Valley: Hemostasis Flashcards
What are the 4 steps involved in primary hemostasis?
- Adhesion of platelets to damages vascular wall
- Activation of platelets
- Aggregation of platelets
- Production of fibrin
Adhesion of platelets to damages vascular walls (requires ———, also known as factor —)
Von willebrand’s factor; 8
Activation of platelets (requires —, which is factor —)
Thrombin ; 2a
Aggregation of platelets (requires — and ——)
ADP and thromboxane A2
Production of fibrin (requires —, —, and ——— coagulation factors)
Extrinsic, intrinsic, and final common pathways
Platelets have an average life span of — to —days
8-12
Normal platelet count is — to — cells per ml
150,000 to 400,000
Approximately — of the platelet pool is sequestered in the spleen
33%
When vascular endothelium is damages and the subendothelium of the blood vessel wall is exposed, von willebrand’s factor anchors platelets to the — layer of the subendothelium.
Collagen
Von willebrand’s factor promotes — adhesion
Platelet
Von willebrand’s factor is manufactured, and released from, ——.
Endothelial cells
What is the most common inherited coagulation defect?
Von willebrand’s disease
—, a non-pressor analogue of arginine vasopressin, causes release of endogenous stores of vWF and is the first-line treatment for von willebrand’s disease
D-amino-d-arginine vasopressin (desmopressin, DDAVP)
When DDAVP is used with von willebrand’s disease, platelet adhesion is increased within — minutes of injection and wears off at — to — hours.
30 minutes; 4-6 hours
What is a side effect that occurs in children with the use of DDAVP?
Hyponatremia
DDAVP causes — in type 2B von willebrand’s disease.
Thrombocytopenia
— is the standard treatment for von willebrand’s disease.
DDAVP (desmopressin)
Von willebrand’s factor can be increase by giving what 3 things?
- Desmopressin (DDAVP)
- Cryoprecipitate
- Purified factor VIII
What 3 factors do cryoprecipitate contain?
- Factor VIII
- Factor 1 (fibrinogen)
- Factor XIII
Patients who do not respond to desmopressin with von willebrand’s disease should receive — or —.
Cryoprecipitate or factor VIII concentrate
What is treated to inactivate HIV and hepatitis viruses?
Pooled factor VIII concentrate
— combines with the thrombin receptor on the platelet surface to activate the platelet.
Thrombin (factor II)
Among the numerous mediators released from the activated platelets, what are the 2 that promote platelet aggregation?
- ADP
- Thromboxane A2
— activates the platelet.
Thrombin (factor II)
Thromboxane A2 and ADP uncover — receptors.
Fibrinogen
When fibrinogen attaches to its receptors, thereby linking platelets to each other the clot is still — and —.
Water-soluble and friable
— aggregates platelets.
Fibrinogen (factor I)
Cyclooxygenase (COX) is rendered non-functional because the — group of aspirin causes acetylation of cyclooxygenase.
Acetyl
— is the rate-limiting enzyme in the conversion of arachidonic acid to thromboxane A2.
Cyclooxygenase
When considering aspirin, without — then platelet aggregation is impaired.
Thromboxane A2
What are the 5 most common pharmacological causes of abnormal platelet aggregation?
- Aspirin
- NSAIDs
- Plavix (clopidogrel)
- Ticlopidine (Ticlid)
- Dipyridamole (Persantine)
What is the main difference with aspirin and NSAIDs?
NSAIDs depression of thromboxane A2 production by platelets is temporary (~24-48hrs), not permanent
Which antiplatelet drug is an anti-ADP agent (life-time of the platelets)
Plavix (clopidogrel)
Which antiplatelet drug inhibits ADP-induced fibrinogen aggregation of platelets?
Ticlopidine (ticlid)
How early should you discontinue Ticlopidine (ticlid)?
14 days before surgery
Which antiplatelet drug increases cAMP in platelets?
Dipyridamole (persantine)
cAMP prevents — of platelets
Aggregation
How early do you discontinue dipyridamole (persantine)?
24 hours before surgery
How do anti-fibrinogen receptor (GPIIb/IIIa) drugs work?
“cap” and block the fibrinogen receptor (GPIIb/IIIa), preventing attachment of fibrinogen resulting in no linking of platelets and no aggregation
How early should eptifibatide (integrilin) be discontinued?
24 hours before surgery
How early should abciximab (ReoPro) be discontinued?
72 hours before surgery
How early should tirofiban (aggrastat) be discontinued?
24 hours before surgery
— activates the platelet.
Thrombin
Aspirin — inhibits cyclooxygenase
Irreversibly
Aspirin inactivates the life time of the platelet, which is about — to — days.
8-12
NSAIDs — inhibit cyclooxygenase.
Reversibly
NSAIDs inhibit the platelet for — to — hours.
24-48 hours
The most common acquired blood clotting defect is due to inhibition of — production by aspirin or NSAIDs.
Cyclooxygenase
Which clotting factors are vitamin K dependent?
1972 ; 10,9,7,2
All procoagulant clotting factors are made in the liver except for which 3?
- Von willebrand’s factor (VIII;vWF)
- Tissue factor (factor 3)
- Calcium (factor 4)
Factor VIII:vWF regulates the production or release of factor —.
VIII:C
Which clotting factor is the source of vascular wall and extravascular cell membranes; released from traumatized cells?
Tissue factor or thromboplastin (factor 3)
Which clotting factor is the source of diet?
Calcium (factor 4)
Which clotting factor is the source of vascular endothelial cells?
Von willebrand’s factor (factor VIII:vWF)
What 2 proteins are vitamin K dependent?
Protein C and protein S
After — aggregate, — is woven into platelets and cross-linked.
Platelets; fibrin
Cross-linked fibrin is — in water.
Insoluble
Cross-linking of fibrin strands requires coagulation factor —.
13
What 2 factors are included with the extrinsic pathway?
7 and 3
Damage outside of blood vessels triggers the release of — (factor —) from damaged cells.
Thromboplastin (factor 3, tissue factor)
Thromboplastin activates factor —.
7
Activated factor 7 activates factor —.
10
What 4 factors are involved with intrinsic pathway?
12, 11, 9, 8
What 4 factors are involved in the common pathway?
10, 5, 2, 1
What is needed for fibrin to start cross-linking?
Factor 13
Coumadin acts on the — and — pathways.
Extrinsic and final common
Coumadin is assessed by — and — blood tests.
PT and INR
Heparin acts on the — and — pathways.
Intrinsic and final common
Heparin is assessed by — and — blood tests.
PTT and ACT
The — pathway is initiated in response to damage occurring outside the blood vessel.
extrinsic
The coagulation factors of the extrinsic pathway are — and —.
III (also known as tissue factor or thromboplastin) and VII
The — pathway is initiated by damage inside the blood vessel.
intrinsic
The coagulation factors of the intrinsic pathway are —, —, —, and —.
XII, XI, IX, and VIII
The coagulation factors of the final common pathway are —, —, —, —, and —.
X, V, II, I and XIII
For 37 cents you can purchase the — pathway.
extrinsic
If you cannot buy the — pathway for $12, you can get it for $11.98.
intrinsic
The — pathway can be purchased at the five (V) and dime (X) for 1 (I) or 2 (II) dollars on the 13th (XIII) of the month.
final common
Fibrin cross-linking occurs in the presence of factor —.
XIII
Warfarin (Coumadin) interferes with the — pathway.
Extrinsic
Prothrombin time (PT) and 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
Most common inherited bleeding disorder?
Von willebrand’s disease
Sex-linked recessive genetic disorder that is carried by the female member of a kindred and affects males almost exclusively and the second most commonly inherited coagulation disorder (occurs in 1 of 10,000 male births)
Hemophilia A (factor VIII:C deficiency)
3 treatment options for hemophilia A?
Fresh frozen plasma (FFP), cryoprecipitate, and factor 8 concentrate
Christmas disease; factor 9 deficiency
Hemophilia B
The most important clue to clinically significant bleeding disorder in an otherwise healthy patient
remains the —.
history
The most common reason for coagulopathy in patients receiving massive blood transfusions is the lack of functioning —.
platelets
Platelets in stored blood are nonfunctional after —to— days.
1-2 days
Abnormalities of coagulation owing to dilution of factors — and — may also occur, especially if packed red blood cells are infused with a minimal volume of plasma.
V and VIII
The only acceptable clinical indication for transfusion of packed red blood cells is to increase the ——— of the blood.
oxygen carrying capacity
All procoagulants except — are present in fresh frozen plasma (FFP).
platelets
Cryoprecipitate contains factor —, factor —, and factor —.
factor VIII, factor I, and factor XIII.
— is harvested from fresh frozen plasma as it is thawing.
cryoprecipitate
One unit of RBCs will increase hematocrit (Hct) —%, or —/dL.
3-4%, or 19/dL.
1 cc/kg RBCs will increase Hct —%.
1
One unit of platelets will increase platelet count — - —/mm3.
5,OOO-lO,000
“Massive transfusion” is defined as 1 complete blood volume transfused within — hours.
24
Activated antithrombin binds factor — and factor — greatly and factors —, —, and — to a lesser degree.
thrombin (factor IIa) and factor Xa greater ; factors IX, Xl, and XII lesser
— works by increasing the effectiveness of antithrombin 1,000-fold or more
Heparin
Antithrombin is made in the — and neutralizes — pathway factors and — pathway factors by forming complexes with them
liver ; final common pathway factors and intrinsic pathway factors
— is a required cofactor for heparin
Antithrombin
Heparin binds to —
antithrombin III
Acquired antithrombin deficiency states are found in patients with what 2 issues?
Cirrhosis of the liver and Nephrotic syndrome
An antithrombin deficiency is the most common reason a patient is unresponsive to —.
heparin
A patient scheduled for CABG surgery is heparinized. The ACT is reported to be 210 seconds. After administration of more heparin, the ACT is 240 seconds. Is the patient adequately heparinized? What should you do?
Patient is not adequately heparinized. ACT should be greater than 400 seconds. Give the patient fresh frozen plasma (FFP). FFP contains all coagulation and anticoagulation factors made by the liver, including antithrombin. Then proceed with the case.
— forms a complex with antithrombin III.
Heparin
The — is prolonged by heparin. Heparin blocks the classical — and — pathways.
partial thromboplastin time (PTT) ; intrinsic and final common pathways
Protamine reverses the action of heparin by —.
neutralization
Warfarin (Coumadin) and other coumarin-like substances bind to the — receptor in the liver and competitively inhibit —.
vitamin K ; vitamin K
— is prolonged by warfarin. Warfarin and other coumarins block the classical — and — pathways.
Prothrombin time (PT) ; extrinsic (factor VII) and final common (factors II and X) pathways
Reombinant hirudin, ximelagatran, and argatroban are — inhibitors.
direct thrombin
Normal value for bleeding time?
3-10min
Normal value for platelet count?
150,000-400,000 cells/mL
Normal value for prothrombin time (PT)?
12-14 sec
Normal value for partial thromboplastin time (PTT)?
25-35 sec
Normal value for thrombin time (TT)?
<30 sec
Normal value for activate coagulation time (ACT)?
80-150 sec
Normal value for fibrinogen?
> 150 mg/dl
— and — assess heparin
PTT and ACT
Heparinization is adequate if ACT — - — sec
> 400-450 sec
—, the inactive form of plasmin, is synthesized in the liver, circulates in the blood, and is incorporated into a clot as the clot is formed.
Plasminogen
— and — are the two agents that normally convert plasminogen to its active form, plasmin.
Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA)
Plasmin breaks down —.
fibrin
— is synthesized in the liver and circulates in the blood
Plasminogen
-incorporated with fibrin in the forming clot
-produced by endothelial cells and released into the circulation
-release is stimulated by thrombin and venous stasis
-by binding avidly to fibrin, converts plasminogen to plasmin within the thrombus
Tissue-type plasminogen activator (tPA)
-found in limited amounts in the blood
-has little affinity for fibrin
-most widely used thrombolytic agent for intra-arterial infusion into the peripheral arterial system and grafts
Urokinase-type plasminogen activator (uPA)
-produced by beta-hemolytic streptococci
-has little affinity for fibrin
-preformed antibodies to this may inactivate it
Streptokinase
What are the 3 plasminogen activators?
Tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and streptokinase
Aprotinin (Trasylol) inhibits —.
plasmin
Epsilon aminocaproic acid (Arnicar, EACA) and tranexamic acid prevent the breakdown of — by preventing displacing the plasmin.
fibrin
Aprotinin and amicar work by inhibiting —.
plasmin
What is the one increased laboratory abnormality of clotting factors and enhanced fibrinolysis of DIC?
Fibrin degradation products
— is the “Most common cause of an isolated high PT”
Liver disease
Treatment for coagulation abnormalities with liver disease?
Replace clotting factors with fresh frozen plasma, cryoprecipitate, and vitamin K as needed
Treatment for coagulation abnormalities with renal failure?
Adequate dialysis and elevation of hematocrit, cryoprecipitate, and DDAVP
Transfused blood is deficient in — and coagulation factors — and —
platelets ; V and VIII
Diffuse bleeding during massive transfusion is generally caused by —.
thrombocytopenia
Treatment for coagulation abnormalities with massive blood transfusion?
Platelet transfusion (correct thrombocytopenia), fresh frozen plasma (supplies all coagulation factors), cryoprecipitate (source of factor I, VIII, and XIII)
When the endothelial lining of the blood vessel is damaged, platelets adhere to the subendothelial collagen. What substance anchors platelets to subendothelial collagen?
Von Willebrand’s factor (VlII:vWF or VIII:R)
What clotting factor activates the platelet at the site of vascular injury?
thrombin (factor lIa)
What two substances, released from the activated platelet, stimulate platelet aggregation?
ADP and thromboxane A2
What substance links platelets together (aggregates them)?
fibrinogen (factor I)
What agents inhibit platelet aggregation by impairing cyclo-oxygenase?
aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs)
What clotting factors are found in the extrinsic pathway?
III (also known as tissue factor or thromboplastin) and VII
What clotting factors are found in the intrinsic pathway?
XII, XI, IX, and VIII
What clotting factors are found in the final common pathway?
I, II, V, X, XIlI
What clotting factor is considered the physiologic initiator of the coagulation cascade?
III (also known as tissue factor or thromboplastin)
What clotting factor promotes fibrin cross-linking?
XIII
Antithrombin III inhibits what five clotting factors? Which of these five is in the intrinsic pathway? What two of these five clotting factors are most profoundly inhibited?
II, IX, X, XI, and XII (IX, XI and XII are in the intrinsic pathway; II and X are most profoundly inhibited)
What four clotting factors are vitamin K dependent? Which of these is in the extrinsic pathway?
II, VII, IX, and X (VII is in the extrinsic pathway)
How does heparin work?
heparin increases the activity of (“turns on”) antithrombin III
How does coumadin work?
coumadin competitively inhibits the vitamin K- dependent clotting factors
What anticoagulant affects the extrinsic and final common pathways?
warfarin (coumadin)
What anticoagulant affects the intrinsic and final common pathways?
heparin
What two coagulation tests assess the extrinsic pathway?
prothrombin time (PT) and the international normalized ratio (INR)
What two coagulation tests assess the intrinsic pathway?
partial thromboplastin time (PTT) and activated coagulation time (ACT)
How does protamine work to reverse heparin? What kind of reaction is this?
protamine combines electrostatically with heparin (this is a neutralization reaction)
What enzyme is responsible for breaking down fibrin?
plasmin
What two pharmacological agents inhibit plasmin?
epsilon-aminocaproic acid (Amicar) and aprotinin (Trasylol)
Name three substances that convert plasminogen to plasmin?
urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and streptokinase
When is aprotinin generally used in anesthesia? How does it work?
aprotinin is used for repeat sternotomies and works by inhibiting plasmin
What is the normal activated coagulation time?
80-150 seconds
What is the best test of primary hemostasis, or platelet function?
standardized skin bleeding time
What is the most common reason for coagulopathy after a massive blood transfusion?
lack of functioning platelets (thrombocytopenia)
What clotting factors are found in fresh frozen plasma?
all procoagulants
Cryoprecipitate contains what clotting factors?
factor I (fibrinogen), factor VIII, and factor XIIl
What are the typical manifestations of disseminated intravascular coagulopathy?
bleeding, with oozing from tubes, wounds, and vascular access sites
Transfused blood is deficient in what two coagulation factors?
factors V and VIII
What is the most common inherited coagulation defect?
Von Willebrand’s disease
The patient with von Willebrand’s disease has not responded to desmopressin (DDAVP). What will
you try next?
a. Fresh frozen plasma
b. Cryoprecipitate
c. Amicar
d. Plasmin
Cryoprecipitate
What antiplatelet agent prevents ADP-induced platelet aggregation?
a. Aspirin
b. Ibuprofen
c. Ketorolac
d. Ticlopidine
Ticlopidine
Each of the following clotting factors is made in the liver EXCEPT:
a. VIII:C.
b. IV.
c. X.
d. XII.
IV
The clotting factor that is responsible for cross-linking fibrin is
a. I.
b. II.
c. VII.
d. XIII.
XIII
What anticoagulant works on the extrinsic pathway, and what test assesses the effectiveness of this
anticoagulant? Anticoagulant&Test
a. Coumadin PT
b. Coumadin PTT
c. Heparin PT
d. Heparin PTT
Coumadin PT
Cryoprecipitate contains coagulation factors
a. I, VIII, XIII.
b. II, VII, X.
c. I, VII, X.
d. II, X, XI.
I, VIII, XIII.
When antithrombin III is activated by heparin, antithrombin III
a. releases factors I, III, VII, and XIII.
b. binds factors I, VII, and XIII.
c. releases factors II, IX, X, Xl, and XII.
d. binds factors II, IX, X, Xl, and XII.
binds factors II, IX, X, Xl, and XII.
A patient who is scheduled for CABG surgery is heparinized, and the ACT is less than 300 seconds.
The result is the same after a second dose of heparin. Why is the patient unresponsive to heparin, and what is your next action?
Reason for unresponsiveness to heparin&Next Action
a. Deficiency of plasmin ; Give FFP
b. Deficiency of plasmin ; Cancel case
c. Deficiency of antithrombin III ; Give FFP
d. Deficiency of antithrombin III ; Cancel case
Deficiency of antithrombin III ; Give FFP
Prothrombin time normally is
a. 3-5 seconds.
b. 12-14 seconds.
c. 25-35 seconds.
d. 80-150 seconds.
12-14 seconds.
The reaction of protamine with heparin is a
a. neutralization reaction.
b. covalent reaction.
c. hydrogen bonding reaction.
d. counterbalanced reaction.
neutralization reaction.
What substance converts fibrin to fibrin split products?
a. Tissue plasminogen activator
b. Amicar
c. Plasmin
d. Streptokinase
Plasmin
Each of the following statements about aprotinin is true EXCEPT:
a. Aprotinin may cause an allergic reaction when administered to a patient for the first time.
b. Aprotinin may cause an anaphylactic reaction if administered to a patient for the second time.
c. Aprotinin is indicated for patients who are undergoing a sternotomy for the second time.
d. Aprotinin accelerates the breakdown of fibrin.
Aprotinin accelerates the breakdown of fibrin.
Postoperative bleeding with continued oozing from wounds and catheter sites suggests what disorder?
a. Von Willebrand’s disease
b. Hemophilia A
c. Disseminated intravascular coagulopathy
d. Antithrombin III deficiency
Disseminated intravascular coagulopathy
Each of the following is decreased in the patient with disseminated intravascular coagulopathy EXCEPT:
a. fibrin split products.
b. fibrinogen.
c. prothrombin.
d. factor VIII.
fibrin split products.
What is the major cause of diffuse bleeding after a massive blood transfusion?
a. Antithrombin III deficiency
b. Thrombocytopenia
c. Factors V and VIII deficiency
d. Vitamin K deficiency
Thrombocytopenia
