9 - Coagulation Disorders Flashcards
Describe the Virchow triad in thrombosis
Thrombosis can be caused by 3 things:
- Endothelial injury (ex. car accident)
- Abnormal blood flow
- Hypercoagulability
When you expose ______ to blood it will induce clotting.
collagen
Describe the intrinsic pathway
-exposure of collagen basement membrane
-contact activation
F12 -> F12a
F11 -> F11a
F9 -> F9a + F8C
F10 -> F10a
Describe the extrinsic pathway
-tissue injury
-tissue thromboplastin (tissue factor)
F7 -> F7a
F10 -> F10a
Describe the common pathway
F10 -> F10a
(through F5a) F2 -> F2a
F2 = prothrombin
F2a = thrombin
F2a converts F1(fibrin) -> soluble fibrin
F2a is converted to F13, converted to F13a, which converts soluble fibrin to insoluble fibrin strands
In the presence of a clot, plasminogen is converted to _____
plasmin
Describe how vasoconstriction can cause a clot
- vasoconstriction endothelial adhesion
- stasis of blood flow
- platelets
- adhesion
- release reaction
- releases ADP, TXA2, Aggregation
- vWF
- platelet thrombus
- retracted fibrin thrombus “fibrin clot”
- soluble fibrin fragments (FDPs)
What is the only factor not generated by the liver?
Factor 8
*it is generated by endothelial wall
How does aspirin work?
inhibits COX enzymes
-platelets cannot regenerate and so it takes about a week to until new platelets are made
*in the blood vessel wall, COX is also inhibited which means PGI is inhibited.
PGI is prostacyclin which is a platelet anti-aggregator and vasodilator
**these can regenerate very quickly therefore will turn into PGI which is good bc it’s an anti-aggregator and vasodilator
What are examples of aDP receptor blockers?
clopidogrel, ticagrelor, prasugrel
What are some factors that predispose someone to bleeding?
- open vessel
- pro-clotting factor deficiencies
- platelet defects
In the absence of ______ we don’t clot
calcium
What is PT?
prothrombin time
What is INR?
international normalized ratio
What is PT or INR?
A test based on the time for detection of clot formation in a test tube of the patients’ plasma after the addition of thromboplastin and calcium.
Interpretation of PT/INR:
If it takes more than ___ seconds it is suggestive of a defective extrinsic and common pathway
12
INR test is sensitive to reductions in which factors?
2, 7, 10
What factors does warfarin reduce the synthesis of?
2, 7, 9, 10
Factor _ is very sensitive to warfarin
7
When administering warfarin, we need at least _____ hours for coverage of both pathways so we need to administer another agent.
48-72
The INR or PT is not altered by thrombocytopenia or defective platelets but it prolonged when the ______ level is low
fibrinogen
T or F: ASA or NSAID’s affect the INR
FALSE - they do not alter it
What is the antagonist for warfarin?
vitamin K
Out of factors 7, 9, 10, and 2, which has the shortest half life?
7
What is the formula for INR?
INR = {PT/PTc}^ISI
PT = patient's prothrombin time Pic = mean prothrombin time for your lab control ISI = international sensitivity index
What is the normal INR range?
0.9 - 1.1
White thrombi = _____ thrombi
arterial
Describe a white thrombi
Arterial thrombi - primarily made up of platelets but also fibrin and WBCs
Red thrombi = ______ thrombi
venous
Describe a red thrombi
Venous thrombi - primarily fibrin and RBC’s and a small platelet plug
ASA plays no role in the treatment of prevention of _______ thrombi
venous
White or Red:
Has more platelets (therefore can be treated and prevented with ASA)
White
Give some examples of procoagulants
- tissue thomboplastins
- exposed collagen
- activated factors
- thromboxane A2
- von Willebrand’s factor
- factor 8 coagulant material
Give some examples of anticoagulants
- Protein C & Protein S
- factor defiiencies
- antithrombin (AT)
- prostacyclin
- heparin
- tPA
- plasmin
Describe Type A Hemophilia
- deficiency of Factor 8-C
- normal Factor 8 - vWF
- “Classical Hemophilia”
Describe Type B Hemophilia
- deficiency of Factor 9
- “Christmas Disease”
Describe von Willebrand’s Disease
- diminished factor 8-vWF
- normal factor 8-C material
What is DIC?
Disseminated Intravascular Coagulation:
- simultaneous clotting & bleeding
- commonly seen with severe sepsis or postpartum women
Why does severe liver disease cause bleeding or clotting?
Because all factors (except 8) are made by the liver.
- Causes decreased synthesis of Factors 1-13 (except 8)
- DIC may also occur
- NOTE: there is also a decrease in synthesis of AT, plasminogen, and alpha 2-antiplasmin
THEY COULD EITHER BLEED OR CLOT
__________ = platelet count < 100,000
Thrombocytopenia
What could cause thrombocytopenia?
- a decrease in bone marrow production
- increased peripheral (i.e. circulating blood) destruction
What are a few known thrombogenic risk factors? (i.e. risk factors that would increase your risk for clotting)
- obesity
- age > 40
- malignancy
- immobilization
- major surgery
- AMI (acute MI)
- multiple trauma
What type of deficiency results in heparin not working?
anti thrombin 3
How does unfractionated heparin (UF) work?
binds with AT and neutralizes activated forms of factors 2, 9, 10, 11, 12