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Pharm 2-EXAM #2 > Hematology 2 > Flashcards

Hematology 2 Flashcards

1
Q

Normal blood vessels contain

A

Endothelial cells

Nitric Oxide

Prostacyclin

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2
Q

Nitric oxide

A

Vasodilates

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3
Q

Prostacyclin prevents

A

PLT Activation & aggregation (keeps plug from growing too big)

Binds PLT receptors

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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

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5
Q

Primary hemostasis includes

A

Adhesion

Activation

Aggregation

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6
Q

Adhesion is the formation of a

A

PLT plug

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7
Q

During adhesion, endothelial cells are synthesize &

A

There is a release of Factor 8, which is von Willebrand factor

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8
Q

What is von Willebrand disease?

A

Despite normal PLT count & clot retraction, there is no adhesion of PLT & increased bleeding time

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9
Q

Patients with von Willebrand disease can be given

A

DDAVP

Cryoprecipitate

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10
Q

DDAVP, given pre-op, will release

A

Endogenous stores of vWF

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11
Q

Cryoprecipitate will give the patient what factors?

A

1, 8, & 13

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12
Q

Activation process involves

A

Thrombin

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13
Q

Factor ____ & _____ binds thrombin receptor on PLT

A

2 & 2a

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14
Q

The activation stage involves the synthesis & release of

A

Thromboxane A2

Adenosine Diphosphate (ADP)

Additional PLTs

Promotes aggregation

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15
Q

ADP is attacked by

A

Plavix

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16
Q

PLT aggregation involves

A

Thromboxane A2 uncovers fibrinogen receptors

Fibrinogen binds & links PLTs

Water-soluble & friable PLT plug forms (temporary hemostasis)

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17
Q

Secondary hemostasis will

A

Create a more stable clot

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18
Q

Secondary hemostasis involves

A

Fibrin production, which involves the coagulation cascade (intrinsic, extrinsic, & final common pathway)

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19
Q

Secondary hemostasis contains

A

ALL clotting factors

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20
Q

What are the characteristics of fibrin fibers?

A

Woven net over PLT plug

RBCs trapped

Cross-linked & water insoluble

STABLE CLOT

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21
Q

Fibrinogen is factor

A

1 (final common)

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22
Q

Prothrombin/thrombin is factor

A

2 (final common)

Vit K dependent

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23
Q

Tissue factor/thromboplastin is factor

A

3 (vascular wall & injured cells)

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24
Q

Calcium is factor

A

4

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25
Q

Proaccelerin is factor

A

5

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26
Q

Proconvertin is factor

A

7
Vit K dependent

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27
Q

Antihemophiliac is factor

A

8c

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28
Q

von Willebrand is factor

A

8 (vascular endothelial cells)

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29
Q

Christmas is factor

A

9
Vit K dependent

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30
Q

Stuart Power is factor

A

10
Vit K dependent

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31
Q

Plasma thromboplastin antecedent is factor

A

11

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32
Q

Hageman is factor

A

12

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33
Q

Fibrin stabilizing is factor

A

13

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34
Q

Protein c & s are

A

Vit K dependent

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35
Q

What are the 3 phases of cell based coagulation?

A

Initiation

Amplification

Propagation

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36
Q

Initiation involves what pathway?

A

Extrinsic

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37
Q

Characteristics of Extrinsic pathway

A

Low level initiation occurs in normal conditions

Outside vascular compartment

Tissue factor (Thromboplastin or Factor 3)-primary initiator of coagulation

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38
Q

What factors are included in the extrinsic pathway

A

3–>7a
(+4)–>
10

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39
Q

Amplification pathway is

A

Intrinsic

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40
Q

Thrombin is amplified by factors

A

7, 9 & 11

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41
Q

What factors are involved in the intrinsic pathway?

A

12–>11
|
8c<–9
(+4)–>10

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42
Q

Approaching the final common pathway is called

A

Propagation

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43
Q

9a is generated by tissue factor

A

7a & 11a

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44
Q

9a +8a on PLT surface + Ca (4)=

A

Responsible for 10c

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45
Q

What factors are involved in the final common pathway?

A

10–>5
(+4)
–>2
–>1
+13

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46
Q

Factor 13 causes

A

Covalent bonding, creating a water soluble & stable clot

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47
Q

PT (prothrombin time) will test which pathway?

A

Extrinsic

Final common

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48
Q

PT will detect

A

& diagnose bleeding or excessive clotting disorders

Monitor Anticoagulation therapy

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49
Q

What is a normal PT

A

11-14 seconds

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50
Q

What is a normal INR?

A

0.8-1.1

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51
Q

What happens due to a prolonged PT?

A

Decreases in factor 2, 5, 7, & 10 (prothrombin)

Hepatic dysfunction

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52
Q

Which medication will prolong PT?

A

Warfarin, which is a Vit K antagonist

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53
Q

Activated Partial Thromboplastin Time (aPTT) test which pathway?

A

Intrinsic & final common

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54
Q

aPTT will

A

Detect bleeding disorders & thrombotic episodes

Monitor anticoagulation therapy

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55
Q

What is a normal aPTT?

A

25-35 seconds

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56
Q

A prolonged aPTT can be due to

A

Hepatic dysfunction

Leukemia

Intrinsic coagulation factor

Vit K deficiencies

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57
Q

What medication can prolong aPTT?

A

Heparin therapy & other anticoagulants

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58
Q

Active clotting time (ACT) measures which pathway?

A

Intrinsic & final common

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59
Q

ACT monitors

A

Heparinization & protamine antagonization

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60
Q

What can prolong ACT?

A

Hypothermia

Thrombocytopenia

Contact activation inhibitors (aprotinin)

Factor 1, 12, or 7 deficiencies

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61
Q

Bleeding time should be

A

3-10 minutes

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62
Q

PLT count should be

A

150,00-400,000 cell/mL

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63
Q

Thrombin time should be

A

<30 seconds

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64
Q

Fibrinogen should be

A

> 150mg/dL

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65
Q

Thromboelastography & Thromboelastometry measures

A

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)

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66
Q

Anticoagulants

A

Decrease clotting

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67
Q

Naturally occurring heparin is release from

A

Mast cells during injury/inflammation

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68
Q

Heparin can be

A

Unfractionated (HMWH/LMWH)

Fractionated

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69
Q

What is the MOA of heparin?

A

Reversibly binds Antithrombin 3, increasing its activity 1,000-10,000 times

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70
Q

Heparin inhibits

A

Thrombin

Factor 10a, 12a, 11a, & 9a (7a, 2a)

PLT activation by fibrin

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71
Q

Onset of heparin IV? SC?

A

IV: immediate
SC: 1-2 hours

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72
Q

Heparin’s effectiveness is related to

A

Antithrombin 3 activity

Temperature

Protein binding

Individual response

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73
Q

Protein binding can cause

A

Heparin resistance

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74
Q

Dose fo heparin?

A

100units/kg IV initial bolus + 1,000 units/hr titrated to aPTT

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75
Q

What type of heparin should be used in PEDs?

A

Preservative free

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76
Q

What are characteristics of Heparin and pregnancy?

A

Lower plasma levels

Reduced efficacy

Monitor 10a

Doesn’t cross placenta

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77
Q

When performing neuraxial anesthesia, it is recommended to hold heparin for

A

> 4 hours

Neuraxial is avoided in coagulopathy

Low dose SubQ= no contraindication

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78
Q

What is the general rule for a patient on heparin & regional anesthesia?

A

No contraindications with low doses

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79
Q

When a patient is receiving heparin, you should monitor for

A

Neurological deficits (hematoma in epidural space)

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80
Q

Which lab values monitor heparin?

A

ACT

aPTT

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81
Q

Heparin blocks what pathways?

A

Intrinsic & Final

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82
Q

Heparin will prolong

A

ACT

aPTT

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83
Q

ACT goal for a patient on heparin

A

> 350-400 seconds

84
Q

aPTT goal rage for a patient on heparin

A

1.5-2.5x normal

85
Q

What is Heparin-Induced Thrombocytopenia? (HIT)

A

Formation of heparin-dependent antibodies to PLT factor 4

86
Q

With HIT, these 3 things can form

A

PLT activation + aggregation

Arterial & venous thrombosis

Preformed antibodies may cause subsequent allergic redaction to heparin

87
Q

Severe thrombocytopenia is

A

A 50% decrease or <100,000

May occur within hours of heparin exposure

Severe reaction within 4-5 days

88
Q

With low-molecular weight heparin, there is a greater

A

Inhibition of Factor 10a than thrombin (2a)

89
Q

With LMWH, there is less ________, which means there is a greater predictability in the dose response curve

A

Protein binding

90
Q

LMWH will peak in

91
Q

Monitor this when patient receives LMWH

A

10a levels

92
Q

What does NOT neutralize LMWH?

A

Protamine (unpredictable response)

93
Q

How long is LMWH held prior to surgery?

A

Held for 12 hours

94
Q

What is the risk of a patient receiving LMWH?

A

Risk of spinal & epidural hematoma

95
Q

Delay PNB/neuraxial _______ hrs following prophylaxis

_______hrs for therapeutic

A

10-12 hrs

24 hrs

96
Q

Warfarin is considered a

A

Vit K antagonist

Vit K epoxide reductase converts vit K-dependent coagulation proteins to active form

97
Q

Warfarin inhibits synthesis of which factors?

A

2 (prothrombin)
7
9
10

98
Q

Warfarin has a delayed onset of ____

Delayed peak of ______

Dose ______

A

8-12 hrs

36-72 hrs

2-10mg (variable)

99
Q

Does warfarin cross the placenta?

100
Q

What lab values should you monitor when receiving warfarin?

A

PT (sensitive to prothrombin 2, 7, & 10)

INR (anticoagulation target 2.0-3.0)

101
Q

What should be evaluated the day of surgery when a patient is on Warfarin?

102
Q

How many days should Warfarin be discontinued preoperative

103
Q

What is the reversal of Warfarin?

A

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
Q

What is the immediate reversal of Warfarin?

A

Prothrombin Complex Concentrate

105
Q

What medication is a synthetic anticoagulant & inhibits factor 10a INDIRECTLY?

A

Fondaparinux (Arixtra)- given SUBQ

106
Q

What is the alternate to heparin if a patient experiences HIT?

A

Fondaparinux (Arixtra), a synthetic anticoagulant

107
Q

Fondaparinux (Arixtra), a synthetic anticoagulant should be held for _____ prior to surgery

108
Q

What are DIRECT Thrombin Inhibitors? (IV/Parenteral)

A

Bivalirudin

Argatroban

109
Q

What are the characteristics of Bivalirudin, an IV DIRECT Thrombin Inhibitor?

A

High Affinity & specificity for binding thrombin

Monitor ACT

Hold 4-6 hrs before surgery

110
Q

What are the characteristics of Argatroban, an IV DIRECT Thrombin Inhibitor?

A

Less affinity & specificity for binding thrombin

Monitor aPTT & ACT

Hold 4-6 hrs before surgery

111
Q

What drug is a DIRECT Thrombin PO inhibitor?

A

Dabigatran Etexilate (Pradaxa)

112
Q

What should be monitor for a patient receiving Dabigatran Etexilate (Pradaxa), a DIRECT Thrombin PO inhibitor?

A

Monitor Thrombin Time

aPTT

113
Q

What are DIRECT FACTOR 10a Inhibitors?

A

Rivaroxaban (Xarelto)

Apixaban

114
Q

Direct Factor 10a Inhibitors, Rivaroxaban (Xarelto) & Apixaban, inhibit

A

Free, clot bound, & prothrombinase complex bound 10a

115
Q

How long should the direct factor 10a inhibitor Rivaroxaban (Xarelto) be held?

A

1-2 days before surgery (3 days for regional)

116
Q

How long should the direct factor 10a inhibitor, Apixaban be held?

A

3-5 days before regional/neuraxial

117
Q

Aspirin is a _________ & is a ________ inhibitor

A

Acetylsalicylic acid & non-steroid anti-inflammatory drug

PLT inhibitor

118
Q

What is the MOA of Aspirin?

A

IRREVERSIBLE acetylation of cyclooxygenase

Inhibits both isozyme forms (COX 1> COX-2)

119
Q

Cyclooxygenase produces

A

Pro-inflammatory prostaglandins & pro-clotting thromboxanes

120
Q

Aspirin prevents formation of

A

Thromboxane A2

121
Q

Aspirin lasts for

A

The life of the PLT, 7-10 days

122
Q

Clopidogrel (Plavix), is a

A

Prodrug (active metabolite)

123
Q

Clopidogrel (Plavix) MOA

A

Irreversible binding to P2Y-12 receptor

Inhibits ADP binding for PLT activation & aggregation

124
Q

When should Clopidogrel (Plavix) be discontinued?

A

5-7 days before surgery & regional anesthesia

125
Q

When a patient is on Clopidogrel, when should medication/surgery be delayed?

A

1 year after PCI with DES + Plavix therapy

1 month after BMS

126
Q

Thrombolytic agents are

A

Plasminogen activators

127
Q

Plaasaminogen activators (thrrombolytic agents) convert

A

Plasminogen to plasmin (fibrinolytic enzyme), which helps break down aa clot (clot lysis)

128
Q

What are examples of drug names that are thrombolytic agents

A

Streptokinase

Urokinase

Tissue Plasminogen Activator (tPA)

129
Q

What are the side effects & risk of thrombolytic agents

A

Intracranial Hemorrhage

Hemorrhage in trauma, surgery or invasive procedures

Angioedema

130
Q

When are thrombolytics contraindicated?

A

Within a minimum of 2 days or neuraxial/regional & surgery

131
Q

When a patient has been on thrombolytic agents, how often should you assess for neurological deficits?

132
Q

Activated Antithrombin 3 binds

A

Factor 2a (thrombin) & 10a

Partial inhibition of factors 9, 11 & 12

Forms complexes

133
Q

Antithrombin 3 removes

A

Clotting factors from circulation & neutralizes intrinsic & final common pathway

134
Q

What is required for Heparin

A

Co-factor Antithrombin 3

135
Q

What is considered to causes Antithrombin 3 deficiency?

A

Cirrhosis

Nephrotic syndrome

136
Q

Plasminogen is the

A

Inactive form of plasmin in the anti-coagulation pathway

137
Q

Plasminogen mixes

A

Into thrombin (a clot) during formation

138
Q

tPA is synthesized by

A

Endothelial cells

139
Q

tPA is released into circulation & is

A

Stimulated by thrombin & venous stasis

140
Q

tPA converts

A

plasminogen to plasmin

141
Q

uPA & streptokinase are

A

Plasminogen activators

142
Q

Plasmin breaks down

A

Fibrin= Fibrinolysis

Fibrin split

Maintains vascular potency

143
Q

Protein C is activated by

A

Thrombin-thrombomodulin complex

144
Q

Bound thrombin has

A

No procoagulant property

145
Q

Protein C regulates___________, has ________ properties, & binds _______

A

Regulates Anti-coagulation

Anti-inflammatory properties

Binds Protein s

146
Q

Protein S binds________

A

Binds Factor 5a & 8a, which are co-factors for thrombin

147
Q

Protein S compromises

A

Complex formation

148
Q

Procoagulants are drugs that

A

Reduce Bleeding

149
Q

Antifibrinolytics are used primarily in

A

Orthopedic cases

150
Q

Epsilon Aminocaproic Acid (EACA, AMICAR), a procoagulant & anti-fibrinolytic…

A

Enhances the formation of a stable clot

151
Q

What is the MOA of Epsilon Aminocaproic Acid (EACA, AMICAR), a procoagulant & anti-fibrinolytic?

A

Competitive inhibition of plasminogen to plasmin

152
Q

Epsilon Aminocaproic Acid (EACA, AMICAR), a procoagulant & anti-fibrinolytic will reduce the need for

A

RBC transfusion

153
Q

Tranexamic Acid (TXA) is a synthetic anti-fibrinolytic that

A

Enhances the formation of a stable clot

Reduces need for RBC transfusion

154
Q

What is the MOA of Tranexamic Acid (TXA)?

A

Competitive inhibition of plasminogen to plasmin

High doses will cause a DIRECT inhibition of plasmin

155
Q

TXA is _______ than EACA

A

10x more potent

156
Q

Topically applied TXA will have

A

A local effect with minimal systemic effects

157
Q

What is the safety concern of TXA?

A

Seizure risk (4mg)

GABA receptor blockade in frontal cortex

158
Q

Aprotinin is an anti-fibrinolytic that

A

Inhibits plasmin

159
Q

With Aprotinin, there is a risk of

A

Thrombus formation & mortality

160
Q

What are adverse effects of Anti-fibrinolytics?

A

Thrombus

Higher risk with Aprotinin

Wrong site

161
Q

When are Anti-fibriniolytics contraindicated?

A

Known hyper coagulable condition

Vascular anastomosis

DIC

Seizure (4mg)-high dose TXA

Renal dysfunction (EACA)

162
Q

What are symptoms of wrong site administration of Anti-fibrinolytics?

A

Back & leg pain

Myoclonus & seizures

HTN

Tachycardia

VF

Mortality of 50%

163
Q

Protamine inactivates

A

Acidic heparin molecules

Acid base neutralization

164
Q

Protamine inhibits

A

PLT & serine proteases involved in coagulation

165
Q

Dose of Protamine

A

1mg of protamine inactivates 100 units of heparin

166
Q

What happens with multiple administrations of Protamine?

A

Risk for heparin rebound after 2-3 doses

Risk for coagulopathy 7 PLT dysfunction

167
Q

What are side effects of Protamine?

A

HOTN

Anaphylaxis

Acute pulmonary vasoconstriction

Right ventricular failure

Increased risk in patients using NPH INSULIN

168
Q

Desmopressin (DDAVP) is an

A

Analogue of vasopressin

169
Q

Desmopressin (DDAVP) releases

A

Endogenous stores of mono Willebrand factor 8 from endothelial cells

170
Q

Giving Desmopressin (DDAVP) can treat

A

vW disease by shortening bleeding time & PTT

171
Q

What is the dose (administration) of DDAVP?

A

0.3mg/kg IV infusion over 15-30 minutes

172
Q

DDAVP administration will cause PLT adhesion

A

Within 30 minutes

173
Q

What is the duration of DDAVP?

174
Q

What are the risk of administration with DDAVP administration?

A

HOTN with rapid administration

Hyponatremia (PEDS)

175
Q

Fibrinogen (Factor 1) is involved in a

A

Stable clot formationo

176
Q

Fibrinogen (Factor 1) is an __________ for _________

A

Enzyme substrate for thrombin, factor 13a & plasmin

177
Q

Fibrinogen (factor 1) will bind

A

PLT receptors (GP 2b/3a) responsible for aggregation

178
Q

Fibrinogen loss can be due to

A

Hemorrhage

Hemodilution

Decreases clot stability

179
Q

What is a normal Fibrinogen (factor 1) level?

A

200-400mg/dL

180
Q

Low levels of fibrinogen (factor 1) may

A

Increase PT & PTT

181
Q

What is the typical replacement recommendation for fibrinogen (factor 1)?

A

Replace levels below 100-150mg/dL

182
Q

What is the treatment for low fibrinogen (factor 1) ?

A

Cryoprecipitate 1 unit/10kg (increases by 50-70mg/dL)

Fibrinogen concentrate

183
Q

Recombinant activated factor 7a (rFVIIa), a recombinant protein, can help

A

Manage bleeding in hemophilia

Life threatening hemorrhage

Cardiac surgery

184
Q

Recombinant activated factor 7a (rFVIIa), a recombinant protein, forms

A

Complex with tissue factor–> thrombin

185
Q

Recombinant activated factor 7a (rFVIIa), a recombinant protein, may normalize

A

PT/INR without correcting coagulation defect

186
Q

The recombinant protein, Factor 13 & recombinant factor 13, is involved in

A

The final common pathway of stabilizing a fibrin clot

187
Q

The recombinant protein, Factor 13 & recombinant factor 13, can help reduce

A

Postoperative hemorrhage & transfusion requirements

188
Q

The recombinant protein, prothrombin complex concentrate, involves which factors?

189
Q

The recombinant protein, prothrombin complex concentrate, helps manage

A

Bleeding in hemophilia B

190
Q

The recombinant protein, prothrombin complex concentrate, is used to treat

A

Warfarin reversal

Increased INR with life threatening bleeding

191
Q

Topical hemostatic agents like fibrin sealants, combine

A

Thrombin & Fibrinogen

192
Q

Topical agents should NOT

A

Be used near nerves or in confined spaces

193
Q

What substance anchors PLT to sub endothelial collagen?

A

Factor 8 (vW)

194
Q

What clotting factor activates the PLT at the site of injury?

195
Q

What 2 substances, which are released from the activated PLT, stimulates PLT aggregation?

A

Thromboxane A2

ADP

196
Q

Which factor is the primary INHIBITOR of the coagulation cascade

A

Factor 3 (tissue factor)

197
Q

Which factor is responsible for cross-linking of fibrin clot?

198
Q

Cryoprecipitate is most rich in what 3 coagulation factors?

199
Q

Antithrombin 3 primarily neutralizes which pathway & strongly inhibits which 2 coagulation factors?

A

Intrinsic & final common

2 & 10

200
Q

How does heparin work?

A

Intrinsic pathway

Increases activity of antithrombin 3

201
Q

How does Coumadin work?

A

Inhibits Vit K dependent factors 2, 7, 9 & 10

202
Q

What agents inhibit PLT aggregation by impairing cycle-oxygenase?

A

Aspirin (NSAID)

203
Q

Formation of which other PLT aggregator is blocked?

A

Thromboxane A2

204
Q

Which anti-PLT agent prevents ADP-induced PLT aggregation?

A

Clopidogrel (Plavix)

205
Q

Your patient with von Willebrand disease has not responded to desmopressin (DDAVP). What should you try next?

A

Cryoprecipitate

206
Q

How does protamine work?

A

Acid base neutralizer through heparin binding

207
Q

How does tranexamic acid work?

A

Inhibits plasminogen to plasmin

Pharm 2-EXAM #2 (5 decks)

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