Chapter 7 Bleeding and Hemostasis Flashcards
What are platelets roles in primary hemostasis
- Platelet adhesion
- Shape change
- Granule release of TXA2 and ADP
- Recruitment
- Aggregation (platelet plug)
Describe platelet adhesion
Platelets adhere to subendothelial collagen via platelet glycoprotein VI or vWF via glycoprotein Ib receptor
What triggers shape change during primary hemostasis
Adherence of platelets to subendothelial collagen and/or vWF
What is released during activation in primary hemostasis
Secondary agonists - TXA2 and ADP via arachidonic acid metabolism
Which coagulation test most closely reflects in vivo hemostasis?
TEG
D-dimer
Indicates activation of thrombin and plasmin and are specific for active coagulation and fibrinolysis
Which tests evaluate the intrinsic pathway
APTT - if prolonged then defective intrinsic or common pathway
ACT - less sensitive but also evaluates both
Which test evaluates the extrinsic pathway?
PT
Which test is most sensitive to vitamin K deficiency
PT
What are the three phases of coagulation
Initiation
Amplification
Propagation
What is generated in the initiation phase
Thrombin
What occurs during amplification phase
thrombin amplifies signal and sets stage for procoagulant complex assembly
What occurs during propagation?
Complexes assemble on the surface of activated platelets and large amounts of thrombin and fibrin are generated.
What is the product of Initiation
thrombin
Factors involved in amplification
Plt activated by thrombin produced in initiation phase
PLT are activated and have activated cofactors V and VIII
Factors involved in propagation
fXI activated by thrombin —> fXIa
fXIa generates fIXa
[fIXa + tissue factor bearing cells + fVIIIa] = activates fX —> fXa
Common pathway: [fXa + fVa] activate prothrombin into thrombin to cleave fibrinogen into large amounts of fibrin
What are three natural anticoagulants
Antithrombin
Protein C
Tissue factor inhibitor
Natural anticoagulant - Antithrombin moa
Circulating alpha-globulin* produced in the liver
Binds and inactivates thrombin fIXa, fXa, fXIa, and fXIIa *
Natural anticoagulant - Protein C (and cofactor S) moa
Inactivate cofactors fVa and fVIIIa and slows thrombin formation
Natural coagulant - Tissue factor inhibitor moa
Binds and inactivates FXa and fVIIa-tissue factor
Antiangiogenic and antimetastatic properties
What type of von willebrands disease would benefit from desmopressin
Type I
vWF effects of DAVPP
Desmopressin can be used as adjunctive therapy in dogs with type 1 vWD during bleeding crisis or can be prophylactically given 30 min before surgery. Usually maximal response achieved 1-2 hours after dosing.
Response: increased [vWF] and factor VIII and shortened bleeding times likely from release of vWF and factor VIII from endothelial stores
Also works in dogs on aspirin
vWD ELISA
Definitive diagnosis of vWD requires determination of vWF levels via ELISA.
< 50% is considered deficient. Differentiation between type 1 and 2 requires determination of multimer distribution via immunoelectrophoresis
vWF role
Serves as an adhesion bridge between subendothelial collagen and glycoprotein Ib platelet receptor
Adherence to glycoprotein Ib platelet receptor triggers shape change, stimulation of arachidonic acid metabolism, and release of granular contents (activation)
What blood product is given to patients with vWD prior to surgery and how long does it last?
Cryoprecipitate
Concentration elevated within 30 minutes and remains elevated for 4 hours.
What factors are in cryoprecipitate?
Factor VIII, vWF, fibronectin, and fibrinogen
Plavix MOA
ADP antagonist: active metabolites irreversibly block ADP from binding to its receptor on the PLT (PY2) preventing activation of alpha IIb Beta 3 intern, fibrinogen binding, and aggregation
How long does it take for platelet inhibition when giving plavix?
Inhibition occurs in 2-5 days
How long prior to surgery should plavix be discontinued?
7-10 days
Describe bleeding in greyhounds or sight hounds
1/3 of clinically normal greyhounds may develop delayed bleeding up to 3 days after elective surgery due to altered fibrinolysis
Why are dogs with HAC (Cushing’s) susceptible to thromboembolic events?
COX-2 inhibition by endogenous glucocorticoids may cause increase risk of thrombogenesis in dogs with HAC
Which tests are for primary vs secondary hemostatis
Primary - BMBT and platelet count
Secondary - ACT, PT, PTT
