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Flashcards in Exsanguination Deck (133):
1

what are the four general steps of normal hemostasis?

1. capillary vasoconstriction
2. platelet plug formation
3. coagulation (fibrin formation)
4. fibrinolysis (occurs simultaneously)

2

what molecule is primarily responsible for the vasoconstriction and platelet aggregation during normal hemostasis? where is it released from?

- TXA2
- released from platelets

3

what molecule opposes TXA2 during normal hemostasis? where is it released from?

- prostacyclin
- released from endothelium

4

what is the lifespan of megakaryocytes?

8d

5

1/3 of megakaryocytes are sequestered in the __________

spleen

6

what are the 4 steps of platelet plug formation?

1. adherence
2. activation
3. granule release
4. aggregation

7

platelets adhere to subendothelial collagen at site of injury mediated by _______ and _________

vWF and GpIb

8

platelet granule release is mediated by what two molecules? what is the result?

- ADP
- TXA2

- result: exposure of fibrinogen receptors on platelet surface

9

what characterizes the aggregation phase of platelet plug formation?

fibrinogen crosslinking between platelets via GpIIb

10

all clotting factors are synthesized in the liver with the exception of:

- VIII
- vWF (cofactor VIII)

these are synthesized in the endothelium

11

what is responsible for degrading Va and VIIIa?

protein C (with cofactor S)

12

what is the single best test to evaluate liver function?

PT

13

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

14

the final common pathway results in:

conversion of fibrinogen to fibrin, and fibrin crosslinking

15

plasminogen is converted to ____________ by _________ / __________ / ___________

- plasmin
-TPA / urokinase / streptokinase

16

what is the primary signal of fibrinolysis?

TPA from endothelium

17

plasmin cleaves ____________, leaving ______________

- fibrin
- E and D fragments (D-dimer)

18

what are the inhibitors of fibrinolysis?

- primary: a2 antiplasmin (bound to fibrin, rapid acting)
- secondary: a2 microglobulin

19

what are the anti-fibrinolysis meds?

- amicar
- aprotinin
- TXA

20

what is the MOA of the anti-fibrinolysis drugs amicar and aprotinin?

block plasmin and kallikrein

21

what is the MOA of the anti-fibrinolysis drug TXA?

lysine analog, blocks lysine receptors on plasminogen, more powerful than amicar

22

antithrombin 3 binds and inactivates what factors?

- thrombin
- IX
- X
- XI

23

how does heparin work?

induces conformational change in antithrombin 3, increasing reaction rate 1000x (for inactivation of II, IX, X, XI)

24

what is the inheritance of antithrombin 3 deficiency?

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