Flashcards in Exsanguination Deck (133):
what are the four general steps of normal hemostasis?
1. capillary vasoconstriction
2. platelet plug formation
3. coagulation (fibrin formation)
4. fibrinolysis (occurs simultaneously)
what molecule is primarily responsible for the vasoconstriction and platelet aggregation during normal hemostasis? where is it released from?
- released from platelets
what molecule opposes TXA2 during normal hemostasis? where is it released from?
- released from endothelium
what is the lifespan of megakaryocytes?
1/3 of megakaryocytes are sequestered in the __________
what are the 4 steps of platelet plug formation?
3. granule release
platelets adhere to subendothelial collagen at site of injury mediated by _______ and _________
vWF and GpIb
platelet granule release is mediated by what two molecules? what is the result?
- result: exposure of fibrinogen receptors on platelet surface
what characterizes the aggregation phase of platelet plug formation?
fibrinogen crosslinking between platelets via GpIIb
all clotting factors are synthesized in the liver with the exception of:
- vWF (cofactor VIII)
these are synthesized in the endothelium
what is responsible for degrading Va and VIIIa?
protein C (with cofactor S)
what is the single best test to evaluate liver function?
how do the extrinsic and intrinsic pathways differ?
- extrinsic: release of TF from damage OUTSIDE the blood vessel
- intrinsic: injury to the blood vessel with release of clotting factors from circulation
the final common pathway results in:
conversion of fibrinogen to fibrin, and fibrin crosslinking
plasminogen is converted to ____________ by _________ / __________ / ___________
-TPA / urokinase / streptokinase
what is the primary signal of fibrinolysis?
TPA from endothelium
plasmin cleaves ____________, leaving ______________
- E and D fragments (D-dimer)
what are the inhibitors of fibrinolysis?
- primary: a2 antiplasmin (bound to fibrin, rapid acting)
- secondary: a2 microglobulin
what are the anti-fibrinolysis meds?
what is the MOA of the anti-fibrinolysis drugs amicar and aprotinin?
block plasmin and kallikrein
what is the MOA of the anti-fibrinolysis drug TXA?
lysine analog, blocks lysine receptors on plasminogen, more powerful than amicar
antithrombin 3 binds and inactivates what factors?
how does heparin work?
induces conformational change in antithrombin 3, increasing reaction rate 1000x (for inactivation of II, IX, X, XI)
what is the inheritance of antithrombin 3 deficiency?
what is the clinical presentation of antithrombin 3 deficiency?
- 20-50 yo
- widespread DVT and arterial thrombosis
- pt appears resistant to heparin
what is the treatment for antithrombin 3 deficiency?
- FFP (replenishes AT3)
- lifelong anticoagulation
less than ___% normal level of protein C/S leads to hypercoagulable state
less than 60%
what is the inheritance of protein C/S deficiency?
what is the pathogenesis of factor V leiden?
factor V resistance to activated protein C due to single amino acid substitution of arginine to glutamine
what is the inheritance of factor V leiden?
what is the pathogenesis of acquired hypercoagulable state?
liver failure can lose AT3 and have a picture like AT3 deficiency
what do the blood studies show in vWF disease?
- normal platelet count
- slightly prolonged PTT
hemophilia A = factor _____ deficiency
what is the inheritance of hemophilia A?
what are the blood labs for hemophilia A?
- increased PTT
*obtain factor assay
what is the treatment for hemophilia A?
- increase factor VIII when hemostatic challenge is anticipated
- factor VIII concentrate treatment of choice, but can also give cryoprecipitate
- dose BID
- need 70-100% activity for major surgery, 40-50% for minor surgery
hemophilia B = factor ____ deficiency
what is the inheritance of hemophilia B?
what do blood labs show for hemophilia B?
*obtain factor assay
what is the treatment for hemophilia B?
- cryoprecipitate, dose daily
- need 50% activity for major surgery
which is worse - type 1 or 2 HIT?
what is the cause of type 2 HIT?
- immune-mediated, results in platelet aggregation and activation, then clearance in reticuloendothelial system
- initially predisposed to thrombosis, then thrombocytopenia and hemorrhage
"white clots" on pathology is indicative of:
how is HIT diagnosed?
14C serotonin release assay / ELISA
*look for platelet clumping in presence of therapeutic heparin dosing
what is the treatment for HIT?
- stop heparin
- use direct thrombin inhibitor (lepirudin, argatroban, coumadin) in setting of thrombosis
what are some direct thrombin inhibitors?
what do the blood labs show with DIC?
- decreased platelets
- increased fibrin split products
- increased PT and PTT
what is the treatment for DIC?
- treat underlying cause
- give platelets, FFP, cryoprecipitate
what is the shelf life of whole blood? what is lost after 24 hrs?
- 35 with addition of citrate phosphate dextrose
- store at 4C
- platelets, factor V, VII lost in 24 hr
1 unit of pRBC should raise HCT by ___% in a 70kg person
what is the shelf life of pRBC?
what is the best blood product option to improve O2 capacity without hypervolemia?
how long can platelets be stored for?
when is a platelet transfusion indicated?
platelet count under 100k or 50k in patients requiring surgery
______thermia (hypo/hyper) makes platelets unable to produce TXA2
_____ mL/kg FFP should replete coagulation factors to levels required for hemostasis?
FFP is stored at what temp?
-18C (to protect factors V, VIII)
does FFP require typing, crossmatch, both, or neither?
typing, but not crossmatch
what are the indications for FFP?
- coagulopathy of liver disease
- vitamin K deficiency
- coumadin therapy
- dilutional coagulopathy
- AT3 deficiency
what does cryoprecipitate contain?
- factor VIII
- factor XIII
how is cryoprecipitate prepared?
plasma frozen to -90C, warmed slowly to 4C - precipitate which forms is separated with a small amount of plasma
what are the indications for cryoprecipitate?
- source of vWF in vWD
- source of factor VIII in hemophilia A
- source of fibrinogen in DIC
what is the presentation for febrile non-hemolytic transfusion reaction?
- isolated fever 1-6h after transfusion
- flank pain
- red/brown urine
what is the pathophysiology of febrile non-hemolytic transfusion reaction?
complement mediated destruction of transfused cell components by pre-existing antibodies
what is the treatment for febrile non-hemolytic transfusion reaction?
- use buffy coat poor RBCs in the future
what is the presentation of hemolytic transfusion reaction?
- chest pain
- flank pain
- acute renal failure
when does hemolytic transfusion reaction occur?
within first 50cc of blood
what is the treatment for hemolytic transfusion reaction?
- stop transfusion, recheck ABO
- hydrate to UOP > 100cc/hr (mannitol, lasix, bicarb)
what is the pathophysiology of hemolytic transfusion reaction?
ABO incompatibility, personal errors
what is the pathophysiology of delayed hemolytic transfusion reaction? how does it present?
- minor blood group antigen incompatibility
- days later: fever, chills, jaundice
what is the treatment for delayed hemolytic transfusion reaction?
hydrate to UOP > 100cc/hr (mannitol, lasix, bicarb)
what is the frequency of blood products as cause for TRALI?
FFP > PLT > RBC
what is the treatment for TRALI?
- AVOID DIURETICS
what does thromboelastograph (TEG) test?
how does the thromboelastograph (TEG) test work?
- sample of whole blood placed in warmed cuvette
- pin lowered into blood, rotated backward and forward
- fibrin strands interact with activated platelets on the surface of the pin, rotational movement of the cuvette transmitted to pin
- stronger the clot, the more the pin moves
- pin movement connected to computer that displays the coagulation profile
what does the R time indicate for the thromboelastograph (TEG) test?
initiation: time from initiation of test to initial pin movement / initial fibrin formation
what does a prolonged R time mean for thromboelastograph (TEG) test? what is the treatment?
factor deficiency - treat with FFP
what does the K value indicated for the thromboelastograph (TEG) test?
amplification: time to achieve clot strength, due to thrombin and platelet activation
what does the alpha angle represent for the thromboelastograph (TEG) test?
- measures the speed at which fibrin buildup and cross linking takes place (clot strengthening)
- assess rate of clot formation
what does a prolonged K / reduced alpha angle mean for the thromboelastograph (TEG) test? how is it treated?
fibrinogen deficiency - treat with cryoprecipitate
what is the maximum amplitude for the thromboelastograph (TEG) test?
- function of the maximum dynamic properties of fibrin and platelet bonding via GpIIb/IIIa
- represents the strongest point of fibrin clot and correlates with platelet function
what does a reduced maximum amplitude mean for the thromboelastograph (TEG) test? how is it treated?
- platelet dysfunction
- treat with platelets or ddAVP
what does the clot lysis index (LY30) measure for the thromboelastograph (TEG) test?
- give a measure of degree of fibriniolysis
- clot stability: percentage decrease in amplitude 30 minutes post-maximum amplitude
what does an elevated LY30 mean for the thromboelastograph (TEG) test? how is it treated?
rapid clot lysis - treat with TXA
what parameter represents the strongest point of fibrin clot and correlates with platelet function for the thromboelastograph (TEG) test?
what parameter determines the function of the maximum dynamic properties of fibrin and platelet bonding via GpIIb/IIIa for the thromboelastograph (TEG) test?
what parameter of the thromboelastograph (TEG) test gives a measure of degree of fibrinolysis?
clot lysis index (LY30)
if you suspect a fibrinogen deficiency what parameter(s) would you look at for the thromboelastograph (TEG) test?
K value and alpha angle
if you want to assess the rate of clot formation which parameter(s) would you look at for the thromboelastograph (TEG) test?
if you want to determine the time to achieve clot strength what parameter would you look at in the thromboelastograph (TEG) test?
what is the half life of heparin?
dose dependent (45-150 min)
how is heparin removed from the body?
RES and kidneys
how is heparin function followed?
PTT (want 50-80s)
how is heparin reversed?
- protamine sulfate - give 1mg/100u heparin administered in preceding 2 hrs
- cross reacts with NPH insulin
what is the MOA of LMWH?
inhibits factor X over thrombin (4:1 ratio), with greater bioavailability
what are the advantages of LMWH?
- 2-4x longer half life
- excreted through kidney
- more predictable response to fixed doses
how do you measure LMWH activity?
how is LMWH (Lovenox) reversed?
protamine sulfate: 1mg/mg Lovenox if given within 8 hrs; 0.5mg/mg Lovenox if over 8 hrs
what is the MOA of synthetic oligosaccharides in anticoagulation?
- bind to AT3, induce conformational change
- accelerate elimination of factor X
- analogous to pentasaccharide sequence in heparin
what type of drug is fondaparinux (Aristra)? what is the route?
- selective Xa inhibitor
what are the indications for the selective factor Xa inhibitor fondaparinux (Aristra)?
- DVT proph
- DVT/PE treatment
how is the selective factor Xa inhibitor fondaparinux (Aristra) cleared?
- hepatic (66%)
- renal (33%)
how can selective factor Xa inhibitor (e.g. fondaparinux (Aristra)) activity be monitored?
what is used to reverse selective factor Xa inhibitors fondaparinux (Aristra)?
Novoseven 90mc/kg (recombinant factor VII)
what type of drugs are rivaroxaban (Xarelto) and apixaban (Eliquis)? what are the routes?
- selective factor Xa inhibitors
what are the indications for rivaroxaban (Xarelto) and apixaban (Eliquis)?
- DVT proph
- DVT/PE treatment
- ACS treatment
when are direct thrombin inhibitors used?
use in patients with heparin contraindications
how do direct thrombin inhibitors affect blood labs?
- all will increased PTT
- must shoot for high INR if bridging to coumadin
what are the half lives of the direct thrombin inhibitors?
- lepirudin: 90 min
- bivalrudin: 25 min
- argatroban: 45 min
- dabigatran: 7-9 hr
what are the clearance routes for the direct thrombin inhibitors?
- lepirudin: renal
- bivalrudin: renal
- argatroban: hepatic
- dabigatran: renal
what are the routes for the direct thrombin inhibitors?
- lepirudin: IV/SC
- bivalrudin: IV
- argatroban: IV
- dabigatran: PO
how do you monitor the activity of direct thrombin inhibitors?
PTT (except for dabigatran - thrombin time)
how is coumadin reversed for life threatening bleeding?
- vitamin K 10g IV over 10 min
- 4u FFP
- r-factor PCC (Kcentra) preferred
- INR 1.5-3.9: 25u/kg PCC
- INR 4.0-6.0: 35u/kg PCC
- INR over 6.0: 50u/kg PCC
what is the MOA of aspirin?
irreversibly inhibits COX; decreases prostacyclin and platelet thromboxane
how long do the effects of aspirin last? when should it be d/c'd before surgery?
- effect for 7-10d
- dc one week prior to surgery
what is the MOA for NSAIDs?
reversible COX inhibitors
what is the MOA of dipyridamole?
inhibits adenosine deaminase and phosphodiesterase, inhibits platelet aggregation
*dosed with ASA as aggrenox
what are the GpIIb/IIIa inhibitors?
- abciximab (Reopro)
- eptifibatide (Integrilin)
- tirofiban (Aggrastat)
are what type of drugs?
direct thrombin inhibitors
when are the GpIIb/IIIa agents used?
ACS / PCTA stenting
what is the half life of the GpIIb/IIIa agents?
what is the MOA of ticlopidine and clopidogrel?
platelet aggregation inhibitors - irreversibly block binding of the ADP receptor
*stronger effect than ASA
how are the platelet aggregation inhibitors (ticlopidine and clopidogrel) metabolized?
how long does it take for the platelet aggregation inhibitors (ticlopidine and clopidogrel) to start working?
how long before surgery should the platelet aggregation inhibitors (ticlopidine and clopidogrel) be held?
which of the platelet aggregation inhibitors (ticlopidine and clopidogrel) requires first pass liver metabolism?
Plavix (clopidogrel) - do not use in liver failure patients
what are the platelet aggregation inhibitors that block the p2y12 receptor for ADP?
- prasugrel (Effient)
- cangrelor (IV)
- ticagrelor (Brilinta, PO)
how do cangrelor and ticagrelor differ from prasugrel?
- cangrelor and ticagrelor are direct and reversible inhibitors, and do NOT have p450 activation
- very rapid onset/offset
how does dextran work?
- thrombi undergo lysis at an increased rate
- decreased platelet adhesion and aggregation
the platelet function assay depends on what factors?
- plasma vWF level
- platelet number
how does the platelet function assay work?
- small membranes coated with collagen and EPI or collagen and ADP
- anticoagulated whole blood passed through membranes at high shear rate to simulate in vivo hemodynamics
- time for blood to occlude membrane is the closure time
- col/EPI done first
- if col/EPI is prolonged, col/ADP reflexively performed
what are the interpretations for the col/EPI and col/ADP tests for PFA?
- col/EPI done first
- closure time under 183s excludes presence of defect
- if col/EPI is prolonged, col/ADP reflexively performed
- if col/ADP is NORMAL (under 122s), ASA induced platelet function is most likely