Hematology CH 38 Flashcards
The intima (inner layer- Endothelial) has a role in modulating
Procoagulants (Hemostasis)
Anticoagulants
Fribrinolytics
What is an important function of the endothelial lining of blood vessels
They repel blood components away from the vessel was to prevent activation of clotting mechanism
What does the Media (2nd layer - Subendothelial) contain?
It is extremely thrombogenic and very active, contains collagen and fibronectin
Collagen - important in PLT attachment
Fibronectin - Aids with aching fibrin during plug formation
Where is NO and Prostacyclin made and what is their role?
Produced by Endothelial (inner layer) cells, and influence Adventitia (Outer layer - Externa)
They work by causing vasodilation and increasing the flow of blood, therefore interfere with PLT formation and aggregation; limit procoagulant mediations “wash them away”
NO –> Muscle relaxation
Prostacyclin –> Lipid molecule
NO specific affects PLT function, by inhibiting?
adhesion
aggregation
binding (btw fibrinogen + GPllb/llla)
What role does the adventitia (externa - outer layer) play?
Participates in control of blood flow by influencing vessel’s DEGREE OF CONTRACTION
Where are PLTs formed and stored?
Formed in bone marrow
1/3rd stored in Spleen
(megakaryoctes are precursors for PLTs)
PLTs contain a nucleus, T/F?
False! They do not contain a nucleus, DNA, nor RNA. So they do not reproduce.
THEY DO contain mitochondria in cytoplasm, so they participate in aerobic & anerobic metabolism
PLTs store a large amount of
A) Mg
B) Ca
C) K
D) Na
B) Calcium
AND… various enzymes like vWF, Fibrinogen, PLT Factor 4, PLT growth Factor
PLTs produce
A) ADP
B) Prostacyclin
C) Vit K
D) Thrombin
D) Thrombin. Role of thrombin is to activate some coagulation factors and influence recruitment of PLT to injury site
When vessel wall injury occurs, what happens next?
Immediately contracts to cause tamponade and decrease blood flow to decrease bleeding
What mediates contraction (vasoconstriction)?
A) ADP & Thromboxane A2
B) Gpllb/llla & Fibrinogen
C) vWF & Gplb
D) None of the above
A) ADP & Thromboxane A2
Contraction results from ANS reflexes and expression of f the aforementioned
What are the 3 steps to form a primary plug?
Adhesion
Activation
Aggregation
What happens during adhesion? (Select all that apply)
A) ADP & Thromboxane A2 vasoconstrict
B) TF influences PLT activation
C) GPlb & Fibrinogen bind to form a plug
D) Gpllb/llla & vWF attach to attract PLTs; make them “sticky”
E) none of the above
D) Gpllb/llla & vWF attach to attract PLTs; make them “sticky”
What happens during Activation? (select all that apply)
What happens during adhesion?
A) ADP & Thromboxane A2 vasoconstrict
B) TF influences PLT activation
C) GPlb & Fibrinogen bind to form a plug
D) Gpllb/llla & vWF attach to attract PLTs; make them “sticky”
E) none of the above
B & D
TF will influence PLTs to undergo transformation and become activated, GPllb/llla will project off these PLTs and attach to Fibrinogen to help form primary plug
What happens during aggregation?
A) ADP & Thromboxane A2 vasoconstrict
B) TF influences PLT activation
C) GPlb & Fibrinogen bind to form a plug
D) Gpllb/llla & vWF attach to attract PLTs; make them “sticky”
E) none of the above
E.
During this time PLT releases alpha & dense granules, contractile granules, thrombin, and other important procoagulant activators as mediators responsible for PLT aggregation. Here the primary plug is solidified.
Small injuries primary plug is sufficient
Large injuries require secondary plug
What pathway influences the start of extrinsic pathway?
A) contact activation pathway
B) common pathway
C) TF pathway
D) intrinsic pathway
C) TF pathway
what pathway influences the start of intrinsic pathway?
A) contact activation pathway
B) common pathway
C) TF pathway
D) extrinsic pathway
A) contact activation pathway
What factors are in the intrinsic pathway?
A) 3, 7
B) 2, 7, 9, 10
C) 10, 5, 2, 1
D) 11, 12, 9, 8
D) 11, 12, 9, 8
What factors are in the extrinsic pathway?
A) 3, 7
B) 2, 7, 9, 10
C) 10, 5, 2, 1
D) 11, 12, 9, 8
A) 3, 7
What factors are dependent on vitamin K?
A) 3, 7
B) 2, 7, 9, 10
C) 10, 5, 2, 1
D) 11, 12, 9, 8
B) 2, 7, 9, 10
What factors are in the common pathway?
A) 3, 7
B) 2, 7, 9, 10
C) 10, 5, 2, 1
D) 11, 12, 9, 8
C) 10, 5, 2, 1
Note: Factor 13 (stabilizing fibrin) is like the “step-sister” is it what helps create that cross-link fibrin mesh
What factor is involved throughout common pathway to help activate?
A) 3
B) 7
C) 10
D) 4
Factor 4 which is Calcium
What is the name of Factor 1? (describe action)
A) Antihempohiliac
B) Christmas
C) Calcium
D) Fibrinogen
D) Fibrinogen
Action - Form a clot
What is the name of Factor 2? (describe action)
A) Proaccelerin
B) Prothrombin
C) Stuart prower
D) Fibrinogen
B
Action - when IIa, activates I, V, VIII, IX, Xlll, PLTs, & Protein C
What is the name of Factor 3? (describe action)
A) Prothrombin
B) Christmas
C) Thromboplastin
D) Plasma thromboplastin antecedent
C
Action - Cofactor of VII
What is the name of Factor 4? (describe action)
A) Antihempohiliac
B) Christmas
C) Calcium
D) Fibrinogen
C
Action - Promotes clotting reactions
What is the name of Factor 5? (describe action)
A) Proaccelerin
B) Proconvertin
C) Christmas
D) Fibrin stabilizing
A
Action - Cofactor of X, forms prothrombinase complex
What is the name of Factor 6? (describe action)
A) Antihempohiliac
B) Christmas
C) Calcium
D) Unassigned
D
Action - NONE
What is the name of Factor 7? (describe action)
A) Antihempohiliac
B) Proconvertin
C) Calcium
D) Fibrinogen
B
Action - Activates IX & X
What is the name of Factor 8? (describe action)
A) Antihempohiliac
B) TF
C) Calcium
D) Fibrinogen
A
Action - Cofactor to IX
What is the name of Factor 9? (describe action)
A) Thromboplastin
B) Proconvertin
C) Christmas
D) Stuart Prower
C
Action - Activates X
What is the name of Factor 10? (describe action)
A) Antihempohiliac
B) Proconvertin
C) Stuart Prower
D) Fibrinogen
C
Action - Activates II, forms prothrombinase complex with V
What is the name of Factor 11? (describe action)
A) Prothrombin
B) Christmas
C) Thromboplastin
D) Plasma thromboplastin antecedent
D
Action - Activates IX
What is the name of Factor 12? (describe action)
A) Hageman
B) Christmas
C) Thromboplastin
D) Plasma thromboplastin antecedent
A
Action - Activates XI
What is the name of Factor 13? (describe action)
A) Prothrombin
B) Fibrin stabilizing
C) Thromboplastin
D) Plasma thromboplastin antecedent
B
Action - cross-links fibrin
What is the name of vWF Factor? (describe action)
A) Prothrombin
B) Christmas
C) Thromboplastin
D) Von Willebrand
D
Action - Mediates adhesion
Which 3 factors are NOT synthesized by liver?
III - synthesized by vascular wall and extravascular cell membranes; released from traumatized cells
IV - comes from out diet
vWF - Synthesized in Endothelial cells
What is the name of Prekallikrein Factor? (describe action)
A) Christmas
B) Stuart Prower
C) Fletcher
D) Von Willebrand
C
Action - Activates XII, cleaves HMWK
What is the name of High MW Kininogen (HMWK) Factor? (describe action)
A) Tissue Factor
B) Contact activation factor
C) Fletcher
D) Von Willebrand
B
Action - Supports activation of prekallikrein, XII, XI
Which mediators vasoconstriction? (select all that apply)
A) ADP
B) tPA
C) Serotonin
D) NO
E) Protein C & S
F) Thromboxane A2
G) Urokinase
H) AT III
I) Plasminogen
J) Prostacyclin
A, C, F
Which mediators vasodilate? (select all that apply)
A) ADP
B) tPA
C) Serotonin
D) NO
E) Protein C & S
F) Thromboxane A2
G) Urokinase
H) AT III
I) Plasminogen
J) Prostacyclin
D, J
Which mediators have fibrinolytic properties? (select all that apply)
A) ADP
B) tPA
C) Serotonin
D) NO
E) Protein C & S
F) Thromboxane A2
G) Urokinase
H) AT III
I) Plasminogen
J) Prostacyclin
B, G, I
Which mediators have anticoagulant properties? (select all that apply)
A) TF pathway inhibitor
B) vWF
C) Serotonin
D) Fibronectin
E) Protein C & S
F) Collagen
G) Urokinase
H) AT III
I) Plasminogen
J) Thrombomodulin
A, E, H
TF inhibitor prevents TF from working
Protein C & S degrade 5 and 8
AT lll degrades 12, 11, 9, 10, 2
Which mediators have procoagulant properties? (select all that apply)
A) TF
B) vWF
C) Serotonin
D) Fibronectin
E) Protein C & S
F) Collagen
G) Urokinase
H) AT III
I) Plasminogen
J) Thrombomodulin
A,B, D, F, J
TF is a coagulant factor
Collagen - tensile strength
vWF - adhesion
Fibronectin - mediates cell adhesion
Thrombomodulin - regulates anticoagulant pathway
What are 2 antifibrinolytic drugs used to combat clot degradation?
Aminocaproic acid
Tranexamic acid
Is Vit K a procoagulant or anticoagulant?
Procoagulant
Which is the site where the intrinsic and extrinsic converge?
A) V
B) X
C) Va
D) II
E) Xa
F) lla
E) Xa
Which factor is first depleted (dt short half life) of all VIT K dependent factors?
A) 2
B) 7
C) 9
D) 10
B) 7
Tx: Vit K 10-20mg IM
Thrombin (Factor lla) assists in activating which factors?
A) 3, 7
B) 2, 7, 9, 10
C) 1, 5, 8, 13
D) 10, 5, 2, 1
E) 11, 12, 9, 8
C) 1, 5, 8, 13
And, it influences recruitment of PLTs to sire of injury.
Thrombin can also behave as an anticoagulant
In what 3 ways does thrombin behave as an anticoagulant? (select 3)
A) Activates l
B) Releases tPA
C) Binds with vWF
D) Simulates Gpllb/llla
E) Binds with AT3
F) Stimulates Protein C & S
B) Releases tPA to prevent clot formation
E) Binds with AT3 to interfere with coagulation
F) Stimulates Protein C & S to inhibit clot formation
If you have a low Vit K and low INR, what do you give?
FFP
Protein C & S inhibit which coagulation factors?
A) 1, 5, 8, 13
B) 2, 7, 9, 10
C) 3, 5, 8
D) 10, 5, 2, 1
E) 11, 12, 9, 8
C) 3, 5, 8
AT 3 corrals which clotting factors to influence factor ll?
A) 1, 5, 8, 13
B) 11, 12, 9, 8
C) 2, 7, 9, 10
D) 10, 5, 2, 1
E) 12, 11, 10, 9
E) 12, 11, 10, 9
Fibrinolysis is highly regulated by?
plasma proteins
A clot is primarily composed of?
plasminogen, plasmin, fibrin and fibrin degrading products
How many days should aspirin be withheld prior to surgery?
A) 3-4 hours
B) 1-2 days
C) 24-48 hours
D) 7-10 days
E) 30 days
D) 7-10 days
Aspirin inhibits?
Inhibits cyclooxyrgenase (irreversibly), therefore decreasing PLT function
NSAIDS inhibit COX irreversibly. T/F
F
Inhibit Cox reversibly
NSAIDs should be withheld how many days before surgery?
A) 3-4 hours
B) 1-2 days
C) 24-48 hours
D) 7-10 days
E) 30 days
C) 24-48 hours
What is a normal bleeding time?
2-8 minutes
Bleeding time evaluates what?
PLT function & count & microvascular contraction
What is a normal PLT count?
150-300K/mm3
How low can your PLT be and still be sufficient for hemostasis?
100K
What PLT level would be mild thrombocytopenia?
50-100K
What PLT level would be severe thrombocytopenia?
<50K
Spontaneous bleed is rare, but may be prolonged in sx.
PLT < 20K will have spontaneous bleeding
What is the primary role of PLTs?
maintain vascular integrity
aggregate
initiate clotting cascade
What is a normal PT time
10-15 sec
Is PT affecting the intrinsic or extrinsic pathway?
Extrinsic
think PET - E for extrinsic
Extrinsic factors 3,7
What is a normal PTT value?
25-40 sec
Is PTT affecting the intrinsic or extrinsic pathway?
Intrinsic
think PITT - I for intrinsic
Intrinsic Factors 12,11,9,8
T/F. Any factor deficiency (intrinsic, extrinsic, or common pathway) will lead to increased risk of bleed.
False
For sure only factor 8,9 will cause bleeding if deficient (seen with hemophilia)
What is a normal INR?
less than or equal to 1.1 (normal healthy person)
2-3 (therapeutic range)
Book says overall (1.5-2.5)
What is a normal ACT?
90-150 sec
monitors ability to clot
What is a normal TT?
9-13 sec
it is a measure of fibrinolytic pathway
TEG benefits ability to evaluate?
PLT reactions
Coagulation
Fibrinolysis
TEG provides an indication of
Clot strength
PLT # & function
Intrinsic Pathway defect
Thrombin formation
Rate of fibinolysis
What labs help evaluate fibrinolysis?
DDimer
Fibrin degradation products
TEG
What are the 3 major reasons for transfusing in OR?
Replace volume
Replace coagulation factors
Improve oxygen carrying capacity
What is the recommended dose for PLT infusion?
1 unit/10kg BW
This should improve PLT count by 5-10K
What is the normal life span of PLT vs if it is donated?
Normal: 7-10 days
Donated: 4-5 days
PLTs pose a high risk of bacterial transmission. T/F
True.
They are stored at room temperature for 4-5 days making it an excellent medium for bacterial growth
How do we get FFP and what does it contain?
It is the fluid portion of whole blood, frozen to persevere it contents.
Contains: Coag factors and naturally occurring inhibitors
Doesn’t provide PLTs
What are alternatives to replace 1 unit of FFP?
4-5 PLT concentrates
1 unit single donor apheresis PLT
1 unit fresh whole blood
Cryo is rich in?
Factors 8, 13, 1
Fibronectin
VWF
When would you give cryo?
test indicates fibrinolysis
concentration of fibrinogen < 80-100mg/dL + bleeding
adjunct in MTP
congenital fibrinogen deficiencies
If desmopressin and vWF/Vlll concentrate are ineffective in try vWD, then cryo can be given
When do you use recombinant factor Vll?
Hemophilia A (Vlll) & B (lX)
Inhibitor disorders of Vlll & lX
Factor Vll deficiency
Universal hemostatic agent
*will reverse prolonged INR but not replace clotting factors
*caution in pts predisposed to thrombosis
Tx very expensive
suggested dose: 20-45 mcg/kg
A pt with an abnormal PT/INR and normal PTT would have what deficiency (ies)?
What is the treatment?
Factor Vll Deficient
Tx: FFP
A pt with an abnormal PTT and normal PT/INR would have what deficiency (ies)?
What is the treatment?
Factor Vlll, lX, Xl Deficient or on heparin tx
Tx: FFP, Protamine
A pt with an abnormal PT/INR and abnormal PTT would have what deficiency (ies)?
What is the treatment?
Factor X, V, ll Deficient
Dysfrbrinogen
Heparin (high level)
Warfarin
Vit K deficient
Liver disease
DIC
Tx: FFP, Cryo, Protamine
Abnormal BT and PLT count, what can you give to treat?
PLT concentrate
Abnormal BT, what can you give to treat?
PLT concentrate
Abnormal PT/PTT/INR, PLT count, & fibrinogen is low, what can you give to treat?
Pt is in DIC!
Tx: FFP, Cryo, PLT concentrate, whole blood
Abnormal PT, what can you give to treat?
FFP
Abnormal BT and PTT count, what can you give to treat?
vWD!
Tx: Desmopressin, vWF/Vlll, and if those don’t work then cryo
In liver disease, you will see a decrease in which clotting factors?
ll, Vll, lX, X & Fibrinogen
you will also see,
Vit K deficiency
Dysfibrinogenemia
enhanced fibrinolysis
DIC
Thrombocytopenia dt hypersplenism
What does this TEG indicate?
normal
What does this TEG indicate?
Anticoagulants/hemophilia
What does this TEG indicate?
PLT blockers
What does this TEG indicate?
Fibrinolysis
What does this TEG indicate?
Hypercoagulation
What does this TEG indicate?
DIC stage 1
What does this TEG indicate?
DIC stage 2
What happen to RBCs when they are stored for >7days?
-Decreased 2,3-DPG —Oxyhemoglobin shift to the left (love = reduced O2 release)
-Decreased ATP
-Decreased pH (d/t increased lactic acid
-Impaired ability to change shape
-Hemolysis
-Increased Potassium (caution in neonates and renal failure pts)
-Increased production of proinflammatory mediators
What are the functions of vWF?
1) facilitate platelet adhesion
2) plasma carrier for factor 8
**vWF synthesized by the endothelial cells and magakaryocytes
What labs will be abnormal in vWF disease?
1) prolonged BT and PTT (Apex)
2) decreased vWF (Nagelhout)
3) decreased vWF activity (measured by ristocetin (an antibiotic) cofactor essay
4) decreased factor 8
What are the treatment options for vWF disease?
1) Desmopressin
2) F8/vWF concentrate
3) IV immunoglobulins
4) cryo can be used only if ristocetin cofactor <50%
5) Tranexamic acid
What are the treatment options for hemophiliac patients?
-Factor 8 concentrate
-Desmopression 0.3mcg/kg
How does Warfarin work?
-Warfarin inhibit the enzyme vitamin K epoxide reductase complex 1, which is responsible for converting inactive Vit K to active (Apex)
What lab tests indicate DIC?
Increased PT, PT, D-dimer, FDP
Decreased Platelet, Fibrinogen
Who is at risk for DIC?
Sepsis (highest risk)
Postoperative
Obstetric
Blood transfusion reactions
Cancer
Treatment options for DIC
Treat the underlying cause
For DIC due to sepsis, antithrombin administration
what triggers sickle cell crisis?
hypoxemia
hypothermia
infection
dehydration
venous stasis
acidosis
What is the most common surgery among sickle cell patients?
Cholecystectomy due to excess bilirubin from rapid breakdown of sickle erythrocytes
What is the most common hemoglobin type in sickle cell disease (SCD)?
Hemoglobin S
What is the appropriate anesthesia management for patients with SCD?
provide adequate hydration
promote adequate oxygen saturation
ensure normothermia
maintain acid-base balance
provide proper patient positioning
Adequate pain management
Caution with vaso-oclusive devices such as tourniquets
For high risk procedure, decrease hemoglobin S level <30%
*preop blood transfusion is a debate
What are clinical signs of HIT?
-Decreased of >50% in platelet count from baseline or total platelet count <100,000 on heparin or LMWH
-S/Sx: thrombocytopenia, resistance to heparin, thrombosis, positive to assay tests
What test gives a definite dx to HIT?
C-serotonin release assay is the gold standard
Why does HIT type 2 have worse outcomes?
-Immunoglobulin G response
-Thrombocytopenia does not resolve spontaneously–> must d/c heparin
-associated with thrombosis
Which of the following drugs belong to the ADP receptor inhibitors?
a) ASA
b) clopidogrel
c) ticlopidine
d) ticagrelor
e) cangrelor
Platelet GP 2b/3a receptor blockers drugs
abciximab
tirofiban
eptifibatide
Direct thrombin inhibitors drugs
bivalirudin
dabigatran
Direct factor Xa inhibitors drugs
rivaroxaban, apixaban, edoxaban, betrixaban
When should the patient stop taking unfractionated heparin or LMWH?
6 hours or 12-24 hours before procedure
Pt had BMS (bare metal stent) implanted 15 days ago, pt is scheduled for an elective noncardiac surgery, you are the anesthesia provider, ok for surgery?
box 38.11
Elective non-cardiac surgery should be delayed 30 days after BMS implantation, 6 months after DES implantation
Should patient stop taking ASA while on dual antiplatelet therapy?
with dual antiplatelet therapy (DAPT) after coronary stent who must undergo surgical procedure that mandate D/c of P2Y12 inhibitor therapy (clopidogrel or ticagrelor), recommended that ASA should be continued
What component of blood product is appropriate for hemophilia A?
Preferred viral inactivated plasma derived or recombinant concentrates > Cryo > FFP
other treatments desmopressin (only works for Hemophilia A), tranexamic acid, and epsilon aminocaproic acid
What treatment is appropriate for Hemophilia B?
FFP, tranexamic acid, aminocaproic acid
What cause sickle cell disease? (SCD)
autosomal recessive genetic abnormality of the beta-globin gene
What are the triggers for SCD?
1) hypoxemia
2) hypothermia
3) infection
4) dehydration
5) venous stasis
6) acidosis
What is the most common surgery associated with SCD?
-Cholecystectomy for gallstones
d/t excess bilirubin from rapid breakdown of sickle erythrocytes
What are the anesthesia plan for SCD patients?
-adequate hydration
-adequate oxygen saturation
-normothermia
-acid-base balance
-proper positioning
-pain management
What are the antagonist drugs of Factor Xa?
Rivaroxaban
Apixaban
Endoxaban
Betrixaban
Fondaparinux
What is the antagonist drug of Factor 2a (Thrombin)?
Dabigatran
What drugs antagonize Glycoprotein 2b/3a?
Abciximab
Epitifibatide
Tirofiban
