Lecture 7: coagulation I: platelets and primary hemostatics Flashcards
Hemostasis is requires intricate balance between __ and __
coagulation and Fibrinolysis
define coagulation
generates thrombin—> converts fibrinogen to fibrin—> clot formation
define Fibrinolysis
degradation of fibrin via plasmin
what are some causes of hypocoagulation
end stage DIC, liver failure (not producing coagulation factors)
what are some causes of hypercoagulation
- Severe anemias (IMHA)
- Sepsis
- Protein losing nephropathy
- Endocrine- Cushing, DM
describe normal conditions in blood vessels
anticoagulable and profibrinolytic
what are the 4 steps in hemostasis
- Vasoconstriction
- Primary hemostasis- platelets and endothelium
- Secondary hemostasis- coagulation cascade
- Fibrinolysis/ anti-thrombotic events
what are black arrows pointing at
platelets
describe appearance of platelets
anucleate with blue cytoplasm a and reddish cytoplasmic granules
what is the equivalent to platelets in non-mammalian species
thrombocytes
What indicated by circles
black: thrombocytes
red: lymphocytes
what is platelet structure
phospholipid bilayer membrane
Glycoproteins for activation, adhesion and aggregation
platelets Are produced by __ within the __
megakaryocytes within the bone marrow
what this and what happening
megakaryocyte with budding off bit to form platelet
what is platelet circulating lifespan
5-9 days
platelet production is regulated by __
thrombopoietin
thrombopoietin is produced by __
hepatocytes
thrombopoietin production enhanced by inflammatory cytokine __
IL-6
what is platelet function
Adhesion, activation, aggregation and granule secretion to promote hemostasis
Vascular injury stimulates ___expression on subendothelial cells to initiate coagulation
tissue factor
what are the steps of primary hemostasis
- Platelet adhesion
- Platelet shape change
- Platelet secretion of granules
- Platelet aggregation
What contents are released in platelet granules that promote platelet activation and development
- ADP
- Serotonin
- Fibrinogen
- Factor V
- Factor XI
what seen here and what lab work finding would it cause
platelet clumping—> pseudo thrombocytopenia
define thrombocytopenia
decreased platelet concentration
define thrombocytosis
increased platelet concentration
what these
platelet clumps
how do you estimate platelet concentration
- Count number of platelets in ten 100x fields within mono layer
- Calculate average
- Multiply average by 15,000 (dogs) or 20,000 (cats)
what are the 3 causes of defects in primary hemostasis
- Thrombocytopenia
- Thrombopathy
- Deficiency in VWF
what causes thrombopathy
- defect in glycoprotein (GPIb or GPIIa/IIIb)
- Abnormal granule function/ release
what are some clinical signs of defects in primary hemostasis (thrombocytopenia, thrombopathy, deficient VWF)
- Petechiae and/or ecchymoses
- Gingival bleeding
- Hematuria
- Melena
- Epistaxis
what wrong and what some ddx
Petechiae, epistaxis
Ddx: thrombocytopenia, thrombopathy, deficient WVF
what are the 4 main causes of true thrombocytopenia
- Splenic sequestration
- Decreased production by bone marrow
- Increased consumption
- Increased destruction
what are some causes of splenic sequestration leading to thrombocytopenia
- Marked splenic congestion
- Heat stroke
3, neoplasia
with suspected decreased production of platelets must evaluate __ and find __ to confirm
bone marrow, megakaryocytic hypoplasia
with bone marrow panhypoplasia typically see __ before __
leukopenia before thrombocytopenia
what are some causes of bone marrow pan hypoplasia
- Drugs- chemo, estrogen
- Toxins
- Radiation
dog presents with mucosal petechiae, suspect thrombocytopenia. Do bone marrow biopsy and see following- what wrong/ cause
bone marrow panhyoplasia
Cause: decreased production
what are some causes of decrease production of platelets leading to thrombocytopenia
- Myelopthisis: inflammation, neoplasia, myelofibrosis
- Infectious agents: erhlichiosis, FeLV/FIV, EIA, BVD
what can cause increase platelet utilization/consumption leading to thrombocytopenia
trauma, hemorrhage, neoplasia, DIC
what is the major cause of thrombocytopenia caused by platelet destruction
immune mediated thrombocytopenia
what is primary causes of immune mediated thrombocytopenia
antibodies against platelet antigens
what are some secondary causes to Immune mediated thrombocytopenia
lupus, neoplasia, drugs, vaccines (distemper, parvo, panleukopenia)
what breeds are predisposed to macrothrombocytopenia
KCCS and akitas
what is cause of macrothrombocytopenia
mutation in B1 tubulin gene—> alternates megakaryocyte proplatelet formation and release
t or f: dogs with macrothrombocytopenia have no clinical signs or bleeding tendencies
true
t or f: total platelet mass (plateletcrit) is normal in dogs with macrothrombocytopenia
true
what abnormality is seen on bloodwork in dogs with macrothrombocytopenia
giant platelets (high MPV) with low platelet count
from KCCS- what arrow pointing at
macrothrombocytopenia
what is platelet count on CBC for thrombocytopathy and deficiency in VWF
normal platelet count on CBC, abnormal function
VWF is produced by __ and __
megakaryocytes and endothelial cells
VWF is necessary for normal ___
platelet adhesion to collagen
What is the most common inherited bleeding disorder in dogs
VWF disease
what breed is VWF disease most common in
Doberman pinscher
what is cause of type 1 VWF disease
plasma concentrations of all size VWF multimers are <50%
what is cause of glanzmann thrombasthenia
deficiency of GPIIb-IIIa: platelets unable to bind fibrinogen—> impaired aggregation and clot formation
what are some tests for primary hemostasis disorders
- CBC- assess platelets
- Buccal mucosal bleeding time (BMBT)
- Clot retraction time
- Platelet function analysis
what patients is BMBT contraindicated in and why
thromboccytopenic patients- doesn’t add any additional information (will be prolonged if thrombocytopenic)
when in BMBT indicated
normal platelet count with concurrent clinical signs of primary hemostasis disorder
what is BMBT results
normal result 2-4 minutes
>4 minutes- prolonged
what are your ddx for prolonged BMBT
thrombocytopenia, VWD, thrombopathy
how do you test for VWD
ELISA- vWF antigen measured by quantitative ELISA with species specific antibodies to vWF
platelet function analyzer results are reported as __ in seconds
closure time
prolonged closure time from platelet function analyzers indicates what disorders
thrombocytopenia
VWD
Inherited thrombocytopathies
what are some causes for thrombocytosis
- Physiologic
- Reactive/inflammatory
- Recovery from thrombocytopenia
- Iron deficiency
- Paraneoplastic
- Post splenectomy
- Essential thrombocythemia
- Megakaryocytic leukemia
what is cause of physiologic thrombocytosis
epinephrine induced splenic contraction—> increased number of circulating platelets (mild)
Due to excitement/fright
what is cause of reactive/inflammatory thrombocytosis
inflammation—> IL-6 stimulates TPO release—> increase platelet production
what causes paraneoplastic thrombocytosis
neoplasm producing IL-6–> stimulates TPO release—> increase platelet function
What must you evaluate to dx essential thrombocythemia and megakaryocytic leukemia
bone marrow
