Fiser.02.Hematology Flashcards
1
Q
What are the three initial responses to vascular injury?
A
Vascular vasoconstriction; platelet adhesion; thrombin generation
2
Q
Name the 5 steps of primary hemostasis
A
Platelet adhesion to exposed vWF;
Shape change;
Granule release with ADP and TXA2;
Recruitment of additional platelets;
Aggregation and formation of hemostatic plug
3
Q
Name the four initial substrates that start the “intrinsic pathway”
A
Exposed collagen, prekallikrein, HMW kininogen, factor XII
4
Q
Name the next 5 steps of the intrinsic pathway
A
Collagen, prekallikrein, HMW kinogen, factor XII –> activate factor XI Factor XI –> activates IX and add VIII IX + VIII –> activates factor X and add V X + V –> converts prothrombin (factor II) to thrombin Thrombin –> converts fibrinogen to fibrin
5
Q
What are the initial components that start the “extrinsic pathway”?
A
Tissue factor (from injured cells) and factor VII
6
Q
Name the three additional steps to the extrinsic coagulation cascade
A
Tissue factor + Factor VII –> activate X, add V X + V –> convert prothrombin (factor II) to thrombin Thrombin –> converts fibrinogen to fibrin
7
Q
Name the five components of the “prothrombin complex”
A
Factor X, factor V, Ca, platelet factor 3, prothrombin
8
Q
Where does the prothrombin complex form?
A
Forms on platelets
9
Q
What does the prothrombin complex do?
A
Catalyzes the formation of thrombin
10
Q
What is the convergence point for the intrinsic and extrinsic pathways?
A
Factor X
11
Q
What is the convergence point for the intrinsic and extrinsic pathways?
A
Factor X is common for both parts of the pathway
12
Q
What inhibits factor X?
A
Tissue factor pathway inhibitor
13
Q
What does fibrin do?
A
Links platelets together by binding GpIIb/IIIa molecules to form the platelet plug
14
Q
What does factor XIII do?
A
Helps crosslink fibrin
15
Q
Name three functions of thrombin
A
Converts fibrinogen –> fibrin + fibrin split products Activates factors V and VIII Activates platelets
16
Q
Which factor has the shortest half life
A
Factor VII
17
Q
Which two factors are considered labile b/c they have activity lost in stored blood but not in FFP?
A
V and VIII
18
Q
Which factor is the only one not synthesized in the liver? Where is it synthesized?
A
Factor VIII is synthesized in the endothelium
19
Q
Name 6 vitamin-K dependent factors
A
Factors II, VII, IX, X, Protein C, Protein S
20
Q
How long does it take for Vitamin K to have an effect?
A
Takes 6 hours
21
Q
How long does it take FFP to take effect
A
Immediate effect that lasts 6 hours
22
Q
What is the normal (in vivo) half life of RBCs?
A
120 days
23
Q
What is the normal (in vivo) half life of platelets?
A
7 days
24
Q
What is the normal (in vivo) half life of PMNs?
A
1-2 days
25
Where is prostacyclin (PGI2) synthesized?
Endothelium
26
Name 2 functions of prostacyclin (PGI2). What does it antagonize?
Decreases platelet aggregation; promotes vasodilation; antagonistic to TXA2 (thomboxane)
27
Where is thromboxane (TXA2) synthesized?
Platelets
28
Name two functions of TXA2
Increases platelet aggregation and promotes vasoconstriction
29
Name the underlying MOA of TXA2 function in platelet aggregation
TXA2 triggers release of calcium in platelets --\> exposes GpIIb/IIIa receptor GpIIb/IIIa receptor causes platelet-platelet binding Allows platelet-collagen binding with GpIb receptor
30
Name four functions of antithrombin III (AT III)
Key to anticoagulation: binds and inhibits thrombin, factor IX, X, and XI
31
How does heparin interact with AT-III and by how much does it increase its activity?
Consitutively activates AT-III up to 1000x normal activity
32
Name three effects of protein C
Degrades factor V, VIII, and fibrinogen
33
Name one effect of protein S
Protein C co-factor
34
Where is tissue plasminogen activator (TPA) synthesized and released from?
Endothelium
35
What does TPA do?
Converts plasminogen to plasmin
36
Name four effects of plasmin
Degrades factors V, VIII, fibrinogen, and fibrin Lose platelet plug
37
What does alpha-2 antiplasmin do and where is it released from?
Released from endothelium, natural inhibitor of plasmin
38
Which blood product has the highest levels of vWF-VIII?
Cryoprecipitate
39
Name two diseases that can be treated with cryoprecipitate and why
Von willebrand’s disease (for vWF) Hemophilia A (for factor VIII deficiency)
40
Does cryoprecipitate contain fibrinogen?
Yes, contains high levels of fibrinogen
41
What factors are in FFP?
All coagulation factors, protein C, protein S, and AT-III
42
How does DDAVP (desmopressin) affect the coagulation cascade?
Causes release of factor VIII and vWF from endothelium
43
How do conjugated estrogens affect the coagulation cascade?
Cause release of factor VIII and vWF from endothelium
44
What does PT measure in terms of coagulation cascade (5) and organ function?
Factor II, V, VII, X; fibrinogen Best for liver synthetic function
45
What does PTT measure and not measure?
Measures most factors + fibrinogen Does not measure factor VII and XIII – therefore cannot use for factor VII deficiency
46
What is your goal PTT for routine anticoagulation?
Goal PTT 60-90 seconds
47
What does ACT stand for?
Activated clotting time
48
What is your goal ACT for routine anticoagulation?
ACT 150-200 seconds
49
What is your goal ACT for cardiopulmonary bypass?
\> 460 seconds
50
What level INR is a relative CI for surgery?
INR \> 1.5
51
What level INR is a relative CI for CVL, percutaneous needle bx, or eye surgery?
INR \> 1.3
52
What is the MCC of surgical bleeding?
Incomplete hemostasis
53
What is the most common congenital bleeding disorders?
Von wilibrands disease
54
Which subtypes of vWD are autosomal dominant versus autosomal recessive?
Types I & II are AD, Type III is AR
55
What does vWF do in terms of coagulation?
Links the GpIb receptor on platelets to collagen
56
What is the coagulation test profile (PT/PTT/bleeding time) with von willebrands disease
PT normal; PTT normal/abnormal; prolonged bleeding time
57
What is another name for the bleeding time test?
Risocetin test
58
Which subtype of vWD is most common? What percentage of vWD does it encompasss?
70% of cases are Type I – mild symptoms
59
Which subtype of vWD causes the most severe symptoms?
Type III causes the most severe symptoms
60
What is the pathophysiology of type I vWD?
Reduced quantity of vWF
61
What is the treatment of type I vWD (3)?
Recombinant VIII:vWF, DDAVP, cryoprecipitate
62
What is the pathophysiology of type II vWD?
Defect in vWF molecule itself, therefore the vWF does not work well
63
What is the treatment of type II vWD (2)?
Recombinant VIII:vWF; cryoprecipitate
64
What is the pathophysiology of type III vWD?
Complete vWF deficiency (rare)
65
What is the treatment for type III vWD?
Recombinant VIII:vWF; cryoprecipitate DDAVP will not work
66
What is the underlying deficiency for Hemophilia A?
Factor VIII deficiency
67
How is hemophilia A inherited?
Sex-linked recessive
68
What factor VIII levels do you need preop for hemophilia A patients?
100% preop
69
What factor VIII levels do you need for 10-14 days after surgery for hemophilia A patients?
80-100%
70
What PT/PTT measurements do you see with hemophilia A patients?
Prolonged PTT, normal PT
71
Why may babies with hemophilia A not bleed at circumcision?
Because factor VIII crosses the placenta
72
How do you treat hemophiliac joint bleeding? What treatment is contraindicated?
Ice, mobility with ROM exercises, factor VIII concentrate or cryoprecipitate DO NOT ASPIRATE
73
What is the underlying cause of Hemophilia B?
Factor IX deficiency
74
What is the alternative name for Hemophilia B?
Christmas disease
75
How is Hemophilia B inherited?
Sex-linked recessive
76
What factor IX levels do you need preop for hemophilia B?
Need 100% preop
77
What factor IX levels do you need 2-3 days postop for hemophilia B?
30-40%
78
What PT/PTT levels do you see in hemophilia B?
Prolonged PTT, normal PT
79
How do you treat hemophilia B?
Recombinant factor IX or FFP
80
What PT/PTT levels do you see with factor VII deficiency?
Prolonged PT, normal PTT
81
How do you treat factor VII deficiency (2)?
Recombinant factor VII concentrate or FFP
82
What symptoms are associated with platelet disorders (5)?
Bruising, epistaxis, mucosal bleeding, petechiae, purpura
83
Name two causes of acquired thrombocytopenia
H2 blockers, heparin
84
What is the underlying pathophysiology of Glanzmann’s thrombocytopenia
Gp-IIb/IIIa receptor deficiency on platelets, so they cannot bind to each other; Gp Iib/IIIa receptors normally are cross-linked by fibrin
85
What is the treatment for Glanzmann’s thrombocytopenia?
Platelets
86
What is the underlying pathophysiology of Bernard Soulier disease
GpIb receptor deficiency on platelets so they cannot bind to collagen vWF normally linkds GpIb receptor on platelets to collagen
87
How do you treat Bernard Soulier disease?
Platelets
88
How does uremia affect coagulation?
Inhibits platelet function
89
How do you treat uremia-induced platelet dysfunction?
First line: hemodialysis Next: DDAVP, platelets
90
What is the pathophysiology of heparin-induced thrombocytopenia (HIT)?
Antiplatelet antibodies formed against heparin-platelet factor 4 complex which results in platelet destruction
91
What type of Ab is created in HIT
IgG PF4 antibody
92
What is the underlying pathophysiology and result of heparin-induced thrombocytopenia & thrombosis (HITT)?
Platelet aggregation and thrombosis resulting in a white clot
93
What medications cause HIT/HITT?
Low doses of heparin, can occur with low molecular weight heparin
94
Does LMWH have the same risk of causing HIT/HITT as heparin
No, LMWH has reduced risk of HIT/HITT
95
What is the treatment of HIT?
Stop heparin, start argatroban to anticoagulate
96
What is the MOA of argatroban
Direct thrombin inhibitor
97
What initiates the cascade of disseminated intravascular coagulation (DIC)?
Tissue factor
98
What are the lab findings with DIC (6)?
Decreased platelets, low fibrinogen, high fibrin split products, high D-dimer, prolonged PT, prolonged PTT
99
What is the treatment of DIC?
Treat underlying cause (ex: sepsis)
100
How many days preop should you stop aspirin?
Stop 7 days preop
101
How does ASA affect bleeding time?
Prolongs bleeding time
102
What is the MOA of ASA
Inhibits cyclooxygenase in platelets and decreases TXA2
103
Why is ASA’s effects on platelets irreversible?
Platelets lack DNA so they cannot resynthesize COX
104
How many days before surgeryshould you stop clopidogrel/Plavix?
Stop 7 days before surgery
105
What is the MOA of Plavix?
ADP-receptor antagnoist
106
How do you reverse Plavix?
Platelets
107
How many days before surgery should you stop coumadin? What can you bridge with?
Stop 7 days before surgery, consider bridging with heparin
108
What level of platelets do you want preop?
\>50K
109
What level of platelets do you want postop?
\>20K
110
How can prostate surgery affect coaguulation?
Releases urokinase, activates plasminogen thrombolysis
111
How do you treat this complication of prostate surgery?
Εaminocaproic acid (Amicar)
112
What is the best way to predict bleeding risk?
H&P
113
Why doesn’t a normal circumcision rule out bleeding disorders?
Because some factors cross the placenta
114
What two surgical history questions pick up 99% of patients with bleeding disorders?
History of excessive bleeding with tonsillectomy or wisdom tooth extraction
115
What are two common bleeding disorders that present with epistaxis?
vWF deficiency and platelet disorders
116
What gynecologic problem is common in patients with bleeding disorders?
Menorrhagia
117
How do hypercoaguable disorders usually present?
Venous or arterial thrombosis or emboli (DVT/PE/CVA)
118
What is the most common hypercoaguable disorder
Factor V Leiden mutation
119
What is the most common presenting symptom of Factor V Leiden mutation and in what % of patients?
30% of patients p/w spontaneous venous thromboses
120
What is the MOA of Factor V Ledien mutation?
Defect on factor V causing resistance to activated protein C
121
What is the treatment for Factor V Leiden mutation?
Heparin / warfarin
122
What is the treatment for hyperhomocysteinemia
Folic acid and B12
123
What is the treatment for prothrombin gene defect G20210A
Heparin / warfarin
124
What is the treatment for protein C or S deficiency?
Heparin / warfarin
125
What is a common comorbidity with antiphospholipid antibody syndrome?
SLE – although not all patients have this
126
What is the underlying pathophysiology of antiphospholipid antibody syndrome?
Antibodies to cardiolipin and lupus anticoagulant (phospholipids) This makes the patients hypercoaguable
127
What are three lab findings that are seen with antiphospholipid antibody syndrome?
Prolonged PTT despite hypercoaguable state, not corrected with FFP Positive Russel vipor venom time False-positive RPR test for syphilis
128
How do you treat antiphospholipid antibody syndrome?
Heparin / warfarin
129
What is the MCC of acquired hypercoaguability
Tobacco
130
Name 8 other causes of acquired hypercoaguability
Malignancy Inflammatory disease, IBD, rheumatoid arthritis Infections OCPs / pregnancy Myeloproliferative disorders
131
How does cardiopulmonary bypass result in a hypercoaguable state?
Factor XII (Hageman factor) activated
132
How do you prevent CPB-induced hypercoaguable state?
Heparin to prevent
133
Which patients are at risk for warfarin-induced skin necrosis?
Occurs when patients placed on coumadin without heparin bridge Patients with relative protein C deficiency are susceptible
134
What is the MOA of warfarin-induced skin necrosis?
Protein C and S decrease in levels due to their short half-lives compared to other procoagulation factors Results in hyperthrombotic state
135
What is the treatment of warfarin-induced skin necrosis?
Heparin if it occurs Prevent by bridging to coumadin with heparin
136
Name the three elements of Virchow’s triad and what it predicts
Key elements in development of venous thrombosis Stasis, endothelial injury, hypercoaguability
137
What is the key element in development of arterial thrombosis
Endothelial injury
138
What are the three risk factors for DVT?
Stasis, venous injury, and hypercoaguability (Virchow’s triad)
139
What is the treatment for a patient’s first postop DVT?
Warfarin x 1 month
140
What is the treatment for a patient’s second postop DVT?
Warfarin x 1 year
141
What is the treatment for a patient’s third postop DVT?
Warfarin for life
142
What is the treatment for a patient s/p PE
Warfarin for life
143
Name four indications for Greenfield filters
Contraindications to anticoagulation Documented PE while on anticoagulation Free-floating IVC, iliofemoral, or deep femoral DVT Recent pulmonary embolectomy
144
What is the indication for temporary IVCF placement
Patients at high risk for DVT (head injury or prolonged bedrest)
145
What is the treatment for a hemodynamically stable patient with a PE?
Heparin or suction catheter-based intervention
146
What is the role of thrombolytics in pulmonary embolism treatment?
No role, they have not shown improvement in survival
147
When should you go to the OR with a patient with a PE?
If a patient is in shock despite massive inotropes and pressors
148
What is the most common origin of a pulmonary embolism?
Iliofemoral DVT
149
What is the MOA of Amicar (ε-aminocaproic acid)?
Inhibits fibrinolysis by inhibiting plasmin
150
Name three indications for Amicar
DIC; persistent bleeding following cardiopulmonary bypass; thrombolytic overdoses
151
What is the MOA of warfarin?
Prevents vitamin K-dependent decarboxylation of glutamic residues on vitamin K-dependent factors
152
What is the MOA of SCDs (2)?
Improve venous return induce fibrinolysis and release of tPA (tissue plasminogen activator) from endothelium with compression
153
What is the MOA of heparin?
Binds to and activates antithrombin-III to 1000x baseline activity, inactivating factor Xa and thrombin
154
What is the half-life of heparin
60-90 minutes
155
What is the goal PTT for heparin?
60-90seconds
156
How do you reverse heparin and how does it work?
Protamine binds to heparin
157
Which system clears heparin?
Reticuloendothelial system (spleen)
158
Name two adverse effects of long-term heparin use
Osteoporosis; alopecia
159
Which of these are safe/unsafe to use in pregnancy and why: heparin/warfarin?
Heparin does not cross placenta, safe in pregnancy. Warfarin does cross placenta = not safe in pregs
160
What percent of patients get a protamine reaction and how does it present (3 Sx)?
1% of patients, p/w hypotension, bradycardia, decreased heart function
161
What is protamine reaction & what is the MOA of protamine reaction (2)?
Protamine reaction is the IgG/IgE-mediated anaphylactic reaction to administration of protamine that can lead to cardiac collapse. MOA= cross reacts with NPH insulin or previous protamine exposure
162
What is the MOA of LMWH (compared to heparin)
Binds and activates antithrombin III Increases neutralization of just Xa and thrombin (has less of an effect on thrombin compared to heparin but the same effect on Xa)
163
Name two LMWHs
Enoxaparin, fondaparinux
164
Can LMWH be reversed with protamine
nope
165
What is the risk of HIT with LMWH compared to unfractionated heparin?
Lower risk of HIT with LMWH
166
What is the MOA of argatroban? Is it reversible or irreversible?
Reversible direct thrombin inhibitor
167
What is the half-life of argatroban?
50 minutes
168
Where is argatroban metabolized?
In the liver
169
What is the MC indication for argatroban?
In patients with HITT
170
What is the MOA of bivalirudin (angiomax) and is it reversible?
Reversible direct thrombin inhibitor
171
What is the half-life of bivalirudin?
25 minutes
172
Where is bivalirudin metabolized
Proteinase enzymes in plasma / renal
173
What is the most potent direct thrombin inhibitor?
Hirudin (hirulog, from leeches)
174
What is the MOA of hirudin (hirulog) and is it reversible?
Irreversible direct thrombin inhibitor
175
What is the origin and MOA of Ancrod?
Malyan pit viper venom; stimulates tPA release
176
Name three thrombolytics
Streptokinase, urokinase, tPA
177
What is a common problem a/w using streptokinase?
Has high antigenicity
178
What is the MOA of these three thrombolytics? (Streptokinase, urokinase, tPA)
All activate plasminogen
179
How do you monitor anticoagulation with thrombolytics?
Fibrinogen levels
180
What levels of fibrinogen are a/w increased risk of bleeding?
Fibrinogen \<100
181
What is the treatment for thrombolytic overdose?
ε-aminocaproic acid (Amicar)
182
Name five absolute contraindications to thrombolytic use
Active internal bleeding Recent CVA / NSGY (within 3mo) Intracranial pathology Recent GI bleeding
183
Name five major contraindications to thrombolytic use
Recent surgery, organ biopsy, obstetric delivery, or eye surgery (within 10 days) Left heart thrombus Active peptic ulcer Recent major trauma Uncontrolled HTN
184
Name 7 minor contraindications to thrombolytic use
Minor surgery Recent CPR Afib with mitral valve disease Bacterial endocarditis Hemostatic defects (ex: a/w renal or liver disease) Diabetic hemorrhagic retinopathy pregnancy
