Blood/Hemostasis Flashcards
ch 27, 28, 29, 30 10 questions
What are the 3 main steps of coagulation?
- vascular spasm
- platelet plug formation
- blood clot formation/coagulation
(4. then permanent fibrous tissue eventually closes the hole in the vessel)
How do platelets know to go to site of injury?
they release chemical mediators that attract them
What occurs in the tissue injury phase of hemostasis?
- vascular spasm
- platelet plug
- fibrin cross linked
What occurs in the tissue repair phase of coagulation?
Fibrinolysis of the fibrin clot to restore normal state of blood flow
What is the purpose of vascular constriction after vessel injury?
Prevents blood loss and allows procoagulants to remain locally and work in injured vessels
What mediators encourage platelets to release vWF?
GP1a, GP2a, GP5
What substance binds platelets to subendothelium?
vWF
What activates platelets?
negatively charged surfaces such as collagen secreted from the endothelium in response to injury
What substance recruits other platelets to assist in plug formation?
ADP and Thromboxane A2
What do activated platelets secrete and what is the purpose of these subastances?
Fibrinogen, vWF, and platelet growth factor. They increase efficiency of aggregation and adherence
Excessive clotting would occur without:
Nitric oxide, ADPase, prostacyclins, thrombomodulin, CD-39
What 3 things things encourage vessel constriction?
- Nervous reflex (smoothm.)
- Local myogenic spasms
- Local humoral factors released from traumatized tissue/platelets (thromboxane A2 vasoconstrictor)
What does Von Willebrand disease affect in the clotting cascade?
Platelet adherence to the subendothelium
How long does it take for blood clot formation to occur?
mild trauma: 1-2 minutes
severe trauma: 15-20 seconds to 6 minutes depending on severity of the trauma
What occurs 20min-1 hour after blood clot formation?
clot retracts, aiding in vessel closure
What cause the clot to becomes fibrous connective tissue?
clot is invaded by fibroblasts that form connective tissue and then allows the clot to be dissolved by plasmin
What is prothrombin and how does it aid in coagulation?
Prothrombin is a substance produced in the liver that is converted to thrombin via Ca+2 and prothrombin activator which transforms fibrinogen into fibrin monomers while also activating fibrin stabilizing factors. this assists in clot formation
What substance is needed to produce prothrombin and where does this occur?
liver, vitamin K
In the thrombin pathway, what are the two places calcium is needed?
- prothrombin to thrombin
- fibrin monomers to fibrin fibers
What factor covalently bonds to fibrin?
Factor VIII (eight): antihemophilic factor, that assists in stabilizing the clot
also works as a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa.
Hemophilia A is a deficiency of:
Factor VIII (eight)
What are the two pathways of prothrombin activator formation?
Extrinsic: trauma to vessel/exposure to tissue factor at site of injury
Intrinsic: occurs in blood
Mnemonic for clotting factors:
- Fibrinogen- foolish
- Prothrombin- people
- Tissue factor- try
- Calcium ions- climbing
- Labile factors (proaccelerin)- long
- Stable factors (proconvertin)- slopes
- Antihemophilic factor- after
- Christmas factor- Christmas
- Stuart-Prower factor- some
- Plasma thromboplastin antecedent- people
- Hageman factor- have
- Fibrin stabilizing factor- fallen
By exception, where are the clotting factors synthesized?
all liver EXCEPT: calcium (diet), tissue factor/thromboplastin (vascular wall), vWF (endothelial cells and platelets)
What lab test is best used for each coagulation pathway?
intrinsic: aPTT/ACT
extrinsic: PT/INR
When do the two clotting pathways come together to form the common pathway?
at factor X
What factors are used in the extrinsic pathway?
Factor 7 (VII) and factor III (3)
What factors are used in the intrinsic pathway?
Factor 12 (XII), 11 (XI), 9, (IX), and 8 (VIII)
What three things are needed for factor X to move forward in coagulation?
Factor V, lipids, and calcium
What factors are vitamin K dependant and are not?
are: 2, 7, 9, 10
aren’t: 1, 5, 8, 11, 12, 13
Explain: for 37 cents you can buy the extrinsic pathway
- tissue factor released activates
- factor X activation: tf activates 7, then 7 activates 10 in the presences of 4 (ca+2)
- prothrombin activator: prothrombin activator and platelet phospholipids activate 2 (thrombin), 5 is a positive feedback mechanism that accelerates production of prothrombin activator to continue
What activates the extrinsic pathway?
the release of tissue factor from the subendothelium
What occurs after the extrinsic pathway is activated?
TF activates 7 > 7 and ca activates 10 > 10a, prothrombin activator and phospholipids activate 2 (thrombin) > thrombin feeds factor 5 to continue production of prothrombin
What causes the intrinsic pathway to begin?
blood trauma/collagen exposure
What is the process of the intrinsic pathway?
blood trauma/collagen exposure > activates XII > XIIa activates XI (requires HMW, accelerated by prekallikrein> XIa and calcium activate IX > thrombin activates VIII > VIIIa, X, ca+2, phospholipids, platelets, and IXa activate X > thrombin, Xa, platelets, phospholipids, ca+2 release prothrombin activator to convert prothrombin into thrombin
What is the mnemonic for the intrinsic pathway?
If you cant buy the intrinsic pathway for $12, you can buy it for $11.98
What step is identical in the intrinsic and extrinsic pathways?
Prothrombin activator/last step
What drug inhibits that extrinsic pathway?
Coumadin/warfarin
What drug inhibits the intrinsic and final common pathway?
Heparin
What is the mnemonic for the final common 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”
factor 5, 10, 1, 2, 13
What steps in the coagulation cascade do not use calcium?
first two steps
What endogenous substances are procoagulants?
Coagulation factors
Collagen
wVF
Fibronectin
What are endogenous anticoagulants?
Protein C
Protein S
Antithrombin
Tissue pathway factor inhibitor
Thrombomodulin
What endogenous substances are fibrinolytics?
Plasminogen
tPA
Urokinase
What endogenous substances are antifibrinolytics?
Alpha-antiplasmin
Plasminogen activator inhibitor
What is things are inside a platelet?
actin, myosin, thrombosthenin, ADP, ca+2 (4), fibrin stabilizing factor (13), serotonin, growth factor
What things are on the external membrane of platelets?
glycoproteins and phospholipids
What three things must occur to make a platelet plug?
adhesion, activation, agregation
Hageman factor is used in which pathway?
Intrinsic
Which coagulation pathway is faster?
Extrinsic, occurs in about 15 seconds
What factor is depleted first in a patient vitamin K deficiency?
Factor VII (7)
What three factors are specific to the classical intrinsic pathway?
Factors 11, 9, 8 (12 is in both)
What type of surgery significantly increases risk of DVT?
Hip surgery
How does heparin work?
binding to antithrombin III which prevents conversion of fibrinogen to fibrin. inhibits X and thrombin. AT3 bind increases anticoag effects. Neutralizes thrombin (IIa), factors 9a, 10a, 11a, 12a
What is the dosing for heparin?
cardiac surgery: 300-400u/kg
DVT prophylaxis: 5,000u sq bid/tid
Unstable angina/acute MI: 5000u iv then 1,000u/hr infusion
What is the onset of action of heparin?
SC: 1-2 hours
IV: instant
What are the two major side effects of heparin?
HIT, Hemorrage
T/F heparin is safe to use with neurological procedures, HIT, and regional anesthesia
FALSE
What is the dosage for heparin reversal via protamine sulfate?
1mg for every 100 units of heparin less than 30 min after admin
0.75mg for every 100 units if 30-60min since admin
What is the goal ptt for heparin anticoagulation?
normal: 30-35 x 1.5-2.5 patients baseline
What two things can cause a falsely high PTT?
patients temperature and hemodilution
What individuals are at a high risk of anaphylactic reaction to protamine?
taking NPH insulin, fish allergy, vasectomy, previous exposure
What is the goal ACT for an individual being anticoagulated with heparin?
> 250
Where is endogenous heparin produced?
liver, basophils, mast cells
How does protamine work and how long does it take?
covalently/irreversibly binds to heparin, about 5 minutes for circulation time, short half life of 10 minutes
Does protamine work for LMWH?
not fully, difficult to differentiate
What are side effects of protamine?
anaphylaxis, pulm htn (give peripheral), hypotension, bradycardia
*treat with antihistamines, H1 blockers, H2 blockers, steroids, albuterol
What is HIT and what causes it?
Heparin induced thrombocytopenia is excessive clotting which causes a 50% drop in platelets 4-5 days post heparin dose. caused by heparin antibodies to platelet factor IV, triggers aggregation
Why does heparin to cause an adverse reaction of Pulmonary hypertension?
Due to the release of thromboxane A2
How should HIT be managed when diagnosed?
stop heparin, start non heparin such as bivalirudin to bridge to warfarin long term or a direct factor Xa inhibitor such as xarelto
What are the pros and cons of LMWH?
pros: less protein bound (high bioava), most consistent dose, potentially better at VTE proph, good for pregnancy
cons: renal dose, no reversal, spontaneous hematoma w spinal and epidural catheters
What is the choice anticoagulant for a pregnant woman?
LMWH
What is the onset time of LMWH?
20-30 minutes
T/F parental direct thrombin inhibitors have a reversal agent:
FALSE
What are some examples of parenteral direct thrombin inhibitors and how do they work?
bivalirudin, argatroban, lepirudin/desirudin- work by irreversibly binding to thrombin (IIa inhibitors)
What patients would benefit from a parenteral direct thrombin inhibitor?
HIT, renal dysfunction, heparin induced skin reactions
What patients frequently receive bivalirudin and what is its half life?
unstable angina/PCI, off label for cardiac surgery, and HIT. Half life is 25 minutes
What drugs are frequently given with bivalirudin?
aspirin and plavix
How is argatroban eliminated and what is its half life?
Hepatically, fine for renal failure, half life 40 minutes
How long does argatroban need to be stopped for coagulation to return to baseline?
4 hours
What are the not preferred effects of lepirudin and desirudin?
L: direct antibodies produced, major renal clearance
D: anaphylaxis
What are the half lives of Lepirudin and Desirudin?
L: 80 min
D: 60 min IV, 120 min subq
Whats a major difference between lepirudin and desirudin?
Lepirudin requires lab monitoring while desirudin doesnt
How does warfarin work and what is it’s half life?
it is a vitamin K antagonist so it inhibits activation of vitamin K dependant factors (II, VII, IX, X) and protein S and C
Half life is 24-36 hours, onset 8-12 hours
Is warfarin safe in pregnancy and patients with renal failure?
NO: highly protein bound, crosses placenta and can have dramatic effects on fetus
What are the perks of warfarin?
predictable in onset, duration, and great bioavailability.
can be affected by leafy greens rich in vitamin K
What are common warfarin dosages and lab test?
2-10mg, INR test want 2-3 times control
How should warfarin be reversed?
Quickly: Kcentra (first line), FFP
Slowly: Vitamin K
Surgical considerations for warfarin:
Check inr
minor surgerys ok
dc 1-3 days prior to major surgery pt/inr should be within 20% baseline
compression neuropathy in brachial artery puncture
What are some considerations and dose for Vitamin K (phytonadione) administration?
must be given slow 1mg/min due to anaphylaxis risk. takes a couple hours to take effect.
Dose: 10-20mg po, IM, IV
What are some examples of Xa inhibitors?
Rivaroxaban (Xarelto), Apixaban
What is the mechanism of action of direct factor Xa inhibitors?
inhibits all forms of Xa which prevents the conversion of II into active form
What is xarelto good at preventing?
stroke and systemic embolism in patients with non valvular atrial fibrillation (as does apixaban)
What anticoagulant is suitable for patients undergoing knee and hip replacement?
rivaroxaban or apixaban
epidural catheter management with rivaroxaban should follow:
catheter should be removed no earlier than 18 hours after last dose and next dose should not be given earlier than 6 hours after removal
What reverse rivaroxaban and what test can measure the level?
prothrombin complex concentrates (PCC), reverse effects in healthy patients. anti-Xa is the lab test
What are the concerns with the use of new oral anticoagulants?
can increase surgical bleeding, no antagonists, no monitoring labs, not predictable
When should new oral anticoagulants be stopped and restarted in relation to surgery?
low risk: stop 24 hrs prior, restart 24 hrs post op
medium/high risk: stop 5 days prior, resume when all bleeding stops
How should patients taking new oral anticoagulants be managed for surgery?
postpone procedure for at least for a minimum of 1-2 half lives.
What is the mechanism of action of aspirin?
as an antiplatelet, it works by irreversibly acetylates cyclooxygenase which prevents the formation of thromboxane A2
How is aspirin cleared, and when should it be stopped and resumed after surgery?
rapidly cleared but has effects 7-10 days, for the entire lift of the platelet. should be stopped 7-10 days before surgery and resumes 24 hours after surgery
What are thienopyridines used for?
treats PVA, stent thrombosis prevention, stroke
What are examples of thienopryidines?
clopidogrel (plavix), prasugrel (errient), and ticagrelor
How is the MOA of thienopryidines?
P2Y12 receptor antagonist inhibits ADP mediated platelet activation antithrombotic
What is dual antiplatelet therapy and why is it recommended?
use of a thienopyridine and aspirin for patients with ACS and PCI
When should thienopyridines be discontinued prior to surgery?
seven days
What are some examples of Platelet Glycoprotein IIb/IIIa Antagonists and their uses?
abciximab (reopro)- PCI
tirofiban (aggrastat)- ACS
eptifibatide (intrgrelin)- PCI and ACS
What is the antidote for Platelet Glycoprotein IIb/IIIa Antagonists?
Dialysis
What is the common side effect of Platelet Glycoprotein IIb/IIIa Antagonists?
thrombocytopenia
What anticoagulant can be used with an indwelling epidural?
heparin
What is the min time between last dose of heparin, epidural placement, and next dose?
4-6 hours prior, and 4-6 hours after placement for next dose
How should you manage a heparin drip for a patient needing an epidural?
stop 4-6 hours for an aPTT <40
minimum time between LMWH dose and epidural placement/removal?
place 24 hours after dose, next dose 4 hours
What are the two antifibrinolytic agents?
Epsilon aminocaproic acid (amicar)
Tranexamic acid (TXA)
What is the MOA of antifibrinolytic agents?
competitively inhibit activation of plasminogen to plasmin at high doses inhibiting plasmin
What surgery is Amicar most commonly indicated for? What is the dose?
cardiac surgery; 15g total, 5g induction, 5g on pump, 5g post protamine OR simple IVP 5mg and gtt at 50ml/hr MAX 30g/day
What surgeries are TXA most commonly used in?
OB (PPHem), total joints/ortho/spine, sepsis, heavy menstrual bleeding
what are the adverse effects of amicar and a MAJOR thing to remember?
hypotension, bradycardia, arrhythmia, DONT give in same line as blood
How can TXA be useful in surgery?
prevent the need of blood transfusion
TXA dosages:
ortho: 20mg/kg IV, 2g joint
hemorrhage: adult 0.5-1g
peds: 10mg/kg and 1mg/kg/hr
TXA distribution, elimination, contraindications:
D: widely distributed, crosses placenta, breast milk
E: 2hr half time
C: vascular disease, kidney disease, clotting issues, past stroke, MI
What can TXA NOT be administered with and why?
Factor IX (9) complex concentrate/anti-inhibitor coag concentrate (major increase in thrombosis risk)
What is a major complication with TXA?
Blocks GABA in frontal cortex which can result in seizure and increased need of prop/sedation
minor: bleeding, mltiorg failure, vascular occlusion
What are some examples of antifibrinolytic agents?
Protamine, DDAVP, fibrinogen, recombinant activated factor 7a (novoseven), cryo
What are the indications for protamine, MOA, and dosages? What can occur if too much protamine is given?
heparin reversal, neutralizes heparin, inhibits platelets. 1-1.3 mg for every 100u of circulating heparin- over 5-15min
T/F: protamine only reverses UFH and should be given peripherally to minimize risk of PH?
TRUE
If 10,000u of heparin was given 30 minutes ago how much remains and how much protamine should be given for reversal?
30min half life; so 5,000u would remain 5000/100 = 50mg of protamine should be given over 5-15 minutes
What is heparin rebound and how should it be managed?
unbound heparin is in plasma after protamine clears, generally occurs 2-3hr after first dose and should be treated with more protamine
What does desmopressin (DDAVP) treat? MOA?
hemophilia A and B, vWF disease, DI, and bed wetting
Stimulates release of vWF and factor VIII (8)
DDAVP: dose, onset, 1/2 life, adverse effects, OD
d: hem A: 4 mcg/kg when factor VIII coagulant activity levels are <5%
Hemo B: 30min before surgery 0.1-0.4 mcg/kg over 10mins
DI: 4mcg/kg
peds: not used if less than 3 months old, for children less than 12 has not been est
Onset: 30 minutes
Half-life: 30 mins
AE: hypotension, HA, nausea, cramp, h2O intox, low na
OD: confus, HA, urinary/fluid retention
TX: decrease dose or stop
What is the indication, MOA, and dosage for fibrinogen?
Trauma, surgery, prolonged CPB run. to restore normal clotting function. vial 900-1300mg/90-130% vial.
bleeding increases with every 100mg/dL decrease. may not work in hypothermia, acidosis
Is fibrinogen considered a blood product and what are side effects associated?
yes, increased inflammation
What Neuro-Psych medication class can interfere with platelet aggregation, Why? What is the mechanism:
SSRIs increase serum serotonin which increases platelet aggregation, thus leading to a higher risk of clotting…. can increase both risk for clotting AND risk for bleeding???
What are the indications for Factor VII (7) and the adverse effects?
I: Hemo A&B, cardiac pts, uncontrolled head bleed
AEs: MI, stroke, DVT, PE
Factor VII MOA and dosing:
works in common pathway by binding to active platelets and activates factor X which improves thrombin production
Dose: Hem A&B- 90mcg/kg q2h achieve hemostasis or preop prophylaxis
What is cryoprecipitate and what are it’s indications and side effects?
prepared by thawing FFP: concentrated clotting factors (FVIII, vWF, FXIII, fibrinogen and fibronectin) 150-250mg fibrinogen
SE: donor exposure, thrombosis
dose: 6-10 units
what three things are indicated for hypofibrinogenemia?
- Fibrinogen: not discussed as much
- Cryoprecipitate: only when fibrinogen is <100-150 w no clotting def/last line
- FFP: mostly used for warfarin reversal when kcentra is unavailable
How much does cryo increase fibrinogen?
100mg/dL/5kg
What are indications for prothrombin complex concentrates(REIBA & Bebulin) and what are they?
I: Warfarin reversal, increased INR with urgent reversal
contains: F II, VII, IX, X
other warfarin reversal agent: FFP
What should be given (1st line) for vWFD or hemophilia prior to giving cryo, fibrinogen, or FFP?
DDAVP (stimulates release of vWF and factor VIII)
Side effects and dosage of bebulin:
D: 30-50iu/kg for active blood w/ anticoag, low dose: 20-25iu/kg soft tissue (doses based on pt/inr)
SE: thrombosis
What condition is Bebulin contraindicated in?
DIC
What is in FFP?
Procoag and anticoag factors, albumin, and immunoglobulins
What type of coagulation promotion is frequently used in cholecystectomy?
topical hemostatic agent such as
surgicel (oxidized cellulose): good for local hemostasis
tisseel (fibrin sealant): good for venous oozing
gel foam (gelatin sealant): small capillary bleeds
Failure of what organ should be considered in the setting of hemorrhage?
Liver
What things should be given to prevent need of blood transfusion in JWs?
iron, erythropoietin, DDAVP, antifibrinolytics, F XII
consider synthetics and human derivatives
What is the most important Thrombolytic and what are considerations?
tPA
Increased bleeding risk (no sticks)
What two drugs shouldnt be given with tPA?
nitro decreases effectiveness
aspirin increases toxic effects
What two substances should be associated with platelet activation and aggregation?
ADP and Thromboxane A2
How many half-lives should pass before considered back to normal coagulation function?
5 half lives
How long does the intrinsic pathway take to form a clot?
up to 6 minutes
What is the primary goal of both extrinsic and intrinsic coagulation pathways?
produce prothrombin activator
What is the role of Thrombin and what substance is needed to convert them into fibrin fibers?
Converts fibrinogen to fibrinogen monomer (active form), calcium
What is Plasminogen?
Proenzyme synthesized in the liver that is incorporated into the clot during formation- activated by plasmin activator becomes plasmin that breaks down clot
What is plasmin?
plasminogen activated by tPA and Urokinase to make plasmin which is a Proteolytic enzyme that degraded fibrin into fibrin degradation products
What two enzyme inhibitors turn off the fibrinolytic process?
tPA inhibitor and Alpha-2 antiplasmin
What is the dose for DDAVP?
0.3mcg/kg IV
What role does calcium play in the coagulation cascade?
activates platelets and F 2, 7, 9, 10, prothrombin
speeds coagulation and synthesizes protein C
What is in Kcentra?
VIIa, XIII, PCC (4 Factor), II, VII, IX, X
When should warfarin be stopped prior to surgery?
2-4 days
Patients with ____ need renal dosing for LMWH
Renal disease
Calcium is required for all blood clotting with the exclusion of the first ___ steps in the ________ pathway
2, intrinsic
What treatment could potentially cause calcium to become low enough to alter coagulation?
CVVHDF (CRRT) and HD
What type of feedback system is blood coagulation considered?
Negative feedback
What 2 actions are the goals achieved in the common pathway?
- prothrombin -> thrombin (CP acts as check/balance)
- fibrin fibers formed/activated
How long does it take heparin to work?
virtually instantly but 5 mins required for circulation
when should we check an ACT to assess heparinization?
surgeon request or 1 hour post dose
What factor does LMHW act on?
Xa
What are s/s of HIT?
signs of DVT/PE
limb necrosis
MI/Stroke
venous gangrene
HTN, tachy, CP, SOB
T/F both HIT-1 and HIT-2 require treatment
False, HIT-1 does not require any treatment
Which medication should be used with caution in patients with renal failure: heparin or LMWH?
LMWH
Why is the use of LMWH more concerning that heparin in the use of epidurals/spinals?
lack of reversal and long DOA
What anticoagulant is hepatically metabolized (and can be given to patients with renal failure?
argatroban
What is the anticoagulant of choice in a patient with a HIT induced AKI?
argatroban
What is warfarins half time and how is it excreted?
24-36hr, excreted in bile
T/F apixaban can easily be reversed with FFP
FALSE, difficult to reverse… FFP doesnt even reverse it
What the MOA of TXA?
allows formation of stronger fibrin mesh, prevents breakdown of clots, completely inhibits breakdown of fibrin clots by blocking activation of plasminogen
What is an anesthesia consideration for giving DDAVP?
give dose 30-60 secs to work prior to procedure
What should be given to a pt with hemophilia A or B prophylactically prior to surgery?
F VIII and IX
What are indications to give cryoprecipitate?
tx vWF, hemophilia when direct concentr. not available. rapid transfusion protocol, active OB bleed, hypofibrinogenemia
What are anesthesia considerations regarding PCC?
primarily used for warfarin reversal, esp in pts experiencing life threatening bleed w/ high INR
What is the treatment of coagulopathies such as vWF and hemophilia?
- missing factor
- Kcentra
- FFP
- Cryo
