ADP receptor P2Y12 defect
signaling pathway defects in GPIIb/IIIa activation
What problems can you get with an adhesion or aggregation problem?
have lack of adhesion molecule 2,3ba and don’t get platelets bound to each other
or, signal that’s headed to activate factor (if signal problem) don’t get platelets bound to each other (lack of signal transduction)
lack of receptor
lack of ADP coming from other platelets
What happens when you don’t have ADP?
don’t have agonist produced for further degranulation
List the 4 defects leading to reduced platelet aggregation
have lack of adhesion molecule 2,3ba and don’t get platelets bound to each other
or, signal that’s headed to activate factor (if signal problem) don’t get platelets bound to each other (lack of signal transduction)
lack of receptor
lack of ADP coming from other platelets
What happens in a PF3 defect? Which breed(s)?
epistaxis, prolonged bleeding with cutaneous bruising after surgery, hyphen, intramuscular hematomas
German shepherds
In a PF3 defect, list what platelet function tests are normal - mucosal bleeding time, clot retraction, platelet aggregation and secretion, coagulation tests (PT, APTT, ACT)
normal
What is a PF3 defect a defect in?
translocation and exposure of phosphatidyleserine on the platelet surface, resulting in impaired coagulation in vivo
What happens with enhanced platelet functions? What are some diseases?
activated or hyperactive platelets
diabetes mellitus, nephrotic syndrome, EPO treatment, FIP virus, heartworm disease, allergic respiratory disease
What binds with vWF?
FVIII even though produced by different genes
What is von Willebrand Disease?
defect in platelet adhesion resulting in prolonged bleeding times
not necessarily a platelet problem, just factor that binds to that
What leads to thrombocytosis?
some chronic inflammatory conditions - increased TPO by inflammatory cyutokines
ongoing hemorrhage, especially if iron deficiency is present
If a dog has a splenectomy, what happens?
leads to increased platelets - inflammatory response to surgery and a fluid shift
