Hemostasis Flashcards
What are the 4 stages of hemostasis?
I: Primary
II: Secondary
III: Anticoagulation
IV: Fibrinolysis
What are the 4 main stages of primary hemostasis?
1) adhesion
2) activation
3) aggregation
4) fibrin
______ promotes platelet ADHESION.
von Willebrand factor (vIII)
Where is vWF manufactured and released from?
endothelial cells
vWF is the ligand for the _______ receptor found on the platelet.
GP1b
What is the life span of a PLT?
8-12 days
What is the normal value for PLT’s?
150,000-400,000 cells per mL
What percent of the PLT’s can be found sequestered in the spleen?
33%
What is the MOST common inherited coagulation defect?
vWF disease (vIII) *the more common form is characterized by insufficient production of vWF by endothelial cells
Why should you still suspect vWF disease in a pt with a normal PLT count and increased bleeding time?
they may have enough platelets, but it is the vWF that adheres the PLT to the injury site
What is the 1st line treatment for vWF disease? How does it work?
D-amino D-arginine vasopressin (DDAVP, desmopressin)–> a non pressor analogue of arginine vasopressin causes release of endogenous stores of vWF
effective in 80% of cases
What is the dosing for DDAVP for vWF?
0.3mcg/kg IV infusion for 10-20 minutes
PLT adhesion is increased within 30 minutes of injection and wears off at 4-6 hours
What is the concern with DDAVP administration in vWF disease type 2B?
thrombocytopenia
What is given to patients that do not respond to desmopressin for vWF disease?
cryoprecipitate or factor VIII concentrate (Humate-P)
What factors does cryoprecipitate have?
factor VIII, I (fibrinogen), XIII
What is needed to activate the PLT?
thrombin (activated factor II or IIa)
What is synthesized and released from the activated PLT?
thromboxane A2 and ADP
What is the role of thromboxane and ADP?
uncovers fibrinogen receptors on the platelet by conformational change—> it binds to the receptor activating signal transduction—> fibrinogen then attaches thereby linking other PLT’s to each other
What is formed during aggregation?
platelet plug
How strong is a PLT plug?
water soluble and friable
also called a white thrombus or white clot
_______ aggregates platelets.
fibrinogen (factor I)
What occurs in the PLT after the thrombin attaches?
it is activated–> phospholipase A2 liberates arachidonic acid–> cyclooxygenase converts arachidonic acid to prostaglandin G2–> PGG2 is metabolized to PGH2–> PGH2 is converted to a variety of prostaglandins and thromboxane A2
This is the arachidonic acid cascade.
Name the arachidonic acid cascade.
phospholipase A2 liberates arachidonic acid–> cyclooxygenase converts arachidonic acid to prostaglandin G2–> PGG2 is metabolized to PGH2–> PGH2 is converted to a variety of prostaglandins and thromboxane A2
What part of hemostasis does drugs like aspirin, NSAIDs, and Plavix effect?
platelet aggregation
What is the fibrinogen receptor?
GPIIb/IIIa
Name common anti-fibrinogen receptor drugs.
Eptifibatide (integrilin)
Abciximab (Reopro)
Tirofiban (Aggrastat)
Remember “EAT”
How many hours before surgery should the following drugs be discontinued?
Eptifibatide (integrilin)
Abciximab (Reopro)
Tirofiban (Aggrastat)
Eptifibatide (integrilin)–> 24 hours
Abciximab (Reopro)–> 72 hours
Tirofiban (Aggrastat)–> 24 hours
How many hours before surgery should the following drugs be discontinued?
Aspirin
NSAIDs
Aspirin: 7-10 days (life of PLT)
NSAID: 24-48 hours
How do the following drugs work?
Eptifibatide (integrilin)
Abciximab (Reopro)
Tirofiban (Aggrastat)
They cap the fibrinogen receptor to prevent attachment of fibrinogen–> so no aggregation
Name 2 anti ADP drugs.
Clopidogrel (Plavix)–> anti ADP agent (life of PLT)
Ticlopidine (Ticlid)–> inhibits ADP induced fibrinogen aggregation
How many hours before surgery should the following drugs be discontinued?
Clopidogrel (Plavix)
Ticlopidine (Ticlid)
Clopidogrel (Plavix)–> 7-10 days (life of PLT)
Ticlopidine (Ticlid)—> 14 days
How does the drug Dipyridamole (Persantine) work? What is it commonly used for?
increases cAMP in pt’s—> increased cAMP prevents aggregation of PLTs
commonly used in combination with warfarin to treat prosthetic heart valves
What is the MOST common ACQUIRED blood clotting defect?
inhibition of cyclooxygenase production by aspirin or NSAIDs
There is no factor ______.
VI
Where do platelets come from?
bone marrow–> thrombocytes
Secondary Hemostasis is all about the production of _____.
Fibrin
If it requires vitamin K it MUST be made in the ______.
liver
What are the vitamin K dependent factors?
II, VII, IX, X (procoagulants) and protein C & S (anticoagulants)
All procoagulant factors except _____, _______, and ______ are made in the liver.
vWF (VIII) made in endothelial cells, tissue factor (III) made in the tissues, and calcium (IV) from diet
______ is woven into platelets and crosslinked.
fibrin
How strong is a fibrin clot?
insoluble in water; stable
also called a red clot or red thrombus
Cross-linking of fibrin strands requires coagulation factor _______. The final steps in fibrin production involve the ________ pathway.
XIIIa (fibrin stabilizing factor)
extrinsic, intrinsic, and final common pathways
________ gets converted into fibrin and creates a _____ bond after being stabilized by XIIIa.
fibrinogen
covalent
*cryo contains I, VIII, XIII–> helps stabilize fibrin
What is the Leroy Brown story of the extrinsic, intrinsic, and final common pathways?
Look man, I picked up 0.37 cents outside (EXTRINSIC) and I really want those potato wedges… I can’t pay 12.00 but I can give you 11.98 (INTRINSIC)….. “No man”…. Look fool, It’s common on Friday the 13th to kill 1, 2, 5, 10 of you fools (COMMON)
What is the textbook answer for appropriate heparinization for cardiac surgery?
400-450
Warfarin (coumadin) interferes with the ______ pathway.
extrinsic
Prothrombin time (PT) and the International Normalized Ratio (INR) assess the _________ pathway.
extrinsic
Heparin interferes with the ________ pathway.
intrinsic
Partial thromboplastin time (PTT) and activated coagulation time (ACT) assess the ______ pathway.
intrinsic
What is the second MOST common INHERITED coagulation disorder?
hemophilia A
So both are factor VIII
1) vWF
2) VIII:C hemophilia factor
What is the difference in hemophilia A and hemophilia B?
hemophilia A is from factor VIII:C, hemophilia B is from christmas factor IX deficiency
What is the most important clue to clinically significant bleeding disorders in an otherwise healthy patient?
THE HISTORY
What is the most common reason for coagulopathy in patients receiving massive blood transfusions?
Lack of platelets
*PLT’s in stored blood are non functional after 1-2 days…. there is also dilution of factors V and VIII
What is the only acceptable clinical indication for transfusion of packed red blood cells?
to increase oxygen carrying capacity of blood
ALL procoagulants except ______ are present in fresh frozen plasma.
platelets
Cryoprecipitate contains factor _______, factor ______, and factor ______.
factor I (fibrinogen), factor VIII (both vWF and C), and factor XIII (fibrin stabilizing factor)
How is cryoprecipitate harvested?
from FFP as it is thawing
One unit of platelets will increase count by _______.
5,000-10,000/mm3
One unit of RBCs will increase Hct by ______% or ____g/dl.
3-4% or 1g/dl
1 cc/kg of RBCs will increase Hct by _____%.
1%
Massive transfusion is defined as ___________.
one complete blood volume transfused within 24 hours
What is the role of antithrombin?
it binds thrombin (factor IIa) and factor Xa GREATLY
it binds IX, XI, and XII to a LESSER extent
removes them from circulation–> anticoagulating the blood
How does heparin work?
increases the effectiveness of antithrombin 1,000 fold or more
Where is antithrombin made?
the liver
Heparin binds to _______.
antithrombin III
Heparin increases the rate of thrombin-antithrombin reaction by _______.
1000 fold or more
Name 2 disease processes that can cause an acquired antithrombin deficiency state.
1) cirrhosis of liver
2) nephrotic syndrome
What is the MOST common reason a patient can be unresponsive to heparin?
b\c they have an antithrombin deficiency
What is the appropriate ACT result indicating that a patient has been adequately heparinized before a CABG?
> 400s
if the ACT is low you can give FFP because FFP contains all coagulation and anticoagulation factors made by the liver–> including antithrombin
What pathway or pathways does heparin block?
classical intrinsic and final common pathway
What is the reversal for heparin?
protamine
How does protamine work to reverse heparin?
it is a positively charged substance that combines electrostatically with heparin, a negatively charged substance–> this is a neutralization reaction
Protamine reverses the action of heparin by ______.
neutralization
Warfarin (coumadin) binds to ______ receptors in the ______.
vitamin K receptors in the liver—> production of vit K dep factors (II, VII, IX, X) is depressed
What pathway is blocked with warfarin?
classical extrinsic and final common pathways
Recombinant hirudin, ximelagatran, and argatroban are direct _____ inhibitors.
thrombin
What two tests assess heparin?
PTT and ACT
Heparinization is adequate if the ACT is > _______ sec.
400-450 sec
What is the normal value? bleeding time
3-10min
What is the normal value? platelet
150-400,000 cells/ml
What is the normal value? prothrombin time (PT)
12-14 sec
What is the normal value? activated partial thromboplastin time (PTT)
25-35 sec
What is the normal value? activate coagulation time (ACT)
80-150sec
_______ is the body’s clot buster.
plasmin
How does plasminogen (inactivated form of plasmin) get converted into plasmin? (2)
tpa and upa
tissue type plasminogen activator
urokinase type plasminogen activator
When a clot is formed, what is there all along that will assist in the destruction of the clot at a later time?
plasminogen is incorporated into the clot as it is formed
Plasminogen, the inactive form of plasmin, is synthesized in the ________ and circulates in the blood.
liver
Where is TPA made and what is its role?
its made in endothelial cells—> released when needed to convert plasminogen into plasmin
Aprotinin and Amicar (epsilon aminocaproic acid) work by _______.
inhibiting plasmin
When plasmin is inhibited, fibrin that is formed breaks down _______, so bleeding is _______.
slowly; decreased
What is the definitive test for DIC?
none
Name some conditions that contribute to or cause DIC?
sepsis, hemolysis, transfusion reaction, ischemia, hypotension, obstetrical emergencies (abruptio placenta, amniotic fluid embolism), acute DIC in surgical patients
What are some causes of acute DIC in surgical patients?
infection, shock, and ischemia are MOST common precipitating factors of acute DIC in surgical patients
What lab abnormalities reflect consumption of clotting factors and enhanced fibrinolysis that can be seen with DIC?
decreased–> PLTs, fibrinogen, prothrombin, levels of factors V-VIII-XIII
increased–> fibrin degradation products
What is the most common cause of isolated high “PT”?
liver disease
What is the treatment for coagulation abnormalities associated with liver disease?
replace clotting factors with FFP, cryoprecipitate, and vit K as needed
Coagulation abnormalities can be associated with massive blood transfusion. What is deficient in transfused blood?
platelets, and factors V and VIII
Treatment: platelet transfusion, FFP (supplies all coagulation factors), cryoprecipitate is a primary source of factor I (fibrinogen), VIII, and XIII
What clotting factor is considered the physiologic initiator of the coagulation cascade?
III (tissue factor or thromboplastin)
Antithrombin III inhibits what 5 clotting factors?
II, IX, X, XI, XII
II and X MOST profoundly inhibited
How does protamine work to reverse heparin? What kind of reaction is this?
combines electrostatically; neutralization
Name 3 substances that convert plasminogen to plasmin.
1) tpa
2) upa
3) streptokinase
When is aprotinin generally used in anesthesia? How does it work?
for repeat sternotomies and works by inhibiting plasmin
What is the BEST test for primary hemostasis, or platelet function?
standardized skin bleeding time
What are the typical manifestations of DIC?
bleeding, with oozing from tubes, wounds, and vascular access sites
