7 Flashcards
2 stages of hemostasis
- primary hemostasis–platelet plug2. secondary hemostasis–proteolytic clotting cascade; fibrin clot/mature thrombus
platelet characteristics
anucleatemegakaryocyte precursorlife span 6-8 days
prostaglandin responsible for platelet aggregation/activation
thromboxane (TxA2)made from AA–>cox 1 pathway
platelet MOA after endothelial injury
- adhere to exposed endothelial collagen via vWF2. activation which leads to granular release (TXA2, ADP) and conformational change exposing binding domains for fibrinogen3. recruitment4. aggregation
cascade model of coagulation INTRINSIC
XII converts XI activeXI with VIII, PL, Ca activate IXCOMMONIX activates X X with V, PL, Ca activate THROMBINthrombin converts fibrinogen to fibrinaPTT
cascade model of coagulation
TF +PL, Ca activate VIICOMMONVII activates XX with V, PL, Ca activate THROMBINthrombin converts fibrinogen to fibrinPT
clotting number of thrombin
II
theory behind cell based model of coagulation
- TF is primary physiologic activator/initiator2. coagulation is localized to and controlled by cell surfacesinitiation, amplification, propagation
normal inhibitors of platelet reactivity
Prostacyclin (PGI2)NOectoadenosine diphosphatase
Three natural anticoagulant pathways
antithrombin IIIactivated protein CTF inhibitor
MOA of antithrombin III
AT III binds and inactivates factor 10 of the common pathwayalso neutralizes other clotting factors, antiinflammatoryactivity of AT III is increased with the presence of heparin
MOA of activated protein C
activated protein C inhibits VII, Vdecreases thrombin formationenhances fibrinolysis
MOA TF inhibitor
inhibits TF of extrinsic pathway
fibrinolysis
dissolution of fibrin clotmain proteolytic enzyme = plasminogen –>plasmindegrades fibrin to FDP, FSPother enzyme: tissue type and urokinase type plasminogen activators
how is fibrinolysis controlled
plasminogen activator inhibitorsalpha antiplasminthrombin activator fibrinolysis inhibitor
cause of pseudothrombocytopenia
falsely low due to platelet aggregation and mis countingreported in 71% of feline blood samples
estimate of average platelet count on blood smear
platelets/HPF x 15,000
BMBT
buccal mucosal bleeding time–tests platelet fx/primary hemostasisN dog 1.7-4.2 minN cat 1.4-2.4 mininter/intraoperative variability up to 2 min
BMBT is prolonged with what diseases
thrombocytopeniathrombocytopathia (vWF disease)vasculopathy
what % of coagulation factors must be decr to have prolonged PT/aPTT
25-30% decreased prior to prolongation
vitamin K dependent coagulation factors
2, 7, 9, 107 has the shortest half life
what coagulation test to examine for bit K deficient animals
PT7 because of very short half life 4-6 hr
PT tests…
extrinsic + common pathwayTF, 7less sensitive to heparin affects than aPTT
aPTT tests…
intrinsic + common12, 11, 9
activated clotting times ACT
whole blood + diatomaceous earth (contact factor for XII)tests INTRINSIC and common pathN dog < 110 sN cat < 75 sless sensitive than aPTT
FDP/FSP
degradation products of fibrin/fibrinogenmarkers of fibrinolysisusually cleared via livercan lead to dysfx in platelets/inhibit coagulationMay be a marker DIC
D dimers
indicate activation of thrombin and plasminspecific for activation of coagulation and fibrinolysissensitive marker for DIC, thromboembolism with excellent negative predictive valueNOT specific
fibrinogen deficiency in relation to thrombin clot time
TCT is prolonged and clot formation decreased with 1. hypofibrinogenemia2. dysfibrinogenemia3. presence of factors inhibiting fibrin polymerization (heparin, FDPs)
list coagulation testing
platelet number and blood smear reviewPT/PTTBMBTACTFDPs/FSPsDDimersFibrinogenTEG
Thromboelastography
TEG evaluations clot initiation, formation, propagation to fibrinolysisstrength and stability of clotdynamics of its formation and breakdown
TEG parameters
R reaction time (time of latency until start of clot form)K clotting time (time to clot formation)alpha how fast clot is formedMA max amplitude (overall strength of clot)LY60 (fibrinolysis)
which TEG variable measures secondary hemostasis
R reaction time (time of latency until start of clot form)
Which TEG variable measures clot kinetics
K clotting time (time to clot formation)
predictive value of TEG to ID bleeding
TEG correctly ID bleeding with PPV 89% NPV 9*%
disorders of primary hemostasis
thrombocytopenia (SPUD)thombopathia (acquired, inherited-vWF)vasculopathy (acquired, inherited-ehler-danlos)pg 101
acute coagulopathy of trauma
tissue injury, shock, massive fluid resuscitation (>blood volume within 24 hr)hemodilutionhypothermiaacidemiashock
what is the first factor to be decreased with hemodilution
fibrinogen
which fluid demonstrates the most pronounced hemodilution effect
hetastarchdecreases fibrinogen, vWF, VIII
clinical signs of patients with primary hemostatic disorder
ecchymosisspontaneous bleeding from mucosal surfacespetechia (more with thrombocytopenia rather than pathia)
clinical signs of patients with secondary hemostatic disorder
hematomasbleeding into body cavity
indications for use of cryoppt
vWF disease VIII deficiencyhypofibrinogenemia/dysfibrinogenemia
list platelet containing blood products
fresh whole blood**platelet rich plasmaplatelet concentrate
T/FDesmopressin is effective for all types of vWF
FALSEonly effective for type I vWF were there is not a complete absence of vWF
treatment of hemophiliac patients
recombinant factor VIIpromotes extrinsic/common pathway especially important for hemophilia A (8) and B (9) deficiencies of the intrinsic pathwayDOSE CANNOT BE REPEATED–Ab develop
most common primary hemostatic disorder
thrombocytopeniaSPUD (immune mediated destruction is most common cause in dogs)may not have spontaneous bleeding until < 50,000
condition of non pathologic thrombocytopenia
Cavalier King Charles Spaniel
most common congenital bleeding disorder
vWF deficiency (ELISA definitive dx 50% cut off)1. all multimers present but reduced concentration–DOBIES2. loss of hi moleculecular weight multimers–GSP GWP3. absence all multimers–sheltie, bay retrievers
most common inherited coagulopathy in cats
deficiency in factor 12does not result in bleeding usuallyprolongation aPTT
% of dogs and cats with hepatobiliary disease that have some sort of hemostatic abnormality
dog 93%cat 82%spontaneous bleeding occurs in < 2%
T/Fvit K trial therapy is advantageous in patients with cholestatic/liver disease
TRUEliver responsible for vit K metabolismdysfunction leads to malabsorption of vit K which leads to decr clotting factors 2, 7, 9, 10may see prolongations of PT (due to factor 7)
what is Virchow’s triad in thromboembolic discussion
thrombotic tendency depends on 3 major risk factors1. endothelial injury2. blood stasis3. hypercoagulability
a study of dogs with THR show what % of thromboembolism
82%
what is oligemia in terms of diagnosing pulmonary thromboembolic disease
oligemia increased radiolucency on VD/DV thoracic filmscorresponds to hypovascular area of lung regions distal to PTE
Diagnostics for PTE patient
D DimersTEGRadiographs (nonspecific; oligemia)ABGCardiac eval/Echo (right hypokinesis)DEFINITIVE DX: selective pulmonary angiography
most common abnormalities in ABG of PTE patient
not pathognomonic (in descending order)1. increased Aa gradient2. hypoxemia3. hypocapnia4. decrease oxygen response
management of thromboembolic disease
- anti platelet drugs (aspirin, clopidogrel)2. anticoagulants (heparin–unfrac, LMW and warfarin)
drug protocol for hyperadrenocorticoid dogs undergoing adrenalectomy
unfrac heparin in plasma at induction followed by 35 U/kg SQ q8hr tapered over 4 days
drug used for prophy tx of emboli in renal transplants in dogs
low molecular wt heparin enoxaparin before sx0/5 w drug had TE5/10 dogs without drugs had TE
diagnosis of DIC
3 or more of the following:thrombocytopeniaPT/aPTT prolongationincr FDPs/ D Dimershypofibrinogenemiadecreased antithrombin III activityRBC fragmentation
most dogs with DIC are hyper or hypo coagulable?
HYPER only 22% hypocoagulable
MOA of clopidogrel
blocks ADP binding to receptor on platelet (P2Y12)prevents activation/recruitment/aggregation
what is the target aPTT when treating for thromboembolic disease
aPTT 1.5-2.0 times normal
