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Path 3rd exam
Hemostasis to ?
69
Pathology
Professional
10/12/2011

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Term
What are bone marrow samples used for?
Definition
-diagnose and monitor disease
-need good aspirate, smear prep, staining, slide eval, and correlation w/ lab data
-aspirates are more common than biopsies
Term
Things that make you do a bone marrow aspirate
Definition
-hematologic abnormalities (cytopenia, morphology, cell pop)
-investigate history findings (fever, diag neoplasia)
-cause of lytic/prolif bone lesion
-explain chem findings
-diag infection
Term
fine needle aspirate
Pros and Cons
Definition
pro: evaluate cell morphology, no special fixation req, faster turn around.
con: may not reflect true cellularity, # of megakaryocyte, or focal processes, hemodilution
Term
Core Biopsy
Pros and Cons
Definition
pro: more acc in determining true cellularity, better at discerning conditions
con: slower turn around, hard to ID and eval cells
Term
If an animal is dead, what's the time limit to get a sample for a bone marrow aspirate?
Definition
<20 min.
Term
instruments to aspirate bone marrow
Definition
-15-18ga 1-2 in bone marrow asp needle
-10-12 mL syringe
-2-3% EDTA/saline sterile soln...if waiting >30 min to put on slide
Term
Sites to collect bone marrow:
-Dog/Cat
-Equine/Bovine
Definition
-iliac crest, trochanter fossa, prox humerus, sternebrae (careful close to lungs), costochondral jxn
-sternebrae, rib
Term
Don't send cytology in the same container as _____. why?
Definition
formalin b/c the fumes disrupt staining
Term
Always do ____ with a bone marrow aspirate.
Definition
CBC
Term
Hemostasis
Definition
the arrest of bleeding (hemorrhage) and maintenance of flow
Term
Three components that contribute to Hemostasis
Definition
Blood vessel wall, Plateles, Coagulation factors
Term
What's in the blood vessel wall?
Definition
endothelial cells, subendothelial collagen, subendothelial smooth muscle. All must be present in adequate quantities to be normal.
Term
*****Common Clinical Associations with Bleeding Disorders*****
Definition
Thrombocytopenia, Vit K antagonist, disseminated intravascular coagulation (DIC), liver failure, Vit K def due to bile duct obstruction
Term
Causes of thrombocytopenia
Definition
destruction, consumption, decreased production
Term
Anticoagulants
Definition
control coagulation. physical barrier, "non-wettable" surface (thromboresistant)
Term
Fibrinolysis
Definition
breaks down clot so it can be recanulated
Term
procoagulant
Definition
contraction of damaged vessel, exp of collagen fibers-decrease blood flow, decrease shear stress, production of vonwillebrand factor.
Term
Events following injury of blood vessels and subsequent hemorrhage:
Definition
Blood vessel contraction-reduce blood flow to injured areas.
Platelet adhesion to injured site: Primary Hemostasis (platelet plug)
Activation of coagulation system: Secondary Hemostasis (formation of fibrin)
Term
Primary Hemostasis
Definition
Platelets (formed in bone marrow, cytoplasmic fragments of megakaryocytes)
Platelet prod stimulated by thrombopoietin
Larger platelets are caled megaplaelets/giant platelets--sign of increased usage or destruction of platelets.
Term
3 Steps of platelet plug formation
Definition
Adhesion, release reaction, aggregation
Term
Adhesion of platelet, step 1 of Platelet plug formation
Definition
-blood vessel injury results in exposure of subendothelial structures to circulating blood
-subendothelial structures include collagen and smooth muscle
-von Willebrand factor acts as bridge btwn platlets and subendothelial collagen resulting in adhesion of platelets to collagen
Term
Granule release reaction, step 2 of platelet plug
Definition
-platelets adhere to subendothelial collagen--release their granular contents
-contents promote clotting: Calcium (cofactor in coagulation system), vonWillebrand factor (platelet adhesion to subendothelial collagen), ADP (induces expression of platelet surface receptors that bind to fibrinogen), Fibrinogen (causes platelets to adhere to each other)
Term
Platelet aggregation, step 3 of platelet plug
Definition
because of granule contents-platelets adhere to each other.
Term
Secondary Hemostasis
Definition
-if defect is small and blood flow is slow=platelet plug is enough
-defect is large, blood is swift--need stabilization of plug w/ fibrin. Formation of fibrin is from coagulation system.
-Intrinsic and extrinsic pathways of coagulation
Term
Factor III (tissue thromboplastin)
Definition
endothelial transmembrane protein w/ assoc cell membrane phospholipids
Term
Common Pathway
Definition
X->X+Ca,PF-3 convert Prothrombin (II) --> Thrombin (IIa) which will convert Fibrinogen -> fibrin, then Fibrin + XIIIa form the stable fibrin clot
Term
Intrinsic Pathway contains which factors
Definition
XII, XI, IX, VIII
Term
Extrinsic Pathway contains which factors
Definition
VII
Term
Common Pathway contains which factors
Definition
X, V, II, I
Term
Tissue Thromboplastin
Definition
Factor III, doesn't circulate, it's attached to fibroblasts and smooth muscle cells (and some endothelial cells)--promotes activity of extrinsic system by activating Factor VII
Term
Factor IV
Definition
is calcium and not listed in the pathway systems.
Term
Factors synthesized in the Liver
Definition
I, II, V, VII, VIII, IX, X, XI, XII, XIII
Term
Factors synthesized in macrophages
Definition
II, V, VII, X
Term
Vitamin K dependent factors--co-factor in carboxylation of the precursors of these factors
Definition
II, VII, IX, X
Term
All circulating factors, except V and VIII, are ____
Definition
proteases that activate the factor following them in the cascade
Term
Factor ___ & ____ are accelerators that promote more rapid activation of factors ___ and ___, respectively.
Definition
- V and VIII
-II and X
Term
Production of fibrin
Definition
-soft and gel-like and lacks strength
-strengthened with cross-links of individual fibrin molecules which is promoted by Factor XIII (fibrin stabilizing factor)
Term
Production of Factor II (thrombin) starting with Tissue factor bearing cell
Definition
TF w/ VIIa converts IX to IXa--diffuses to platelet surface and reacts with platelet activation/aggregation on the platelet.

TF w/ VIIA converts X-> Xa which will convert II(prothrombin) to IIa(thrombin) which will cleave VIII to vWF, activate VII, and activate platelets
Term
Regulation of Hemostasis
Definition
-primary and secondary hemostatsis dont stop spontaneously.
-can become a thrombosis if unchecked and other injuries can become uncontrollable hemorrhages.
-hemostatis is controlled by by anticoagulant proteins--that dampen coagulation cascade and by fibrinolysis, which degrades fibrin and recanulates vessels.
-Anticoagulant proteins inhibit procoagulant proteins
-Fibrinolysis-fibrin is formed then lysed
Term
Anticoagulant Proteins
Definition
Antithrombin (AT)
a-2 macroglobulin
Tissue factor pathway inhibitor
Term
Antithrombin (AT)
Definition
-70% of anticoagulant activity in plasma
-Heparin at endothelial surface complexes with AT
-inactivates IXa, Xa, XIa, XIIa
-very small protein and leaks through injured glomeruli
-glomerulopathies=huge loss of AT w/ subsequent thrombosis
Term
a-2 macroglobulin
Definition
-20% of anticoag activity in plasma
-inhibits thrombin, plasmin, and kallikrein
Term
Tissue factor pathway inhibitor
Definition
-circulates in small amount in plasma
-inhibits activated factor Xa that diffuses from site of vascular injury
Term
Fibrinolysis
Definition
fibrin is formed by axn of coagulation system is dissolved.
*important because: after hemorrhage, fibrin needs to be removed for healing and need to keep clot size in check..if too big--thrombosis can form.
-performed by plasmin to make fibrin degradation products.
-FDPs interfere with platelet fxn
Term
Plasmin
Definition
-formed from plasminogen (activated by XIIa and Tissue plasminogen activator and epithelial plasminogen activator), incorporated into clot as it forms.
-degrades fibrin (& fibrinogen) to peptides, small peptides and **d-dimer-only produced by covalently bonded fibrin, can be assayed to see if fibrinolysis is happening in body
Term
What can you assay to see if fibrinolysis is happening in the body?
Definition
d-dimer--degradation product of fibrin or fibronogen
Term
What can you assay to see if fibrinolysis is happening in the body?
Definition
d-dimer--degradation product of fibrin or fibronogen
Term
Laboratory evaluations of hemostatsis
Definition
Platelet count, Bleeding time, Activated Clotting time, Activated partial thromboplastic time, Prothrombin time/one-stage prothrombin time, Thrombin time, Plasma fibrinogen concentration, Assays to assess concentrations
Term
Disorders of Hemostasis
Definition
Vascular abnormalities, platelet abnormalities, disorders of coagulation system, combined disorders
Term
Platelet Count
Definition
-in CBC or individually by automated instruments, unopettes, monolayer of blood film
-if clump in blood=wont be counted as platelets
*normal=8 platelets/field, low=<8...look at feathered clumps, high=thrombocytosis-not a big deal.
Term
Bleeding time
Definition
fxnal test, measure cessation of blood flow, usually buccal mucosa (shallow puncture wound), remove blood every 30 sec, time ends when bleeding stops
**animals w/ abnormal bleeding times often have petechial hemorrhages
Term
what can cause increased bleeding time?
Definition
-blood vessel abnormalities (esp abnormal subendothelial collagen)
-thrombocytopenia
-abnormal platelet fxn
Term
Activated Clotting Time (ACT)
Definition
Tests the intrinsic and common systems
Term
Collecting for ACT test
Definition
-may be affected by severe thrombocytopenia
-WHOLE blood collected in warmed vacutainer tube w/ diatomaceous earth (activates factor XII & XI).
-make sure not contaminated w/ tissue thromboplastin (activates extrinsic system) found in extravascular tissue fluid.
-time stops when see a soft clot
-need phospholipid, if platelet <10,000 amt of phosopholipid is inadequat eand prolong time
Term
Activated partial thromboplastic time (APTT)
Definition
Tests the intrinsic and common system
Term
Collection for APTT test
Definition
-Calcium (contact activator) and phospholipid are added to citrated plasma from patient.
-contact activator activates factors XI and XII and extrinsic common systems prod fibrin
Term
Prothrombin time (PT)/ One-stage prothrombin time (OSPT)
Definition
Tests the extrinsic and common systems
Term
Collection for PT/OSPT test
Definition
-Calcium and tissue thromboplastin added to citrated plasma, extrinsic system activated when tissue thromblastin complexes with factor VIIa..activates factor X in common system..fibrin is produced.
Term
Thrombin Time (TT)
Definition
tests quantity of fibrinogen and functionality of fibrin
Term
Collecting for TT test
Definition
add thrombin and calicum to citrated plasma...thrombin with Ca will convert fibrinogen to fibrin.
-normal TT=normal plasma fibrinogen concentration
-increased TT=decreased plasma fibrinogen concentration...may result from increased consumption of fibrinogen (DIC) or decreased prod of fibrinogen (hepatic failure)
Term
Plasma fibrinogen concentration
Definition
masured by heat precipitation or immunologic methods (more accurate)
Term
Assays to assess concentrations of individual coagulation factors
Definition
need to go to laboratory, citrated plasma samples required
Term
Vascular disorders resulting in hemorrhage are inherited or acquired
Definition
Interited-Ehlers-Danlos syndrome=abnormal collagen formation leads to decreased platelet adhesion. rare.
Aquired: Vasculitis (inflammation of vessel wall disrupts vascular integrity. from immune mediated disorders->ag-ab complexes). Scurvy (vit C deficiency=deficient collagen formation causes decreased platelet adhesion and hemorrhage). Cushing's syndrome (decreased collagen prod causes hemorrhage b/c decreased platelet adhesion)
Term
Typical lab with hemorrhaging animals from vascular disorders
Definition
bleeding time=prolonged
act=normal
aptt=normal
pt=normal
tt=normal
Term
Platelet disorders resulting in hemorrhage
Definition
Thrombocytopenia,
Term
von Willebrand's disease is a disease of the primary or secondary hemostatic system?
Definition
primary
Term
Contents in a platelet (granule contents)
Definition
fibrinogen, calcium, von willibrand facotr, adenosine diphsophate
Term
Granule conents stimulate
Definition
aggregation of platelets and formation of a platelet plug
Term
Three differentials for erros in primary hemostasis
Definition
problem with the vessel
deficiency in platelet # or fxn
von Willebrand's disease
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