Secondary Hemostasis Flashcards
What is secondary hemostasis? Where does this occur?
coagulation by simultaneous activation of platelets and the coagulation system to produce a stable fibrin clot
sites of vascular injury
What 2 groups of things is coagulation dependent on?
- coagulation factors
- cells - fibroblasts, platelets, endothelial cells, leukocytes
Where are coagulation factors synthesized? What happens when this organ is diseased?
in the liver by hepatocytes
decrease in coagulation factors - coagulation factor concentration can give information about liver function
What are the 9 enzymatic coagulation factors?
- XIIa
- XIa
- IXa
- VIIa
- Xa
- prothrombin (II)
- thrombin (IIa)
- fibrinogen (I)
- fibrin (Ia)
What are the 5 non-enzymatic factors?
- tissue factor (III, thromboplastin)
- VIIIa
- Va
- calcium
- platelets
What are the vitamin K-dependent coagulation factors? Which has the shortest half-life?
II, VII, IX, X
(2+7 = 9 not 10)
VII
How does vitamin K activate coagulation factors?
activates precursors (procoagulants) by post-translational carboxylation of glutamine acid residues on the molecules
What happens in the coagulation cascade with low levels of vitamin K? What are 2 possible causes?
decreased production of functional clotting factors leaving them in their inactive state - PT, PTT, ACT will be abnormal
- coumarin-containing compounds - rodenticides, warfarin, moldy sweet clover
- fat malabsorption - inability to absorb fat-soluble vitamin K
Clotting factors:
What are the 2 parts of the coagulation cascade? Where do they meet?
- intrinsic - 12, 11, 9, 8
- extrinsic - tissue factor (II), 7
common pathway - 4, 10, 5, 2, fibrinogen, fibrin
What are the 4 steps to the extrinsic pathway? What does this result in?
- vascular damage causes the expression of tissue factor (II) from fibroblasts
- II reacts with F7 to become F7a
- F7a + calcium activates 10 into 10a
- 10a begins the common pathway
small amount of thrombin (2a) is generated to begin the first stage of secondary hemostasis
How does the intrinsic pathway start? How does this happen?
thrombin from the extrinsic pathway is amplified and propagated
AMPLIFICATION: thrombin activates F11 into F11a —> F8 into F8a —> F5 into F5a
PROPAGATION: F11 (with calcium) cleaves 9 into 9a —> 10 into 10a to start the common pathway
What are the 3 steps of the intrinsic pathway?
- initiation begins when F12 is exposed to collagen
- F12a activates F11 into F11a
- F11a + Ca activates F9 into F9a
- F9a + F8 + Ca complex to activate F10
(a good deal in not buying at $12.00, it is buying at $11.98)
Where is Factor VIII usually found? How does this make it function in the coagulation cascade?
usually circulated as a non-covalent complex with vWF
vWF-bound F8 cannot participate in the intrinsic pathway of coagulation
What are the 4 steps to the common pathway?
- F10 is activated via intrinsic or extrinsic pathways
- 10a and thrombin (2a) from extrinsic pathway activates 5 into 5a
- 10a + 5a + Ca activate prothrombin (2) into thrombin (2a)
- thrombin cleaves fibrinogen (F1) into fibrin (1a) to form a soft clot (13a)
What is fibrinolysis? What is it necessary for?
enzymatic process that dissolved fibrin clot into fibrin degradation products using plasmin, which originates from fibrin-bound plasminogen in the liver
wound healing, reestablishment of circulation, and prevention of thrombosis
What initially stimulates fibrinolysis?
thrombin production during vessel injury
as a stable fibrin clot is formed, thrombin production decreases and fibrinolysis dominates
What activates plasminogen? What cells secrete this?
tissue plasminogen activator (tPA) cleaves plasminogen into plasmin
local endothelial cells
What does an increase in fibrin degradation products D-dimers indicate?
intravascular coagulation with clot breakdown
What 3 inhibitors are used to control the coagulation pathway? How do they work?
- tissue factor pathway inhibitor - inhibits formation of TF-7a complex
- anti-thrombin III - binds directly to inactivate thrombin, 9a, 10a, and 11a
- tissue plasminogen activator (tPA) - cleaves plasminogen into plasmin
Deficiencies of what 4 substances increase the risk of thrombosis?
- antithrombin (AT)
- thrombomodulin (TM)
- protein C
- tissue factor pathway inhibitor (TFPI)
Where is antithrombin produced? What 2 things does it inhibit? What increases its activity?
liver - accounts for 70% of anticoagulant activity in plasma
Factor Xa and thrombiin
heparin (1000x)
What 3 things cause antithrombin deficiencies?
- increased consumption (DIC)
- increased loss (protein-losing nephropathy)
- decreased production (liver disease)
Where is thrombomodulin produced? How does it work?
endothelial cells
binds to thrombin and decreases ability to form clots
Where is protein C produced? What activates it? What 2 functions does it have?
liver
thrombomodulin-thrombin complex
- inactivates F5a and F8a
- increases fibrinolysis by facilitating plasmin
How does tissue factor pathway inhibitor work?
forms a complex with F7a to inhibit the action of the F7a-TF complex
What are the 3 activators and inhibitors or fibrinolysis?
ACTIVATORS:
1. tissue plasminogen activator (tPA)
2. Factor XIa
3. Factor XIIa
INHIBITORS
1. α2-antiplasmin
2. plasminogen activator inhibitor (PAI)
3. thrombin (2a)
What tube is blood put into to evaluate its hemostasis? Why?
blue top tube with 3.2% sodium citrate
citrated plasma contains no RBCs, WBCs, or platelets and doesn’t contain much calcium (chelated)
What are the procoagulant tests? Anticoagulant tests?
PROCOAGULANT:
- activated thromboplastin time (aPTT, PTT)
- prothrombin time (PT)
- thrombin time (TT), fibrinogen
- PIVKA
- specific factor assays
ANTICOAGULANT:
- fibrinolytic activity: fibrin degradation prodcuts, D-dimer
- inhibitor consumption: antithrombin (AT)
What tests evaluate the different pathways of the coagulation cascade?
intrinsic = PTT/aPPT, ACT - (Poker Table Tournament INside)
extrinsic = PT - (Park Trucks OUTside)
What do the aPTT and ACT tests measure? What 2 things can a delayed time point toward?
measure time for fibrin clot formation
- deficiency or inhibitor of any intrinsic or common pathway factor
- heparin therapy
How does the aPTT test work? What is required for detection? How does it compare to the ACT?
measures time for fibrin clot formation in citrated plasma + contact activator + calcium + PLT phospholipid substitute
70% deficiency of any factor
more sensitive
What 3 things do prolonged aPTT results indicate?
- deficiency in intrinsic factors (12, 11, 9, 8)
- deficiency in common pathway factors
- increased concentration of inhibitors (heparin)
What does the ACT measure? How must samples be collected? What is required for detection?
time for fibrin clot formation in non-anticoagulated blood
specialized tube containing a contact activator and missing exogenous PLT phospholipids
95% deficiency of any intrinsic/common factor
What does PT measure? What is required for detection?
time for fibrin clot formation in citrated plasma + TF + calcium + PLT phospholipid substitute
70% deficiency of intrinsic factors
What 2 things do prolonged PT times indicate? Why is this a good screening test for vitamin K deficiency?
- deficiency of Factor VII
- deficiency or inhibition of common pathway factors (fibrinogen, thrombin, 5, 10)
short half-life of F7
What are 3 fibrinogen tests? What do they measure?
- heat precipitation - detects hypofibrinogenemia due to inflammation in large animals (not sensitive enough to detect hypofibrinogenemia)
- immunologic assays - detects amount, but not functionality of fibrinogen
- thrombin clotting time (TCT)/thrombin time (TT) - indicates amount of functional fibrin
What 3 things does a prolonged TCT or TT indicate? When are these tests done?
- hypofibrinogenemia
- dysfibrinogenemia
- presence of fibrinogen inhibitors
abnormal PT of PTT results
What is the PIKVA test? What is it used for?
proteins induced by vitamin K antagonist/absence
detects vitamin K deficiency by measurig inactive forms of Factors 2, 7, 9, 10
What causes the formation of fibrin degradation products and D-dimers?
fibrinogen and soluble fibrin are broken down by plasmin
cross-linked fibrin by plasmin
What is the latex agglutination test? What do excessively high results indicate?
uses latex beads coated with antibodies directed against FDPs or D-dimers —> agglutination = presence of FDPs or D-dimers
excessive fibrinolysis
It is rare to find only FDPs elevated in latex agglutination tests. When would this occur?
large cavitary bleeds (rodenticide, hemophilia) due to increased breakdown of fibrinogen
In what 3 situations are FDPs and D-dimers commonly increased? Which increased result is more sensitive and specific?
- increased fibrinolysis
- severe internal hemorrhage with fibrinolysis (DIC, thrombosis (ALWAYS seen in animals with late DIC)
- decreased clearance of FDP by liver
D-dimers
In what 3 situations is antithrombin commonly decreased?
- decreased production in liver failure
- increased loss (protein-losing nephropathy)
- increased consumption (DIC)
What 4 hemorrhage patterns are seen with coagulopathies?
MAJOR hemorrhages, often in multiple sites
- subcutaneous or intramuscular hematomas
- ecchymosis
- bleeding into cavities (hemothorax, hemoabdomen, joints)
- blood in stool, vomit, or urine
What is the most common cause of coagulopathies? What are 3 other causes?
decreased production of coagulation factors
- production of abnormal coagulation factors
- increased consumption or loss of factors
- presence of circulation inhibitors or antibodies directed against factors
How do deficiencies of certain factors effect clinical signs?
isolated deficiencies of certain factors, like 11 and 12, tend to be asymptomatic or cause mild bleeding problems, like bruising
F8 and F9 deficiencies or common pathway factors cause more severe problems
