Exsanguination Flashcards
(133 cards)
1
Q
what are the four general steps of normal hemostasis?
A
- capillary vasoconstriction
- platelet plug formation
- coagulation (fibrin formation)
- fibrinolysis (occurs simultaneously)
2
Q
what molecule is primarily responsible for the vasoconstriction and platelet aggregation during normal hemostasis? where is it released from?
A
- TXA2
- released from platelets
3
Q
what molecule opposes TXA2 during normal hemostasis? where is it released from?
A
- prostacyclin
- released from endothelium
4
Q
what is the lifespan of megakaryocytes?
A
8d
5
Q
1/3 of megakaryocytes are sequestered in the __________
A
spleen
6
Q
what are the 4 steps of platelet plug formation?
A
- adherence
- activation
- granule release
- aggregation
7
Q
platelets adhere to subendothelial collagen at site of injury mediated by _______ and _________
A
vWF and GpIb
8
Q
platelet granule release is mediated by what two molecules? what is the result?
A
- ADP
- TXA2
- result: exposure of fibrinogen receptors on platelet surface
9
Q
what characterizes the aggregation phase of platelet plug formation?
A
fibrinogen crosslinking between platelets via GpIIb
10
Q
all clotting factors are synthesized in the liver with the exception of:
A
- VIII
- vWF (cofactor VIII)
these are synthesized in the endothelium
11
Q
what is responsible for degrading Va and VIIIa?
A
protein C (with cofactor S)
12
Q
what is the single best test to evaluate liver function?
A
PT
13
Q
how do the extrinsic and intrinsic pathways differ?
A
- extrinsic: release of TF from damage OUTSIDE the blood vessel
- intrinsic: injury to the blood vessel with release of clotting factors from circulation
14
Q
the final common pathway results in:
A
conversion of fibrinogen to fibrin, and fibrin crosslinking
15
Q
plasminogen is converted to ____________ by _________ / __________ / ___________
A
- plasmin
- TPA / urokinase / streptokinase
16
Q
what is the primary signal of fibrinolysis?
A
TPA from endothelium
17
Q
plasmin cleaves ____________, leaving ______________
A
- fibrin
- E and D fragments (D-dimer)
18
Q
what are the inhibitors of fibrinolysis?
A
- primary: a2 antiplasmin (bound to fibrin, rapid acting)
- secondary: a2 microglobulin
19
Q
what are the anti-fibrinolysis meds?
A
- amicar
- aprotinin
- TXA
20
Q
what is the MOA of the anti-fibrinolysis drugs amicar and aprotinin?
A
block plasmin and kallikrein
21
Q
what is the MOA of the anti-fibrinolysis drug TXA?
A
lysine analog, blocks lysine receptors on plasminogen, more powerful than amicar
22
Q
antithrombin 3 binds and inactivates what factors?
A
- thrombin
- IX
- X
- XI
23
Q
how does heparin work?
A
induces conformational change in antithrombin 3, increasing reaction rate 1000x (for inactivation of II, IX, X, XI)
24
Q
what is the inheritance of antithrombin 3 deficiency?
A
AR
25
what is the clinical presentation of antithrombin 3 deficiency?
- 20-50 yo
- widespread DVT and arterial thrombosis
- pt appears resistant to heparin
26
what is the treatment for antithrombin 3 deficiency?
- FFP (replenishes AT3)
| - lifelong anticoagulation
27
less than ___% normal level of protein C/S leads to hypercoagulable state
less than 60%
28
what is the inheritance of protein C/S deficiency?
AR
29
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
30
what is the inheritance of factor V leiden?
AR
31
what is the pathogenesis of acquired hypercoagulable state?
liver failure can lose AT3 and have a picture like AT3 deficiency
32
what do the blood studies show in vWF disease?
- normal platelet count
| - slightly prolonged PTT
33
hemophilia A = factor _____ deficiency
VIII
34
what is the inheritance of hemophilia A?
X-linked
35
what are the blood labs for hemophilia A?
- increased PTT
| * obtain factor assay
36
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
37
hemophilia B = factor ____ deficiency
IX
38
what is the inheritance of hemophilia B?
X-linked
39
what do blood labs show for hemophilia B?
increased PTT
*obtain factor assay
40
what is the treatment for hemophilia B?
- cryoprecipitate, dose daily
| - need 50% activity for major surgery
41
which is worse - type 1 or 2 HIT?
type II
42
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
43
"white clots" on pathology is indicative of:
HIT
44
how is HIT diagnosed?
14C serotonin release assay / ELISA
*look for platelet clumping in presence of therapeutic heparin dosing
45
what is the treatment for HIT?
- stop heparin
| - use direct thrombin inhibitor (lepirudin, argatroban, coumadin) in setting of thrombosis
46
what are some direct thrombin inhibitors?
- lepirudin
- argatroban
- coumadin
47
what do the blood labs show with DIC?
- decreased platelets
- fibrinogen
- increased fibrin split products
- increased PT and PTT
48
what is the treatment for DIC?
- treat underlying cause
| - give platelets, FFP, cryoprecipitate
49
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
50
1 unit of pRBC should raise HCT by ___% in a 70kg person
2-4%
51
what is the shelf life of pRBC?
42 days
52
what is the best blood product option to improve O2 capacity without hypervolemia?
pRBC
53
how long can platelets be stored for?
5d
54
when is a platelet transfusion indicated?
platelet count under 100k or 50k in patients requiring surgery
55
______thermia (hypo/hyper) makes platelets unable to produce TXA2
hypothermia
56
_____ mL/kg FFP should replete coagulation factors to levels required for hemostasis?
10-15 mL/kg
57
FFP is stored at what temp?
-18C (to protect factors V, VIII)
58
does FFP require typing, crossmatch, both, or neither?
typing, but not crossmatch
59
what are the indications for FFP?
- coagulopathy of liver disease
- vitamin K deficiency
- coumadin therapy
- dilutional coagulopathy
- AT3 deficiency
60
what does cryoprecipitate contain?
- fibrinogen
- factor VIII
- vWF
- factor XIII
61
how is cryoprecipitate prepared?
plasma frozen to -90C, warmed slowly to 4C - precipitate which forms is separated with a small amount of plasma
62
what are the indications for cryoprecipitate?
- source of vWF in vWD
- source of factor VIII in hemophilia A
- source of fibrinogen in DIC
63
what is the presentation for febrile non-hemolytic transfusion reaction?
- isolated fever 1-6h after transfusion
- flank pain
- red/brown urine
64
what is the pathophysiology of febrile non-hemolytic transfusion reaction?
complement mediated destruction of transfused cell components by pre-existing antibodies
65
what is the treatment for febrile non-hemolytic transfusion reaction?
- acetaminophen
| - use buffy coat poor RBCs in the future
66
what is the presentation of hemolytic transfusion reaction?
- HA
- chest pain
- flank pain
- hemoglobinemia
- hemoglobinuria
- DIC
- acute renal failure
67
when does hemolytic transfusion reaction occur?
within first 50cc of blood
68
what is the treatment for hemolytic transfusion reaction?
- stop transfusion, recheck ABO
| - hydrate to UOP > 100cc/hr (mannitol, lasix, bicarb)
69
what is the pathophysiology of hemolytic transfusion reaction?
ABO incompatibility, personal errors
70
what is the pathophysiology of delayed hemolytic transfusion reaction? how does it present?
- minor blood group antigen incompatibility
| - days later: fever, chills, jaundice
71
what is the treatment for delayed hemolytic transfusion reaction?
hydrate to UOP > 100cc/hr (mannitol, lasix, bicarb)
72
what is the frequency of blood products as cause for TRALI?
FFP > PLT > RBC
73
what is the treatment for TRALI?
- supportive
- steroids
- AVOID DIURETICS
74
what does thromboelastograph (TEG) test?
coagulation profile
75
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
76
what does the R time indicate for the thromboelastograph (TEG) test?
initiation: time from initiation of test to initial pin movement / initial fibrin formation
77
what does a prolonged R time mean for thromboelastograph (TEG) test? what is the treatment?
factor deficiency - treat with FFP
78
what does the K value indicated for the thromboelastograph (TEG) test?
amplification: time to achieve clot strength, due to thrombin and platelet activation
79
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
80
what does a prolonged K / reduced alpha angle mean for the thromboelastograph (TEG) test? how is it treated?
fibrinogen deficiency - treat with cryoprecipitate
81
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
82
what does a reduced maximum amplitude mean for the thromboelastograph (TEG) test? how is it treated?
- thrombocytopenia
- platelet dysfunction
- treat with platelets or ddAVP
83
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
84
what does an elevated LY30 mean for the thromboelastograph (TEG) test? how is it treated?
rapid clot lysis - treat with TXA
85
what parameter represents the strongest point of fibrin clot and correlates with platelet function for the thromboelastograph (TEG) test?
maximum amplitude
86
what parameter determines the function of the maximum dynamic properties of fibrin and platelet bonding via GpIIb/IIIa for the thromboelastograph (TEG) test?
maximum amplitude
87
what parameter of the thromboelastograph (TEG) test gives a measure of degree of fibrinolysis?
clot lysis index (LY30)
88
if you suspect a fibrinogen deficiency what parameter(s) would you look at for the thromboelastograph (TEG) test?
K value and alpha angle
89
if you want to assess the rate of clot formation which parameter(s) would you look at for the thromboelastograph (TEG) test?
alpha angle
90
if you want to determine the time to achieve clot strength what parameter would you look at in the thromboelastograph (TEG) test?
K value
91
what is the half life of heparin?
dose dependent (45-150 min)
92
how is heparin removed from the body?
RES and kidneys
93
how is heparin function followed?
PTT (want 50-80s)
94
how is heparin reversed?
- protamine sulfate - give 1mg/100u heparin administered in preceding 2 hrs
- cross reacts with NPH insulin
95
what is the MOA of LMWH?
inhibits factor X over thrombin (4:1 ratio), with greater bioavailability
96
what are the advantages of LMWH?
- 2-4x longer half life
- excreted through kidney
- more predictable response to fixed doses
97
how do you measure LMWH activity?
anti-Xa assay
98
how is LMWH (Lovenox) reversed?
protamine sulfate: 1mg/mg Lovenox if given within 8 hrs; 0.5mg/mg Lovenox if over 8 hrs
99
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
100
what type of drug is fondaparinux (Aristra)? what is the route?
- selective Xa inhibitor
| - subQ
101
what are the indications for the selective factor Xa inhibitor fondaparinux (Aristra)?
- DVT proph
| - DVT/PE treatment
102
how is the selective factor Xa inhibitor fondaparinux (Aristra) cleared?
- hepatic (66%)
| - renal (33%)
103
how can selective factor Xa inhibitor (e.g. fondaparinux (Aristra)) activity be monitored?
anti-Xa activity
104
what is used to reverse selective factor Xa inhibitors fondaparinux (Aristra)?
Novoseven 90mc/kg (recombinant factor VII)
*no HD
105
what type of drugs are rivaroxaban (Xarelto) and apixaban (Eliquis)? what are the routes?
- selective factor Xa inhibitors
| - oral
106
what are the indications for rivaroxaban (Xarelto) and apixaban (Eliquis)?
- Afib
- DVT proph
- DVT/PE treatment
- ACS treatment
107
when are direct thrombin inhibitors used?
use in patients with heparin contraindications
108
how do direct thrombin inhibitors affect blood labs?
- all will increased PTT
| - must shoot for high INR if bridging to coumadin
109
what are the half lives of the direct thrombin inhibitors?
- lepirudin: 90 min
- bivalrudin: 25 min
- argatroban: 45 min
- dabigatran: 7-9 hr
110
what are the clearance routes for the direct thrombin inhibitors?
- lepirudin: renal
- bivalrudin: renal
- argatroban: hepatic
- dabigatran: renal
111
what are the routes for the direct thrombin inhibitors?
- lepirudin: IV/SC
- bivalrudin: IV
- argatroban: IV
- dabigatran: PO
112
how do you monitor the activity of direct thrombin inhibitors?
PTT (except for dabigatran - thrombin time)
113
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
114
what is the MOA of aspirin?
irreversibly inhibits COX; decreases prostacyclin and platelet thromboxane
115
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
116
what is the MOA for NSAIDs?
reversible COX inhibitors
117
what is the MOA of dipyridamole?
inhibits adenosine deaminase and phosphodiesterase, inhibits platelet aggregation
*dosed with ASA as aggrenox
118
what are the GpIIb/IIIa inhibitors?
- abciximab (Reopro)
- eptifibatide (Integrilin)
- tirofiban (Aggrastat)
119
- lepirudin
- bivalrudin
- argatroban
- dabigatran
are what type of drugs?
direct thrombin inhibitors
120
when are the GpIIb/IIIa agents used?
ACS / PCTA stenting
121
what is the half life of the GpIIb/IIIa agents?
0.5-1 hr
122
what is the MOA of ticlopidine and clopidogrel?
platelet aggregation inhibitors - irreversibly block binding of the ADP receptor
*stronger effect than ASA
123
how are the platelet aggregation inhibitors (ticlopidine and clopidogrel) metabolized?
cyp450
124
how long does it take for the platelet aggregation inhibitors (ticlopidine and clopidogrel) to start working?
3-5 days
125
how long before surgery should the platelet aggregation inhibitors (ticlopidine and clopidogrel) be held?
5 days
126
which of the platelet aggregation inhibitors (ticlopidine and clopidogrel) requires first pass liver metabolism?
Plavix (clopidogrel) - do not use in liver failure patients
127
what are the platelet aggregation inhibitors that block the p2y12 receptor for ADP?
- prasugrel (Effient)
- cangrelor (IV)
- ticagrelor (Brilinta, PO)
128
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
129
how does dextran work?
- thrombi undergo lysis at an increased rate
| - decreased platelet adhesion and aggregation
130
the platelet function assay depends on what factors?
- plasma vWF level
| - platelet number
131
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
132
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
133
what is indicated by prolongation of both col/EPI and col/ADP for PFA?
- anemia
- thrombocytopenia
- significant platelet dysfunction other than aspirin
