Lecture 6: Hemostasis Pharmacology & Transfusion Therapy Flashcards
1
Q
What are the major blood group systems?
A
ABO
Rh
2
Q
What antigens and antibodies does type A blood present with? O blood?
A
A blood presents with A antigens on its surface and anti-B antibodies in its plasma.
O blood presents with no antigens on its surface and anti-A and anti-B antibodies in its plasma.
3
Q
What kind of blood can O blood receive? AB? A?
A
O blood can receive O blood.
AB blood can receive A, B, AB, and O blood.
A blood can receive A and O blood.
4
Q
What is the difference between Rh+ and Rh-?
A
Rh+ has an antigen on its surface.
Rh- does not have an antigen on its surface.
5
Q
When does a rhesus hemolytic transfusion reaction occur?
A
Rh+ donor blood going to Rh- person for a second time.
6
Q
What are the pre-transfusion screenings done?
A
Type and Screen
Cross-match
7
Q
What is typing and what is screening?
A
Typing is determine blood phenoTYPE, aka ABO and Rh.
Screening is screening for antibodies that may react against other antigens.
8
Q
What is cross-matching?
A
Taking donor blood and mixing it with recipient blood.
9
Q
When do you order a cross-match?
A
Only if there is a high likelihood that a patient will receive PRBCs.
DO NOT ORDER IN EMERGENCY SETTING.
10
Q
What blood type is given in an emergency setting?
A
O- by default.
11
Q
What is the purpose of transfusion?
A
Replace acute blood loss
O2 delivery
Morbidity and mortality
12
Q
When is transfusion recommended barring exceptional circumstances?
A
Hgb < 6
13
Q
What are the transfusion recommendations based on in terms of patient condition?
A
Hemodynamically stable with no active bleed.
14
Q
How much Hb change does 1 unit of PRBCs do?
A
Increases Hb by 1g.
15
Q
What kind of consent does a blood transfusion require?
A
SIGNED informed consent. (for non-emergency)
16
Q
What are the most frequent reactions to being transfused?
A
Fever
Chills
Pruritis
Urticaria
17
Q
What should I do if a transfusion reaction occurs?
A
STOP and report to blood bank.
18
Q
What is the most common kind of transfusion reaction?
A
Febrile non-hemolytic reaction.
19
Q
What do you get from a blood donation? (Products)
A
Whole blood
PRBCs
FFP (fresh frozen plasma)
Cryoprecipitate
Platelets
20
Q
Why is whole blood rarely used?
A
Requires room temperature storage, which will degrade platelets and clotting factors if not used quickly.
21
Q
When is whole blood used?
A
Massive hemorrhage. It causes the highest oxygen affinity for the Hb.
22
Q
What is the volume of 1 unit of PRBCs?
A
200 mL usually.
23
Q
What are some modifications I can make to PRBCs?
A
Leukocyte reduced (Now universally performed anyways)
Irradiated
Washed
24
Q
What is the purpose of leukocyte reduced PRBCs?
A
Prevents immunologic responses or infectious transmission.
25
What is the purpose of irradiated PRBCs?
Avoid GVHD in immunodeficient people.
26
What is the purpose of washed PRBCs?
Prevent/eliminate complications associated with infusion of proteins present in residual concentrations.
27
What do you get from 1 unit of whole blood when separated?
1 unit of PRBCs
1 unit of platelets
1 unit of FFP
28
What blood product contains antibodies?
FFP
29
How does plasma transfusion differ from blood transfusion?
Opposite.
An AB blood person can receive donor AB plasma.
An O blood person can receive any donor plasma.
30
What is contained within FFP?
Coagulation factors
Fibrinogen
Antithrombin
Albumin
Protein C & S
31
What are the concerns when prepping an FFP transfusion?
24 hours once thawed to transfuse, otherwise F5 and F8 start to degrade.
32
Why is FFP the most used plasma product?
Contains all factors, so it can correct any deficiency.
33
What is cryoprecipitate?
Thawed FFP at 4C, collecting white precipitate rich in vWF, Factor 8, 13, and fibrinogen.
34
What is the key advantage of cryoprecipitate over FFP?
You can replace vWF, F8, F13, and fibrinogen using a much smaller volume than FFP.
35
What is factor concentrate?
A concentrate of a SPECIFIC factor made from either recombinant tech or THOUSANDS OF DONORS.
36
When do I use factor concentrate?
Only for very specific factor deficiencies, such as hemophilia A and B.
Minimal volume, no extraneous proteins.
37
What are the indications for platelet transfusion?
<10k to prevent spontaneous hemorrhage.
<50k in active bleeds, scheduled for invasive procedure, or qualitative intrinsic platelet disorder.
<100k in CNS injury, multisystem trauma, or neuro-surgery.
Normal count if ongoing active bleeding + platelet dysfunction dt congenital platelet disorder, chronic asa therapy, or uremia.
38
How much does a unit of platelets increase platelet count by?
5-10k.
39
What are the 4 hemostasis promoting agents?
Protamine sulfate
Vit K
Desmopressin
Thrombin
40
What is the indication for protamine sulfate?
HEPARIN REVERSAL AGENT.
41
What is the BBW of protamine sulfate?
Severe hypotensive or anaphylactoid reactions.
42
What is the indication and pharmaceutical name of Vitamin K?
Phytonadione or mephyton.
WARFARIN REVERSAL AGENT
43
What does vit K dosing depend on?
INR LEVEL
SEVERITY OF BLEEDING
44
How is Vit K metabolized?
HEPATIC
45
What is the indication for desmopressin/DDAVP?
Increase plasma levels of vWF, F8, and tPA, which reduces aPTT and bleeding time.
46
When administering desmopressin, what should I monitor?
Fluid Restriction
Sodium levels
47
What is the MOA and indication for topical thrombin?
MOA: Convert fibrinogen to fibrin at site of bleeding.
Indicated in surgery to aid in OOZING blood and minor bleeding only from CAPILLARIES and SMALL VENULES.
48
What is topical thrombin CI in?
Sensitive to things of bovine origin.
Massive bleed
NO LARGE VESSELS
49
What are the 3 categories of drugs that are antithrombotic?
Antiplatelet drugs
Anticoagulants drugs
Fibrinolytics
50
What is the purpose of an AC drug?
Prevent/treat clot/thrombus.
Generally indicated for venous thrombosis.
51
Which of the parental ACs is NOT renally cleared?
Unfrac heparin
Acova
52
What are the 3 general contraindications for parenteral ACs?
Bleeding (relative)
Renal function (except unfrac heparin)
Allergy
53
What are the parenteral ACs?
(Unfrac) heparin
LMWH
Bivalirudin/angiomax
Argatroban/Acova
54
How does heparin work?
Binds to anti-thrombin III, enhances its inactivation of F10a and thrombin.
55
How is heparin metabolized?
Hepatically
56
Is heparin preferred in pregnancy?
No.
LWMH is preferred.
57
Why does heparin need to be monitored?
It also binds to endothelium and plasma proteins, reducing AC effect.
58
How is heparin monitored?
aPTT or anti-F10 level.
59
What are the primary indications for heparin?
Prophylaxis of VT
DVT/PE
ACS
60
What are the adverse effects of heparin?
Bleeding
Thrombocytopenia
Osteoporosis
Elevated transminases
61
What are the caveats to osteoporosis and elevated transaminases in heparin?
Osteoporosis is only long-term (>1mo therapy)
Elevated LFTs is transient with no concomitant increase in bilirubin.
Returns to normal when heparin is stopped.
62
What is the #1 CI for heparin?
HIT!!!
Heparin induced thrombocytopenia
63
What are the CIs for heparin?
HIT
Allergy
Active Bleed
HEMOPHILIA
Significant thrombocytopenia
Purpura
Severe HTN
64
What is HIT?
A drug-induced thrombocytopenia.
Comes from heparin and PF4 forming neoantigen on PLT surface, causing a type 2 hypersensitivity reaction and plt clearance.
65
Why is HIT dangerous?
It can reduce platelet counts AND put pt in hypercoagulable state.
You can end up in HITT, which is HIT and thrombosis, which requires additional AC.
66
When does HIT occur?
ANY DOSE, ANY SCHEDULE, ANY ROUTE
Most common in UFH and females.
Most typical manifestation is thrombocytopenia.
67
When does HIT generally occur?
5-10 days post therapy INITIATION.
Early onset seen if recent heparin exposure.
68
Is venous or arterial thrombi more common in HIT?
Venous
69
What would cause us to suspect HIT?
New onset thrombocytopenia
50%+ drop in plt count from previous
Venous/arterial thrombosis
Necrotic skin lesions at injection site
Acute systemic reactions occurring after bolus.
70
How do we score HIT?
4Ts system. 0-2 pts per cat.
Thrombocytopenia
Timing of plt count fall
Thrombosis/other sequelae
Other causes
6 or more pts = extremely likely
71
What do we do if we suspect HIT?
STOP HEPARIN
Order HIPA, serotonin release assay, and Heparin-PF4 Ab ELISA
Switch to argatroban/angiomax if AC needed.
72
What should we always do in a patient's chart if they had HIT?
HEPARIN ALLERGY IN CHART.
73
What is the MOA of LWMH?
Enhance inhibition of F10 by AT 3 with LESS direct inhibition of F10 and no effect on thrombin.
Higher ratio of antiF10 to antiF2 compared to UFH.
74
What is nice about LWMH in terms of use?
SC in abd wall, so you can do it OP.
75
How is LWMH metabolized?
Renally cleared and metabolized. Adjust for renal impairment.
76
What are the indications for LWMH?
Same as UFH.
Prophylaxis of VT
DVT/PE
ACS
77
What condition CIs LWMH?
ESRD
78
What is the main difference in MOA between UFH and LWMH?
LMWH has a shorter molecule, which does NOT affect thrombin.
79
How is LWMH monitored?
Anti-F10 levels, since little effect on aPTT.
Generally not monitored unless preggo, CrCL <= 30, or morbid obesity.
80
What is preferred between LWMH and UFH?
LWMH
81
What drug is often used as bridging?
LWMH
82
What are the indications for bridging and when?
Bridging is done prior/post elective sx or invasive procedure for pts on warfarin:
Embolic stroke in 3 months
Previous embolic stroke or VTE during interruption of chronic AC
Mechanical valve
AFib in high stroke risk pt
83
What is argatroban(acova)?
NON-HEPARIN thrombin inhibitor
84
What is the MOA of argatroban (acova)?
Direct, highly-selective thrombin inhibitor.
Binds to the active thrombin site reversibly.
Inhibits fibrin formation, activation of F5, F8, and F13, protein C, and platelet aggregation.
85
How is argatroban(acova) metabolized?
Hepatically
86
How is argatroban monitored (acova)?
aPTT and LFTs
87
When is argatroban(acova) indicated?
PCI
ANY PT WITH HX OF HIT
88
Is argatroban (acova) safe in preggo?
Yes
89
What is angiomax?
Literally the same as argatroban in terms of class, MOA, onset.
90
How is angiomax different from argatroban (acova)?
RENAL CLEARANCE
Argatroban is hepatic.
(UFH and A is hepatic.)
91
Is angiomax safe in preggo?
No, because it is unknown.
92
What are the two main types of oral ACs?
Warfarin
DOACs
93
What is the MOA of warfarin?
Inhibit Vit K oxide reductase complex subunit 1, aka inhibits factor 2, 7, 9, 10 (all vit K dependent)
94
How is warfarin metabolized?
Liver
Sticks to albumin for a while.
95
How long does it take PT/INR to change from warfarin?
36-72 hrs.
96
When is warfarin absolutely CId?
PREGGO.
Cat D if mechanical heart valve, but still not preferred.
LWMH is preferred.
97
What is warfarin indicated for?
Prophylaxis and treatment of DVT/PE
Embolic complications from Afib or valve replacement.
98
What is the other adverse effect of warfarin besides bleeding?
Necrosis/gangrene, generally occurs if no initial therapy of LWMH or UFH.
99
What should you always do if RXing warfarin?
Drug interaction check.
Warfarin interacts with 745 drugs.
100
What are the main things to counsel pts about regarding warfarin use?
AVOID ALCOHOL
AVOID FOOD WITH LOTS OF VIT K
Vit E and cranberry juice increase warfarin effect.
Maintain a consistent diet and take it at the same time everyday.
101
What happens to a chronic alcoholic's PT/INR? Binge?
Chronic will have decreased PT/INR (less likely to bleed)
Binge will have increased PT/INR (more likely to bleed)
102
What are the DOACs and why do we love them?
Dabigatran/Pradaxa = thrombin inhibitor
Rivaroxaban/Xarelto = F10 inhibitor
Apixaban/Eliquis = F10 inhibitor
Edoxaban/Savaysa = F10 inhibitor
DOACs produce predictable levels of AC without changing your whole life and constant blood tests.
103
What is the indication for pradaxa?
Stroke prevention in non-valvular Afib, DVT/PE, DVT/PE prophylaxis post hip/knee sx.
Non-valvular means no mitral involvement.
104
When is pradaxa dosing adjusted?
Renal Impairment
CI in ESRD or HD.
105
What is the reversal agent for Pradaxa?
Praxbind
106
What are the indications for xarelto?
Same as pradaxa.
Stroke prevention in non-valvular Afib
DVT/PE
DVT/PE prophylaxis post hip/knee sx.
107
When is xarelto dosing adjusted?
CrCl < 50.
CI in ESRD/HD.
Relative CI in mod-severe hepatic impairment.
108
What are some counseling concerns for Xarelto Rxing?
NO GRAPEFRUIT JUICE
Avoid Ca++ blockers, arrhythmics, and fluoroquinolones.
109
What is the reversal agent for xarelto?
AndexXa
110
What are the indications for eliquis?
Same as xarelto.
111
When is eliquis dosing adjusted?
Renal impairment
112
What are some counseling concerns for eliquis Rxing?
NO GRAPEFRUIT JUICE
113
How is eliquis metabolized?
Hepatically.
114
What is the reversal agent for eliquis?
AndexXa
115
What are the indications for Savaysa?
Stroke prevention in non-valvular Afib
DVT/PE
116
When is Savaysa dosing adjusted?
Either in renal impairment OR for kidneys that are way too strong (>95 CrCl)
117
What is unique about Savaysa MOA?
Its inhibition of F10 does not require AT3.
118
How is Savaysa metabolized?
Hepatically
119
What is the reversal agent for Savaysa?
None.
120
Which of the DOACs is primarily renally excreted?
Pradaxa
121
Which of the DOACs has the best oral availability?
Xarelto
122
What is the preferred DOAC?
Eliquis,
Less risk of any major bleed compared to any other DOAC.
123
How is Heparin monitored and reversed?
aPTT
daily CBC
Protamine sulfate
124
How is warfarin monitored and reversed?
PT/INR
Vit K
125
How are DOACs monitored and reversed?
Kidney function.
Depends on DOAC.
126
What are the AP drugs?
ASA
Plavix
Prasugrel/Effient
Ticlopidine/Ticlid
Ticagrelor/Brilinta
Cangrelor/Kengreal
Eptifibatide/Integrilin
Abciximab/Reopro
127
What is MOA of ASA?
COX-1 inhibitor
IRREVERSIBLE BINDING
128
What competes with ASA?
NSAIDs.
ASA should be taken 60 mins before or 8 hrs post NSAID.
129
What are the indications for ASA?
Primary prophylaxis of MI
Secondary prevention with hx of vascular events or disease
130
What is the MOA of plavix?
Inhibition of ADP pathway, irreversibly blocking P2y12.
Requires metabolic activation
131
What are the indications of plavix?
Primary prophylaxis of MI
Standard prevention in pts with hx of vascular events.
132
What are some counseling tips for plavix?
Drugs that are 2C19 inhibitors will reduce plavix effectiveness.
Omeprazole and Esomeprazole.
133
What is the MOA of Effient/Prasugrel?
Irreversibly blocks P2Y12
Requires metabolic activation
Faster version of plavix
134
What is the CI for effient?
Hx of TIA or CVA
135
What is the MOA of Ticlopidine/Ticlid?
Irreversibly blocks P2Y12
136
What are the monitoring and SE concerns with Ticlopidine?
Life-threatening hematologic rxns.
Neutropenia
Agranulocytosis
TTP
Aplastic anemia
CBC w/diff q2weeks
137
What is the MOA of ticagrelor/brilinta?
REVERSIBLE and non-competitive binding of P2Y12
NO METABOLIC ACTIVATION
138
What is the common SE of Brilinta?
Dyspnea
139
What is the BBW of brilinta?
Reduced effectiveness if concomitant use of ASA > 100mg.
140
What is the MOA of Cangrelor/Kengreal?
REVERSIBLE and non-competitive binding of P2Y12.
141
What is Cangrelor/Kengreal indicated for?
PCI
It is IV only.
142
What is the MOA of eptifibatide/integrilin and abciximab/reopro? usage?
Gp 2b/2a receptor inhibitor.
Used for active PCI or high-risk pts with unstable angina.
143
What do fibrinolytics do and how are they deliver?
Used to breakdown thrombi in life-threatening situations.
Administered systemically or via catheter.
MOA is to convert plasminogen to plasmin, which degrades fibrin matrix.
144
What is the MOA of alteplase/tPA?
Preferential activation of bound plasminogen with fibrin.
Confines fibrinolysis to formed thrombus.
145
What is tPA indicated for?
IV for PE with hemodynamic INSTABILITY, acute STEMI, severe DVT, and ascending thrombophlebitis.
146
When can tPA be used for stroke?
Ischemic stroke approval if used with 3 hours of onset.
147
What is the MOA of streptokinase?
Converts inactive plasminogen to active plasmin.
Protein made by streptococci.
148
When is streptokinase CId?
ISCHEMIC STROKE
