Coagulation Flashcards
(58 cards)
1
Q
Describe the cascade model of coagulation
A
2
Q
What are antiplatelet and anticoagulant factors the endothelium produces?
A
Antiplatelet:
* Prostacyclin
* NO
Anticoagulant:
* Antithrombin
* thrombomodulin
3
Q
What are the 3 phases of the cell-based model of coagulation?
A
- Initiation
- Amplification
- Propagation
4
Q
What is the major initiating trigger factor for hemostasis in the cell-based model of coagulation?
A
tissue factor bearing cells
5
Q
Name 3 causes of PLT sequestration
A
- Splenic torsion
- Hypersplenism
- Severe hypothermia
6
Q
Name 4 causes of PLT consumption
A
- acute hemorrhage
- DIC
- Sespsi
- Microangiopathies/vasculitis
7
Q
Nem 6 causes of increased PLT destruction
A
- Primary ITP
- Secondary TIP
–> Septic focus
–> Neoplasia
–> Vaccination
–> Drug reaction
–> vector-borne disease associated (Ehrlichia, Anaplasma, Rickettsia rickettsii, Dirofilaria immitis)
8
Q
Name 6 causes of decreased PLT production
A
Primary marrow disease
* infectious
* neoplastic
* immune-mediated
* idiopathic
* toxic/drugs
* radiation
9
Q
Name 7 causes of aquired intrinsic platelet dysfunction
A
- platelet inhibitors
- uremia
- synthetic colloids
- myeloproliferative disease
- pit viper envenomation
- DIC
- trauma-induced coagulopathy
10
Q
Name 5 causes of inherited intrinsic platelet dysfunction
A
- glanzmann thrombasthenia
- Scott syndrome
- CHediak-Higashi syndrome
- Cyclic hematopoiesis
- selective ADP deficiency
11
Q
Name 1 cause of inherited extrinsiv platelet dysfunction
A
vWD
12
Q
What is the platelet crit (PCT)?
A
overall PLT mass
13
Q
Whar are normal BMBT in dogs and cats? What other factors apart from PLTs affect BMBT? What analyzer provides similar information as the BMBT?
A
Dogs: <3min
Cats: <2min
- HCT
- blood viscosity
–> platelet function analyzer-100 (PAF-100)
14
Q
What platelet function analyzer can be used clinically?
A
- Whole blood multiple electrode impedance aggregometry
Others in research:
* flow cytometry
* optical aggregometry
15
Q
How are PT and aPTT measuresd?
A
PT = addition of tissue factor
aPTT = addition of koalin + source of phospholipids
16
Q
What information does viscoelastic testing provide?
A
- rate of clot formation
- clot strength
- rate of fibrinolysis
17
Q
What (apart from hemostatis function) impacts TEG?
A
plasma proteins, but not PCV
18
Q
Name 11 causes of acquired secondary hemostasis disorders.
A
- Vitamin K deficiency
- Vitamin K antagonism
- Liver dysfunction
- Citrate overdose
- Severe hypothermia
- Acidemia
- Anticoagulants
- hemodilution
- DIC
- trauma-induced coagulopathy
- Angiostrongylus vasorum infection
19
Q
Name 10 causes of inhered secondary hemostasis disorders.
A
- Factor I: Hypofibrinogenemia, dysfibrinogenemia
- Factor II: Hypoprothrombinemia
- Factor VII: Hypoproconvertinemia
- Factor VIII: Haemophilia A
- Factor IX: Haemophilia B
- Factor X: Stuart-Power trait
- Factor XI: Plasma thromboplastin antecedent deficicency
- Factor XII: Hageman deficiency
- Vitamin K- dependent factor deficiency (II, VII, IX, X)
- Prekallikrein deficiency
20
Q
Give an overview of all 4 different viscoelastic testing devices and what they measure.
A
21
Q
What affects reaction time (RT - TEG)/clot time (CT - ROTEM/VCM)?
A
FXII
FXI
22
Q
What affects Kinetiks (K-TEG)/clot formation time (CFT - ROTEM/VCM)?
A
Fibrinogen
FXIII
PLT
23
Q
What affects the alpha angle?
A
Fibrinogen
FXIII
PLT
24
Q
What aeffects the maximum amplitude (MA - TEG)/maximum clot firmness (MCF - ROTEM/VCM)?
A
PLT
fibrinogen
25
What is G and how is it calculated (TEG)?
G = elastic shear modulus
Difference to MA:
* reflects the mechanical strength (resistance to shear) of the clot — this is a physical property, not just a tracing width.
* It’s on a logarithmic scale — meaning it amplifies changes in clot strength that might not be obvious with MA.
--> affected by PLT + fibrinogen (like MA)
G = 5000xMA/(100-MA) = dynes/cm²
MA...measured in mm
26
What affectes clot lysis (lysis index in VCM) (LY30/60)?
plasmin activity
27
How can aspirin be monitored?
* PFA-100 (using collagen epinephrine)
* Platelet aggregometry (arachidonic acid)
* TEG-platelet mapping (arachidonic acid)
28
How can clopidogrel be monitored?
* PFA-100 (using ADP-collagen)
* platelet aggregometry (ADP)
* TEG-platelet mapping (ADP)
29
How can warfarin be monitored?
* INR
* aPTT
30
How can UFH be monitored?
* Drug specific anti-Xa activity
* PT
* ACT
* TF + koalin activated TEG (RapidTEG)
31
How can LMWH be monitored?
* durg specific anti-Xa activity
32
How can oral Xa-inhibitor (e.g. rivaroxaban) be monitored?
* drug specific anti-Xa activity
* PT
33
When is spontaneous or procedural bleeding unlikey in case of thrombocytopenia? How does this change with recovery?
> 50000/µl
Recovery: 20-50000/µl
34
What indices may provide an earlier indication of PLT recovery than PLT count?
* PCT
* MPV
35
What characterizes a coagulopathy induced by synthetic colloids?
* acquired vWF deficiency
* FVIII deficiency
36
What are clotting factors?
= serine proteases, which are released as zymogens and require activation to exert biological effect
37
Why do anticoagulant rodenticides induce a coagulopathy?
--> inhibit Vitamin K epoxide reductase, an enzyme important for vitamin K recycling. Hydroquinone (= reduced Vitamin K) must be present for activation of the vitamin K-dependent coagulation factors (II, VII, IX, X)
38
Why does Vitamin K deficiency cause a coagulopathy?
Hydroquinone (= reduced Vitamin K) must be present for activation of the vitamin K-dependent coagulation factors (II, VII, IX, X)
39
Why is the liver important for coagulation?
clotting factors, endogenous anticoagulants (e.g. protein C) and fibrinolytic proteins are all synthesized in the liver
40
What are the underlying causes of coagulopathy in liver disease?
1. reduced factor synthesis
2. Vitamin K deficiency
3. acquired PLT dysfunction
4. hyperfibrinolysis (in acute liver failure, not in chronic)
41
What hemostatic change has been identified in acute liver dysfunction, that may not be present in chronic hepatopathy?
Hyperfibrinolysis
42
What hemostatic change has been reported to be present in PSS patients?
Hypercoagulability
43
Discuss the 2 phases of DIC
Nonovert DIC: Early --> hypercoagulability
precipitating trigger (e.g. inflammation, sepsis) --> systemic activation of coagulation --> massive thrombin generation + widespread clot formation --> microthrombosis --> tissue hypoperfusion
Overt DIC: late --> hypocoagulability
as consumption continues --> more bleeding tendency
44
What are potential hemostatic abnormalities that occur in DIC?
* thrombocytopenia
* prolonation of PT and aPTT
* elevated D-Dimer
* Hypofibrinogenemia
* reduced antithrombn activity
45
What are 2 factors assocaited with hyperfibrinolytic tendency in dogs with spontaenous haemoperitoneum?
* hyperlactatemia
* greater volume of plasma administration
46
What are the 3 categories of treatment for coagulopathies in critically ill patients?
1. administration of transfusion products
2. hemostatic agents
3. therapy aimed at primary disease
47
In what disease states are lysin analogs like TXA not recommended?
* DIC
* if blood clots could lead to obstruction (urinary bladder hemorrhage, airway hermorrhage)
48
What are the 3 main causes for hypercoagulability?
* increased procoagulant elements
* decreased anticoagulant elements
* diminished fibrinolysis
49
What is Virchow's triad?
1. Hypercoagulability
2. blood statis or altered blood flow
3. Endothelial dysfunction
50
What are the anticoagulant functions of the endothelium?
* Heparan sulfate on glycocalyx facilitates binding of ATIII (50-90% of proteoglycanes) --> AT-mediated inhibition of thrombin
* heparan cofactor II (anticoagulant) bind on GC
* Tissuemodulin (anticoagulant) bind on GC
* mechanoceptors on GC lead to release of NO during shear stress --> inhibition of platelet aggregation
51
How does inflammation change the anticoagulant functions of the Glycocalyx?
* decreased synthesis of GAG --> compromise GC --> decreased function of anticoagulants that need glycocalyx (thrombomodulin, protein C, TFPI)
* release of ultra-large vWF --> binds platelet GPIba receptor --> platelet tethering + activation
* decreased ADAMTS-13 --> decreased cleavage of ultra-large vWF --> systemic platelet aggregation, thrombosis --> consumptive thrombocytopenia
52
What is ADAMTS-13?
enzyme that usually cleaves ultra-large vWF into smaller vWF molecules that can circulate freely in association with FVIII --> smaller vWF have less platlet aggregatory acticity --> less pro-coagulant
53
What increased procoagulant elements exist, that can lead to a hypercoagulable state (apart from endothelial injury)?
1. increase in circulating tissue factor (also expressed on neoplastic cells, monocytes/macrophages)
--> activates NF-Kb --> production of TNFa --> perpetuates inflammation
2. PLTs: --> shape change upon activation --> shuffling of negatively charged phospholipids to the surface (PS, PE) --> catalytic surface for propagation of clot formation (tenase + prothrombinase complexes)
3. PLT increase number of fibrinogen receptor (integrin a2nb3) on surface
4. PLT release granules containing procoagulant elements like Ca2+, FVa, serotonin, P-selectin, ADP
5. Microparticles released from activated or apopototic cells --> express TF + have vWF binding sites
6. NETs --> activation of contact pathway + platelet activation + impaired fibrinolysis
54
What decreased endogenous anticoagulant changes exist in inflammtion?
1. Decreased AT due to increased consumption (thrombin generation), decreased production (negative acute phase protein), increased degradation by NE or urinary loss in glomerulonephritis
2. decreased hepatic synthesis of protein C and S
3. hindered activation of protein C via effects of cytokines on endothelium + Thrombomodulin (downregulation of TM expression due to TNFa + increased cleavage of TM from endothelium via elastases from endotoxin-activated neutrophils)
4. Decreased TFPA activatoin
55
What are the 3 primary anticoagulants?
1. protein C
2. ATIII
3. TFPI
56
What is the function of ATIII?
1. inhibition of thrombin + factor Xa (!)
2. inhibition of FIXa + FVIIa-TF complex
--> most effective when bound to heparin-like GAGs of GC or when exposed to exogenous heparin --> increases inhibition of thrombin greatr than 1000 fold
57
How does protein C mediate its anticoagulant action?
Thrombin bind to Thrombomodulin on endothelium --> activation of Protein C (accelerated in presence of endothelial protein C receptor
58
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