Hematology 2 Flashcards
(207 cards)
1
Q
Normal blood vessels contain
A
Endothelial cells
Nitric Oxide
Prostacyclin
2
Q
Nitric oxide
A
Vasodilates
3
Q
Prostacyclin prevents
A
PLT Activation & aggregation (keeps plug from growing too big)
Binds PLT receptors
4
Q
What happens when a blood vessel is injured?
A
Connective tissue & collagen is exposed
PLT adhere & rupture
Serotonin is released, a potent local vasoconstrictor
PLT plug & blood clot is created
5
Q
Primary hemostasis includes
A
Adhesion
Activation
Aggregation
6
Q
Adhesion is the formation of a
A
PLT plug
7
Q
During adhesion, endothelial cells are synthesize &
A
There is a release of Factor 8, which is von Willebrand factor
8
Q
What is von Willebrand disease?
A
Despite normal PLT count & clot retraction, there is no adhesion of PLT & increased bleeding time
9
Q
Patients with von Willebrand disease can be given
A
DDAVP
Cryoprecipitate
10
Q
DDAVP, given pre-op, will release
A
Endogenous stores of vWF
11
Q
Cryoprecipitate will give the patient what factors?
A
1, 8, & 13
12
Q
Activation process involves
A
Thrombin
13
Q
Factor ____ & _____ binds thrombin receptor on PLT
A
2 & 2a
14
Q
The activation stage involves the synthesis & release of
A
Thromboxane A2
Adenosine Diphosphate (ADP)
Additional PLTs
Promotes aggregation
15
Q
ADP is attacked by
A
Plavix
16
Q
PLT aggregation involves
A
Thromboxane A2 uncovers fibrinogen receptors
Fibrinogen binds & links PLTs
Water-soluble & friable PLT plug forms (temporary hemostasis)
17
Q
Secondary hemostasis will
A
Create a more stable clot
18
Q
Secondary hemostasis involves
A
Fibrin production, which involves the coagulation cascade (intrinsic, extrinsic, & final common pathway)
19
Q
Secondary hemostasis contains
A
ALL clotting factors
20
Q
What are the characteristics of fibrin fibers?
A
Woven net over PLT plug
RBCs trapped
Cross-linked & water insoluble
STABLE CLOT
21
Q
Fibrinogen is factor
A
1 (final common)
22
Q
Prothrombin/thrombin is factor
A
2 (final common)
Vit K dependent
23
Q
Tissue factor/thromboplastin is factor
A
3 (vascular wall & injured cells)
24
Q
Calcium is factor
A
4
25
Proaccelerin is factor
5
26
Proconvertin is factor
7
Vit K dependent
27
Antihemophiliac is factor
8c
28
von Willebrand is factor
8 (vascular endothelial cells)
29
Christmas is factor
9
Vit K dependent
30
Stuart Power is factor
10
Vit K dependent
31
Plasma thromboplastin antecedent is factor
11
32
Hageman is factor
12
33
Fibrin stabilizing is factor
13
34
Protein c & s are
Vit K dependent
35
What are the 3 phases of cell based coagulation?
Initiation
Amplification
Propagation
36
Initiation involves what pathway?
Extrinsic
37
Characteristics of Extrinsic pathway
Low level initiation occurs in normal conditions
Outside vascular compartment
Tissue factor (Thromboplastin or Factor 3)-primary initiator of coagulation
38
What factors are included in the extrinsic pathway
3-->7a
(+4)-->
10
39
Amplification pathway is
Intrinsic
40
Thrombin is amplified by factors
7, 9 & 11
41
What factors are involved in the intrinsic pathway?
12-->11
|
8c<--9
(+4)-->10
42
Approaching the final common pathway is called
Propagation
43
9a is generated by tissue factor
7a & 11a
44
9a +8a on PLT surface + Ca (4)=
Responsible for 10c
45
What factors are involved in the final common pathway?
10-->5
(+4)
-->2
-->1
+13
46
Factor 13 causes
Covalent bonding, creating a water soluble & stable clot
47
PT (prothrombin time) will test which pathway?
Extrinsic
Final common
48
PT will detect
& diagnose bleeding or excessive clotting disorders
Monitor Anticoagulation therapy
49
What is a normal PT
11-14 seconds
50
What is a normal INR?
0.8-1.1
51
What happens due to a prolonged PT?
Decreases in factor 2, 5, 7, & 10 (prothrombin)
Hepatic dysfunction
52
Which medication will prolong PT?
Warfarin, which is a Vit K antagonist
53
Activated Partial Thromboplastin Time (aPTT) test which pathway?
Intrinsic & final common
54
aPTT will
Detect bleeding disorders & thrombotic episodes
Monitor anticoagulation therapy
55
What is a normal aPTT?
25-35 seconds
56
A prolonged aPTT can be due to
Hepatic dysfunction
Leukemia
Intrinsic coagulation factor
Vit K deficiencies
57
What medication can prolong aPTT?
Heparin therapy & other anticoagulants
58
Active clotting time (ACT) measures which pathway?
Intrinsic & final common
59
ACT monitors
Heparinization & protamine antagonization
60
What can prolong ACT?
Hypothermia
Thrombocytopenia
Contact activation inhibitors (aprotinin)
Factor 1, 12, or 7 deficiencies
61
Bleeding time should be
3-10 minutes
62
PLT count should be
150,00-400,000 cell/mL
63
Thrombin time should be
<30 seconds
64
Fibrinogen should be
>150mg/dL
65
Thromboelastography & Thromboelastometry measures
Coagulation time (onset of clot)
Clot formation time (angle formation): rate of fibrin polymerization
MAX clot firmness (max clot strength)
Lysis time (diagnosis of premature clot lysis & hyperfibrinolysis)
66
Anticoagulants
Decrease clotting
67
Naturally occurring heparin is release from
Mast cells during injury/inflammation
68
Heparin can be
Unfractionated (HMWH/LMWH)
Fractionated
69
What is the MOA of heparin?
Reversibly binds Antithrombin 3, increasing its activity 1,000-10,000 times
70
Heparin inhibits
Thrombin
Factor 10a, 12a, 11a, & 9a (7a, 2a)
PLT activation by fibrin
71
Onset of heparin IV? SC?
IV: immediate
SC: 1-2 hours
72
Heparin's effectiveness is related to
Antithrombin 3 activity
Temperature
Protein binding
Individual response
73
Protein binding can cause
Heparin resistance
74
Dose fo heparin?
100units/kg IV initial bolus + 1,000 units/hr titrated to aPTT
75
What type of heparin should be used in PEDs?
Preservative free
76
What are characteristics of Heparin and pregnancy?
Lower plasma levels
Reduced efficacy
Monitor 10a
Doesn't cross placenta
77
When performing neuraxial anesthesia, it is recommended to hold heparin for
>4 hours
Neuraxial is avoided in coagulopathy
Low dose SubQ= no contraindication
78
What is the general rule for a patient on heparin & regional anesthesia?
No contraindications with low doses
79
When a patient is receiving heparin, you should monitor for
Neurological deficits (hematoma in epidural space)
80
Which lab values monitor heparin?
ACT
aPTT
81
Heparin blocks what pathways?
Intrinsic & Final
82
Heparin will prolong
ACT
aPTT
83
ACT goal for a patient on heparin
>350-400 seconds
84
aPTT goal rage for a patient on heparin
1.5-2.5x normal
85
What is Heparin-Induced Thrombocytopenia? (HIT)
Formation of heparin-dependent antibodies to PLT factor 4
86
With HIT, these 3 things can form
PLT activation + aggregation
Arterial & venous thrombosis
Preformed antibodies may cause subsequent allergic redaction to heparin
87
Severe thrombocytopenia is
A 50% decrease or <100,000
May occur within hours of heparin exposure
Severe reaction within 4-5 days
88
With low-molecular weight heparin, there is a greater
Inhibition of Factor 10a than thrombin (2a)
89
With LMWH, there is less ________, which means there is a greater predictability in the dose response curve
Protein binding
90
LMWH will peak in
2-4 hours
91
Monitor this when patient receives LMWH
10a levels
92
What does NOT neutralize LMWH?
Protamine (unpredictable response)
93
How long is LMWH held prior to surgery?
Held for 12 hours
94
What is the risk of a patient receiving LMWH?
Risk of spinal & epidural hematoma
95
Delay PNB/neuraxial _______ hrs following prophylaxis
_______hrs for therapeutic
10-12 hrs
24 hrs
96
Warfarin is considered a
Vit K antagonist
Vit K epoxide reductase converts vit K-dependent coagulation proteins to active form
97
Warfarin inhibits synthesis of which factors?
2 (prothrombin)
7
9
10
98
Warfarin has a delayed onset of ____
Delayed peak of ______
Dose ______
8-12 hrs
36-72 hrs
2-10mg (variable)
99
Does warfarin cross the placenta?
YES
100
What lab values should you monitor when receiving warfarin?
PT (sensitive to prothrombin 2, 7, & 10)
INR (anticoagulation target 2.0-3.0)
101
What should be evaluated the day of surgery when a patient is on Warfarin?
INR
102
How many days should Warfarin be discontinued preoperative
3-5 days
103
What is the reversal of Warfarin?
FFP in emergent situation
Vit K-oral is preferred since it is more predictable; IV for severe episodes given slowly to avoid anaphylaxis (takes up to 24 hrs to work)
104
What is the immediate reversal of Warfarin?
Prothrombin Complex Concentrate
105
What medication is a synthetic anticoagulant & inhibits factor 10a INDIRECTLY?
Fondaparinux (Arixtra)- given SUBQ
106
What is the alternate to heparin if a patient experiences HIT?
Fondaparinux (Arixtra), a synthetic anticoagulant
107
Fondaparinux (Arixtra), a synthetic anticoagulant should be held for _____ prior to surgery
2+ days
108
What are DIRECT Thrombin Inhibitors? (IV/Parenteral)
Bivalirudin
Argatroban
109
What are the characteristics of Bivalirudin, an IV DIRECT Thrombin Inhibitor?
High Affinity & specificity for binding thrombin
Monitor ACT
Hold 4-6 hrs before surgery
110
What are the characteristics of Argatroban, an IV DIRECT Thrombin Inhibitor?
Less affinity & specificity for binding thrombin
Monitor aPTT & ACT
Hold 4-6 hrs before surgery
111
What drug is a DIRECT Thrombin PO inhibitor?
Dabigatran Etexilate (Pradaxa)
112
What should be monitor for a patient receiving Dabigatran Etexilate (Pradaxa), a DIRECT Thrombin PO inhibitor?
Monitor Thrombin Time
aPTT
113
What are DIRECT FACTOR 10a Inhibitors?
Rivaroxaban (Xarelto)
Apixaban
114
Direct Factor 10a Inhibitors, Rivaroxaban (Xarelto) & Apixaban, inhibit
Free, clot bound, & prothrombinase complex bound 10a
115
How long should the direct factor 10a inhibitor Rivaroxaban (Xarelto) be held?
1-2 days before surgery (3 days for regional)
116
How long should the direct factor 10a inhibitor, Apixaban be held?
3-5 days before regional/neuraxial
117
Aspirin is a _________ & is a ________ inhibitor
Acetylsalicylic acid & non-steroid anti-inflammatory drug
PLT inhibitor
118
What is the MOA of Aspirin?
IRREVERSIBLE acetylation of cyclooxygenase
Inhibits both isozyme forms (COX 1> COX-2)
119
Cyclooxygenase produces
Pro-inflammatory prostaglandins & pro-clotting thromboxanes
120
Aspirin prevents formation of
Thromboxane A2
121
Aspirin lasts for
The life of the PLT, 7-10 days
122
Clopidogrel (Plavix), is a
Prodrug (active metabolite)
123
Clopidogrel (Plavix) MOA
Irreversible binding to P2Y-12 receptor
Inhibits ADP binding for PLT activation & aggregation
124
When should Clopidogrel (Plavix) be discontinued?
5-7 days before surgery & regional anesthesia
125
When a patient is on Clopidogrel, when should medication/surgery be delayed?
1 year after PCI with DES + Plavix therapy
1 month after BMS
126
Thrombolytic agents are
Plasminogen activators
127
Plaasaminogen activators (thrrombolytic agents) convert
Plasminogen to plasmin (fibrinolytic enzyme), which helps break down aa clot (clot lysis)
128
What are examples of drug names that are thrombolytic agents
Streptokinase
Urokinase
Tissue Plasminogen Activator (tPA)
129
What are the side effects & risk of thrombolytic agents
Intracranial Hemorrhage
Hemorrhage in trauma, surgery or invasive procedures
Angioedema
130
When are thrombolytics contraindicated?
Within a minimum of 2 days or neuraxial/regional & surgery
131
When a patient has been on thrombolytic agents, how often should you assess for neurological deficits?
Q2H
132
Activated Antithrombin 3 binds
Factor 2a (thrombin) & 10a
Partial inhibition of factors 9, 11 & 12
Forms complexes
133
Antithrombin 3 removes
Clotting factors from circulation & neutralizes intrinsic & final common pathway
134
What is required for Heparin
Co-factor Antithrombin 3
135
What is considered to causes Antithrombin 3 deficiency?
Cirrhosis
Nephrotic syndrome
136
Plasminogen is the
Inactive form of plasmin in the anti-coagulation pathway
137
Plasminogen mixes
Into thrombin (a clot) during formation
138
tPA is synthesized by
Endothelial cells
139
tPA is released into circulation & is
Stimulated by thrombin & venous stasis
140
tPA converts
plasminogen to plasmin
141
uPA & streptokinase are
Plasminogen activators
142
Plasmin breaks down
Fibrin= Fibrinolysis
Fibrin split
Maintains vascular potency
143
Protein C is activated by
Thrombin-thrombomodulin complex
144
Bound thrombin has
No procoagulant property
145
Protein C regulates___________, has ________ properties, & binds _______
Regulates Anti-coagulation
Anti-inflammatory properties
Binds Protein s
146
Protein S binds________
Binds Factor 5a & 8a, which are co-factors for thrombin
147
Protein S compromises
Complex formation
148
Procoagulants are drugs that
Reduce Bleeding
149
Antifibrinolytics are used primarily in
Orthopedic cases
150
Epsilon Aminocaproic Acid (EACA, AMICAR), a procoagulant & anti-fibrinolytic...
Enhances the formation of a stable clot
151
What is the MOA of Epsilon Aminocaproic Acid (EACA, AMICAR), a procoagulant & anti-fibrinolytic?
Competitive inhibition of plasminogen to plasmin
152
Epsilon Aminocaproic Acid (EACA, AMICAR), a procoagulant & anti-fibrinolytic will reduce the need for
RBC transfusion
153
Tranexamic Acid (TXA) is a synthetic anti-fibrinolytic that
Enhances the formation of a stable clot
Reduces need for RBC transfusion
154
What is the MOA of Tranexamic Acid (TXA)?
Competitive inhibition of plasminogen to plasmin
High doses will cause a DIRECT inhibition of plasmin
155
TXA is _______ than EACA
10x more potent
156
Topically applied TXA will have
A local effect with minimal systemic effects
157
What is the safety concern of TXA?
Seizure risk (4mg)
GABA receptor blockade in frontal cortex
158
Aprotinin is an anti-fibrinolytic that
Inhibits plasmin
159
With Aprotinin, there is a risk of
Thrombus formation & mortality
160
What are adverse effects of Anti-fibrinolytics?
Thrombus
Higher risk with Aprotinin
Wrong site
161
When are Anti-fibriniolytics contraindicated?
Known hyper coagulable condition
Vascular anastomosis
DIC
Seizure (4mg)-high dose TXA
Renal dysfunction (EACA)
162
What are symptoms of wrong site administration of Anti-fibrinolytics?
Back & leg pain
Myoclonus & seizures
HTN
Tachycardia
VF
Mortality of 50%
163
Protamine inactivates
Acidic heparin molecules
Acid base neutralization
164
Protamine inhibits
PLT & serine proteases involved in coagulation
165
Dose of Protamine
1mg of protamine inactivates 100 units of heparin
166
What happens with multiple administrations of Protamine?
Risk for heparin rebound after 2-3 doses
Risk for coagulopathy 7 PLT dysfunction
167
What are side effects of Protamine?
HOTN
Anaphylaxis
Acute pulmonary vasoconstriction
Right ventricular failure
Increased risk in patients using NPH INSULIN
168
Desmopressin (DDAVP) is an
Analogue of vasopressin
169
Desmopressin (DDAVP) releases
Endogenous stores of mono Willebrand factor 8 from endothelial cells
170
Giving Desmopressin (DDAVP) can treat
vW disease by shortening bleeding time & PTT
171
What is the dose (administration) of DDAVP?
0.3mg/kg IV infusion over 15-30 minutes
172
DDAVP administration will cause PLT adhesion
Within 30 minutes
173
What is the duration of DDAVP?
4-6 hours
174
What are the risk of administration with DDAVP administration?
HOTN with rapid administration
Hyponatremia (PEDS)
175
Fibrinogen (Factor 1) is involved in a
Stable clot formationo
176
Fibrinogen (Factor 1) is an __________ for _________
Enzyme substrate for thrombin, factor 13a & plasmin
177
Fibrinogen (factor 1) will bind
PLT receptors (GP 2b/3a) responsible for aggregation
178
Fibrinogen loss can be due to
Hemorrhage
Hemodilution
Decreases clot stability
179
What is a normal Fibrinogen (factor 1) level?
200-400mg/dL
180
Low levels of fibrinogen (factor 1) may
Increase PT & PTT
181
What is the typical replacement recommendation for fibrinogen (factor 1)?
Replace levels below 100-150mg/dL
182
What is the treatment for low fibrinogen (factor 1) ?
Cryoprecipitate 1 unit/10kg (increases by 50-70mg/dL)
Fibrinogen concentrate
183
Recombinant activated factor 7a (rFVIIa), a recombinant protein, can help
Manage bleeding in hemophilia
Life threatening hemorrhage
Cardiac surgery
184
Recombinant activated factor 7a (rFVIIa), a recombinant protein, forms
Complex with tissue factor--> thrombin
185
Recombinant activated factor 7a (rFVIIa), a recombinant protein, may normalize
PT/INR without correcting coagulation defect
186
The recombinant protein, Factor 13 & recombinant factor 13, is involved in
The final common pathway of stabilizing a fibrin clot
187
The recombinant protein, Factor 13 & recombinant factor 13, can help reduce
Postoperative hemorrhage & transfusion requirements
188
The recombinant protein, prothrombin complex concentrate, involves which factors?
2
7
9
10
189
The recombinant protein, prothrombin complex concentrate, helps manage
Bleeding in hemophilia B
190
The recombinant protein, prothrombin complex concentrate, is used to treat
Warfarin reversal
Increased INR with life threatening bleeding
191
Topical hemostatic agents like fibrin sealants, combine
Thrombin & Fibrinogen
192
Topical agents should NOT
Be used near nerves or in confined spaces
193
What substance anchors PLT to sub endothelial collagen?
Factor 8 (vW)
194
What clotting factor activates the PLT at the site of injury?
Thrombin
195
What 2 substances, which are released from the activated PLT, stimulates PLT aggregation?
Thromboxane A2
ADP
196
Which factor is the primary INHIBITOR of the coagulation cascade
Factor 3 (tissue factor)
197
Which factor is responsible for cross-linking of fibrin clot?
Factor 13
198
Cryoprecipitate is most rich in what 3 coagulation factors?
1
8
13
199
Antithrombin 3 primarily neutralizes which pathway & strongly inhibits which 2 coagulation factors?
Intrinsic & final common
2 & 10
200
How does heparin work?
Intrinsic pathway
Increases activity of antithrombin 3
201
How does Coumadin work?
Inhibits Vit K dependent factors 2, 7, 9 & 10
202
What agents inhibit PLT aggregation by impairing cycle-oxygenase?
Aspirin (NSAID)
203
Formation of which other PLT aggregator is blocked?
Thromboxane A2
204
Which anti-PLT agent prevents ADP-induced PLT aggregation?
Clopidogrel (Plavix)
205
Your patient with von Willebrand disease has not responded to desmopressin (DDAVP). What should you try next?
Cryoprecipitate
206
How does protamine work?
Acid base neutralizer through heparin binding
207
How does tranexamic acid work?
Inhibits plasminogen to plasmin
