Coagulation Flashcards
What are the four steps of hemostasis?
- Vasospasm
- Primary hemostasis (platelet plug)
- Secondary hemostasis (creation of factors for fibrin mesh)
- Fibrinolysis
Where are platelets produced?
By megakaryocytes in the bone marrow
How many platelets can the spleen sequester?
Up to 1/3!
In the absence of vascular injury, the endothelium inhibits platelet function by secreting:
Prostaglandin I2 (inhibits vWF adherence)
AND
Nitric Oxide (inhibits TXA2 receptors)
When a platelet degranulates, what does it release?
What are the five receptors on platelet membranes?
Activated platelets express two glycoproteins on their surface:
GpIIb
GpIIIa
The primary purpose of the coagulation cascade is to produce:
Fibrin
The intrinsic pathway is measured by which lab??
“It’s longer, so it’s measured by the PTT”
The extrinsic pathway is measured by which lab?
“It’s shorter, so it’s measured by the PT”
What are the vitamin K dependent factors
2
7
9
10
What is the first factor activated in the extrinsic pathway?
Factor 3: Tissue factor
Which medication inhibits the extrinsic pathway?
Warfarin
What are the three steps of the extrinsic pathway?
which factor has the shortest half life?
factor 7 @ 4-6 hrs
In patients with liver disease, this will be the first one impacted
There are four intrinsic pathway factors:
8, 9, 11, 12
The intrinsic pathway is activated by:
blood trauma
Which medication inhibits the intrinsic pathway?
Heparin
What are the five steps of the intrinsic pathway?
A deficiency of what factor causes Hemophilia A?
Factor 8
How long does it take to form a clot via intrinsic action?
About 6 minutes
The primary goal of both the intrinsic and extrinsic pathways is to produce ________ in order to make fibrin
prothrombin activator
The final common pathway begins where:
prothrombin activator (created by Xa and Factor 5) converts prothrombin (2) into thrombin (2a)
What does thrombin do?
It changes fibrinogen into fibrin (a monomer)
What is plasminogen?
A pro-enzyme synthesized in the liver that, when activated to plasmin, breaks down fibrin into fibrin degradation products
Where is plasminogen found?
Its actually built into the clot! It remains dormant until it’s activated
How is a clot broken down naturally?
The injured tissue slowly releases tPA over several days
What does tPA stand for?
Tissue Plasminogen Activator
What are the stages of the contemporary theory of coagulation?
What is a normal aPTT?
25-35 seconds
What pathways does aPTT measure?
intrinsic and final common pathways
What medications does aPTT measure?
Heparin, but not LMWH
Factors must be reduced by ____% in order for the aPTT to be affected
30%
Which pathways does PT assess?
Extrinsic and final common pathways
What is a normal PT?
12-14 seconds
Why is a normal aPTT longer than a normal PT?
Because the intrinsic pathway takes longer than the extrinsic pathway
Factors must be reduced by ____% in order for the PT to be affected
30%
What is INR?
A ratio that standardized PT
What is a normal INR?
about 1x control
What is a therapeutic INR on Warfarin?
2-3x control
What is ACT?
The activated clotting time, which is more accurate than aPTT when large doses of heparin are administered
What platelet count signifies risk of spontaneous bleeding?
<20,000
What platelet count signifies increased surgical bleeding risk?
< 50,000
What does D Dimer measures?
Fibrin degradation products
What is a normal D-Dimer?
<500
What is the MOA of heparin?
Binds to Antithrombin and increases its activity 1000x
The heparin-AT complex neutralizes:
9a
10a
11a
12a
Inhibits platelet function
What is the standard heparin dose for CPB?
300-400 units/kg
The risk of protamine allergy is highest in which people?
Fish allergy
Using NPH insulin
Vasectomy
Does heparin cross the placenta?
No
Why does protamine cause pHTN?
Thromboxane A2 and serotonin release
Why does protamine cause hypotension
increased histamine release
Where is endogenous heparin produced?
Liver, basophils, mast cells
Warfarin inhibits which factors?
All of the Vit K dependent ones:
2
7
9
10
In order for Vit K supplementation to work, what pathology must be absent?
Liver disease. If their liver doesn’t work anyway Vit K won’t help
Is warfarin protein bound?
Yes, highly
What are the risk factors for Vit K deficiency?
What is the drug name for exogenous Vit K?
Phytonadione
How long does it take to restore clotting factors with Vit K administration?
4-8 hours
How is Vitamin K administered?
Preferably oral. The IV form has a high risk of anaphylaxis and has to be given very slowly
There are three classes of antiplatelet drugs:
ADP receptor antag.
GPIIb/IIIa antagonists
COX inhibitors
Where do we obtain inactive Vit K?
Diet
Production by bacteria in the gut
List the ADP receptor inhibitors
Clopidogrel
Ticlopidine
Ticagrelor
List the GpIIb/IIIa antagonists
The “Ab Fibs”
Abciximab
Eptifibatide
Tirofiban
List the non-specific COX inhibitors
Aspirin and NSAiDS
List the COX-2 specific inhibitors
Celecoxib
Rofecoxib
There are four classes of anticoagulants:
Heparins
Thrombin Inhibitors
Factor X inhibitors
Vit K antagonists
List the thrombin inhibitors
Bivalirudin
Argatroban
What is the MOA of Aminocaproic acid?
Plasminogen activator inhibitor
What is the MOA of TXA?
Plasminogen activator inhibitor
What is the MOA of desmopressin?
Stimulates Factor 8 and vWF release
What is the most common inherited platelet disorder?
von Willebrand disease
What lab abnormalities are seen with vWD?
Increased pTT and bleeding time
Von Willebrand factor has two functions:
It serves as an anchoring point for platelets in exposed tissue AND it carries inactivated factor 8 in the blood stream
Hemophilia A is factor ______ deficiency
8
Hemophilia A is most common in males or females?
Males
Which is more severe: hemophilia A or Hemophilia B
Hemophilia A
What is the treatment for hemophilia A?
Factor 8 concentrate
FFP
Cryo
DDAVP
Hemophilia B is factor _____ deficiency
9
What is the treatment for Hemophilia B?
factor 9 concentrate has more side effects and is trickier to use than factor 8
________ is a treatment option for both Hemophilia A & B
Recombinant Factor 7
What are the risks of rFactor7?
A clot somewhere unfortunate:
MI
Embolic Stroke
PE
DVT
Which conditions have the highest risk of causing DIC?
Sepsis
Obstetric Complications
Malignancy
What considerations must be made for patients with antithrombin deficiency?
They won’t respond to heparin, because there’s no antithrombin to activate
Protein C and S work as a team to inhibit:
Factor 5
Factor 8
Factor V Leiden causes:
Resistance to the anticoagulant effects of protein c
What are the triggers for sickle cell crisis?
Pain
Hypothermia
Dehydration
Acidosis
What is the most common manifestation of sickle cell disease?
Vaso-Occlusive Crisis
Impaired tissue perfusion leads to ischemia
________ reduces the frequency of vaso-occlusive crises
Hydroxyurea
What is acute chest syndrome?
Dyspnea and pulmonary edema
What perioperative factors precipitate acute chest syndrome in sickle cell patients?
Hypoventilation
Narcotics
Splinting
Pain
What is a sequestration crisis?
The spleen removes sickled cells from the body faster than they can be produced in the marrow, leading to severe anemia
What is an aplastic crisis?
Because the life span of HgbS is so short, even a mild reduction in bone marrow activity can cause severe anemia. Usually precipitated by a viral infection
Factor 1 Name and Site of Synthesis
Fibrinogen
LIVER
Factor 2 Name and Site of Synthesis
Prothrombin
LIVER
Factor 3 Name and Site of Synthesis
Tissue Factor
VESSEL WALL
Factor 4 Name and Site of Synthesis
CALCIUM
Dietary
Factor 8 Name and Site of Synthesis
Antihemophilic
LIVER
Factor 9 Name and Site of Synthesis
Christmas Factor
LIVER
Factor 10 Name and Site of Synthesis
Stuart-Prower
LIVER
Xa combines with calcium and Factor 5 to form prothrombinase, which converts prothrombin into thrombin
Factor 11 Name and Site of Synthesis
Plasma thromboplastin antecedent
Factor 12 Name and Site of Synthesis
Hageman Factor
LIVER
Factor 13 Name and Site of Synthesis
Fibrin stabilizing factor
LIVER
