Bleeding and Hemostasis Flashcards
What are the most common causes of DIC in dogs/cats?
Dogs: sepsis/SIRS
Cats: neoplasia then pancreatitis
What is the strongest predictor of nonsurvival with acute traumatic coagulopathy (ATC)?
APTT
Warfarin:
MOA?
Adv?
Disadv?
Monitor with?
Vit K antagonist -> 2,7,9,10 protein C/S
Adv: once daily oral dose, cheap
Disadv: low therapeutic index, PK influenced by diets, comorbidities, drugs, needs strict owner compliance
Monitor: PT adjust dose to get PT 1.25 to 1.5 times baseline
List tests that can definitively diagnose venus thromboembolism (TE?)
Gold standard is selective pulmonary angiography
Pulmonary scintigraphy
CT pulmonary angiography
How does hepatic disease contribute to both thrombopathy and hypercoagulability?
Thrombopathy: platelet defects, imparied signalling, decreased THA synthesis, storage pool defects, increased inhibitors (bile acids etc)
Hypercoagulability: decreased synthesis of antithrombin and activated protein C + portal hypertension(change in blood flow)
Congenital PSS -> hypercoag on TEG
Desmopressin:
MOA?
Duration of effect?
Treats?
Synthetic vasopressin induces release of vWF from stores -> increased platelet function by increasing vWF, FVIII, plasminogen
Duration of action: 2 hours
Treats: Type 1 vWD, acetylsalicylic acid coagulopathies NOT Type 2/3 vWD
What are the three major inhibitors of the fibrinolytic system?
Plasminogen activator-inhibitor (PAI-1), TAF-1 and alpha2-AP (stored in platelet granules)
What breed of cat has Vit K dependent factor deficiency?
What factor is most commonly deficient in cats?
Devon rex
XII
Clopidogrel:
MOA?
Side effects?
Blocks ADP binding to P2Y12 receptor on platelet surface -> prevents activation of integrin, fibrinogen binding, and sustained aggregation
Also inhibits serotonin release which decreases the ischemic impact of thromboembolism.
Side effect is (D) in cats?
Heparin:
MOA?
Sizes of unfractionated/low molecular weight?
Adv of low molecular weight?
How do you monitor?
MOA: inactivates Factor II (thrombin) and Factor Xa
Unfractionated = 5,000 to 30k daltons thrombin > Xa inhibition
LMWHeparin = 4k-6500 da Xa > thrombin effects
Adv: prolonged half life, more predictable responses and renal clearance
Monitor with TEG for LMWH, use APTT for unfractionated
Aspirin:
MOA?
pharmacokinetics?
Side effects?
inactivates COX-1 -> suppresses TXA2 -> irreversible platelet dysfunction (must wait for new PLT)
onset rapid, antithrombotic effect blocked by parallel inhibition of prostacyclin which is prothrombotic
side effects are GI lesions, (D), w/steroids
What is Virchow’s Triad?
The three risk factors for thrombosis
- endothelial injury
- vascular stasis
- hypercoagulability
Activated clotting time tests what?
How is it performed?
Intrinsic and common pathways
- whole blood + celite, kaolin, glass beads to activate FXII
What are the types of vWD?
How do you diagnose it?
Type 1 vWD has all multimers but low concentration -> Dobermans
Type 2 has a disproportionate loss of the high MW multimers (German Pointers)
Type 3 is an almost complete absence of vWF -> they are high risk of life threatening hemorrhage (sheepdogs, scottish terriers, chessies etc.)
Diagnosis: ELISA is gold standard with <51% being deficient, a BMBT is an indirect test for it.
What are the 4 technical causes of bleeding?
- Inadequate repair of vessels or vascular structures opened
- Occult or undiagnosed
- Damage to structures in the operative filed during surgery
- damage during the course of surgery to structures remote from the surgery site
TEG:
At what temp is the sample set?
oscillated through angle of ____?
How long should your test wait (max)?
What are the things measured with TEG?
37C
4 degrees 45’
Perform test <30 min from sampling
R = reaction time -> indicates fibrin formation
K = clotting time
Angle alpha: slope of R to K
Max amplitude = ultimate strength of clot
G = clot shear elastic modulus “overall status”
Explain the three phases of the cell model of coagulation:
Initiation = extrinsic (generates thrombin!)
- TF on fibroblasts
-fVIIa and fVa produce thrombin (fIIa)
-fIIa-TF complexes activate fIX
Amplification = platelets adhered in proximity to TF bearing cells
-Activated by thrombin from initiation phase
-fV activated by thrombin
-vWF/fVII binds to activated platelets and activates fVIII / releases more vWF
Propagation = fXI binds and activated by thrombin and makes fXIa which complexes with fVIIIa to stimulate fX. Xa-Va activate prothrombin -> thrombin -> fibrin
What is in cryoprecipitate?
What does it primarily treat?
vWF, fVIII, fibrinogen, fibronectin
treats hypofibrinogenemia, vWD, hemophilias
After giving one blood volume of platelet -deficient fluid, how much platelets remain in circulation?
35-40%
What is the MOA of Yunnan Baiyao?
increased expression of surface glycoproteins on platelets -> shortened bleeding times
What is needed in order to have coagulation proceed?
Tissue factor (TF)
Which test is best to predict surgical bleeding?
What does that test not detect?
TEG
It doesn’t detect thrombopathies of vWD
Prolonged PT indicates what?
Prolonged APTT indicates what?
How much do factors need to decrease for prolongation to occur?
Which test is sensitive to vitamin K deficiency?
What are disadvantages of PT/APTT?
Extrinsic/common issue
Intrinsic/common issue
down to 25-30%
PT
Do not assess hypercoagulability and cannot accurately predict bleeding
How do the following contribute to acute trauma coagulopathy (ACT)?
- tissue injury/hypoperfusion
- inflammation
- acidemia
- hypothermia
- hemodilution
tissue injury/hypoperfusion -> exposes collagen to vWF and TF to fVII etc
inflammation -> TNF-a IL-1/6 complement etc
acidemia -> pH<7.2 increases the degredation of fibrinogen and impairs coag activity (giving buffers does not reverse this)
hypothermia -> temp <33C decreases platelet function and activity of fVII/TF complex
hemodilution -> decreases vWF/fVIII, decreases fibrinogen, shift of coag deficient fluid to the plasma
The lifespan of platelets is ___days in cat/dog?
How many platelets are released per day?
6-8 days
10’
What are the most common causes of venous TE in dogs/cats?
Dogs: PLN, neoplasia, IMHA, necrotizing pancreatitis
Cats: heart disease, neoplasia
An increased MA on TEG test indicates what?
What does a decreased R indicate?
Increased MA = platelet hyperaggregability
Decreased R = enzymatic hyperactivity
What are some blood gas changes seen with venous TE?
Increased A-a gradient, hypoxemia (O2 responsive), hypocapnia
The cascade model of coag is all initiated from which factor?
XII
What are secondary antagonists that recruit more platelets?
vWF to start -> TXa2/ADP are secondary agonists
What is the suspected mechanism for post-op bleeding in greyhounds?
Fibrinolysis
What bleeding condition is not treatable with fresh frozen plasma? Why?
Heparin-induced bleeding because it is caused by a factor inhibitor, not a deficiency -> new factors just get inhibited. Also antithrombin may actually enhance effects of heparin.
What 3 components in endothelium control platelet activity?
Prostacyclin (PGI2); ectoadenosine diphosphatase (ectoADPase); nitric oxide (NO)
What are 3 natural anticoagulant pathways?
Antithrombin, activated protein C, tissue factor pathway inhibitor
What are different factors that contribute to fibrinolysis?
t-PA (endothelial cells),u-PA, FDPs, thrombin activatable fibrinolysis inhibitor (TAFi), A-2 antiplasmin (A2-AP)
At what value x normal do increases in PT/APTT indicate risk for hemorrhage?
1.5x normal
Patients with platelet counts < ____ suffer operative bleeding?
50,000
What is in frozen plasma?
Factors II, VII, IX, X, albumin and globulins
What breed can be known to have low platelet counts?
Cavalier King Charles Spaniel
How are d-dimers helpful?
When is it not helpful?
Sensitive indicator for thrombotic conditions like DIC and PTE
- specificity/sensitivity is low for CATS
What test is used to look at fibrinogen?
Thrombin clot time or thrombin time
How does decreased albumin cause increased platelet hypercoagulability?
TXA2 synthesis is increased
Hemophiliacs have what factor deficiencies?
VIII, IX
What does a coag panel look like for vitamin K deficiency?
Increased PT first, then increased APTT
FSP, d-dimer, fibrinogen and platelet counts are normal.
Decreased factor synthesis requires how much liver dysfunction?
> 70% decrease in functional hepatic mass
How do you estimate platelet count on a smear?
Number of platelets per HPF x 15,000
BMBT tests for what?
What elevates BMBT?
Primary hemostasis
Thrombocytopenia, thrombopathia, vasculopathy
How does endothelial thrombomodulin help control fibrinolysis?
Activates protein C comlex (pro-fibrinolysis and anti-coagulation) also stimulates fibrinolysis inhibitor?
Antifibrinolytics:
Examples?
MOA?
Indications?
Epsilon aminocaproic acid, tranexamic acid
-blocks binding/activation of plasminogen and exerts anti-inflammatory effects through IL-inhibition
Treats: greyhounds as pre-sx prophylaxis
minimal side effects
What 3 hypothesis contribute to ATC?
- DIC w/hyperfibrinolytic phenotype
- Enhanced thrombomodulin-thrombin protein C pathway
- Catecholamine-induced endothelial damage
What 6 factors influence development of ATC?
tissue injury, hypoperfusion, systemic inflammation, acidemia, hypothermia, hemodilution
What is the lethal triad or trauma triad of death?
coagulopathy, acidosis, hypothermia
What are the initiators of DIC?
TNF-a ; IL-6
What is generally seen in hemostatic tests for DIC?
deficiency in everything
