Unit 9 - Coagulation Pt 2 Flashcards
1
Q
examples of ADP receptor inhibitors
A
Clopidogrel
Ticlodipine
Prasugrel
Ticagrelor
2
Q
how long should ADP receptor inhibitors be stopped prior to surgery
A
Clopidogrel: 5-7 days
Ticlodipine: 14 days
Prasugrel: 7-10 days
Ticagrelor: 5-7 days
3
Q
how long should GpIIb/IIIa receptor antagonists be stopped before surgery
A
Abciximab: 3 days
Eptifibatide: 1 day
Tirofiban: 1 day
4
Q
how long should non-specific COX inhibitors be stopped before surgery
A
Aspirin: 7 days
NSAIDs: 1-2 days
5
Q
how long should COX2 inhibitors be stopped prior to surgery
A
None
(rofecoxib, celecoxib)
6
Q
when should unfractionated heparin be stopped prior to surgery
A
6 hours
7
Q
when should LMWH be stopped prior to surgery
A
1-2 days
(enoxaparin, daltaparin, tinzaparin)
8
Q
when should thrombin inhibitors be stopped prior to surgery
A
Argatroban: 4-6 hours
Bivalirudin: 2-3 hours
9
Q
when should Fondaparinux be stopped prior to surgery
A
4 days
10
Q
when should warfarin be stopped prior to surgery
A
2-4 days
11
Q
MOA of Fondaparinux
A
factor 10 inhibitor
12
Q
examples of plasminogen activators
A
tPA
streptokinase
13
Q
when to stop tPA before surgery
A
1 hr
14
Q
when to stop streptokinase before surgery
A
3 hrs
15
Q
how do non-specific COX inhibitors prevent platelet aggregation
A
by blocking COX-1
stops conversion of arachidonic acid to prostaglandins and ultimately thromboxane A2
16
Q
MOA of Amicar
A
plasminogen activator inhibitor
17
Q
MOA of aprotinin
A
inhibits plasma, kallikrein, thrombin, and protein C
18
Q
MOA of TXA
A
plasminogen activator inhibitor
19
Q
MOA of DDAVP
A
Stimulates factor 8 and vWF factor release
20
Q
purpose of antifibrinolytics in surgery
A
help preserve integrity of fibrin clot during surgery
21
Q
synthetic derivative of the amino acid lysine
A
TXA
22
Q
MOA of TXA
A
binds to lysine binding site on plasminogen & prevents conversion to plasmin
23
Q
affinity of TXA at modest doses
A
- strong affinity for 5 lysine binding sites on plasminogen
- competitively prevents activation of plasminogen to plasmin
24
Q
affinity of TXA at high doses
A
noncompetitive plasmin inhibitor
25
Most common inherited disorder of platelet function
von willebrand disease
26
plt count in von willebrand disease
normal - it's a **qualitative** plt disorder
27
how is von willebrand factor synthesized
by vascular endothelium & megakaryocytes
28
2 key functions of von willebrand factor
1. Anchors platelet to vessel wall at site of vascular injury (platelet adhesion)
2. Carries inactivated factor 8 in the plasma
29
type 1 von willebrand disease
mild-moderate reduction in amount of vWF produced
30
type 2 von willebrand disease
the vWF that is produced doesn’t work well
31
type 3 von willebrand disease
severe reduction in the amount of vWF produced
32
lab findings with von willebrand disease
* PTT and bleeding time ↑
* No change in PT/INR, plt count, or fibrinogen
33
synthetic analogue of ADH
DDAVP
34
in what type of von willebrand disease can DDAVP be used
type 1, type 2
| Patients with type 3 do not respond because they don’t produce cVW
35
MOA of DDAVP
stimulates endogenous vWF release and increases factor 8 activity
36
dose of DDAVP
0.3 mcg/kg IV
37
how long does a dose of DDAVP improve bleeding time
12-24 hours
38
contents of cryo
factors 8, 13, fibrinogen, and vWF
39
what can be used to treat any type of von willebrand factor disease
cryo
FFP
40
1st line for type 3 vWF disease
purified 8-vWF concentrate
41
treatment of vWF that reduces risk of transfusion-related infection
Purified 8-vWF concentrate:
42
disease of factor 8 deficiency
hemophilia A
43
pt population more likely to be affected by hemophilia A
males
| X-linked
43
pt population more likely to be affected by hemophilia A
males
| X-linked
44
factor 8 activity assoc with spontaneous bleeding
< 1%
(severe disease)
44
factor 8 activity assoc with spontaneous bleeding
< 1%
(severe disease)
45
factor 8 activity assoc with increased surgical bleeding
activity 6-30% of normal
46
lab values in hemophilia A
* PTT ↑
* No change in PT/INR, Plt count, bleeding time, or fibrinogen
47
SE of giving DDAVP rapidly
hypotension
| r/t vasodilation
48
disease of factor 9 deficiency
hemophilia B
49
severe vs mild hemophilia B disease
* Severe disease (factor 8 activity < 1%) assoc. with spontaneous bleeding
* Mild disease (factor 8 activity 6-30% normal) doesn’t cause spontaneous bleeding but is assoc with increased surgical bleeding
50
half life of factor 8 concentrate
8-12 hours
51
half life of factor 9 concentrate
18-24 hours
52
risk of giving factor 9 concentrate
thromboembolic complications
53
when might recombinant factor 7 be needed in a hemophilia patient
when they develop inhibitors that prevent exogenous factors from achieving therapeutic goals
54
MOA of recombinant factor 7
Exact MOA unclear
both classic and contemporary cell-based theories of coagulation suggest that factor 7 contributes to **thrombin generation** by facilitating tissue factor at the site of vascular injury and on the surface of the platelet
55
risks of recombinant factor 7
arterial & venous thrombosis
| MI, embolic stroke, DVT, PE
56
3 Conditions Assoc. with High Risk DIC
1. Sepsis (highest risk = gram negative bacilli)
2. OB complications (highest risk = preeclampsia, placental abruption, and AFE)
3. Malignancy (highest risk = adenocarcinoma, leukemia, lymphoma)
57
dose of recombinant factor 7 for hemophilia pts
90-120 mcg/kg
58
MOA of recombinant factor 7
exact MOA unclear
classic and contemporary cell-based theories of coagulation suggest that factor 7 contributes to thrombin generation by **facilitating tissue factor** at the site of vascular injury and on the surface of the platelet
59
adverse effects assoc with recombinant factor 7
Can increase the risk of arterial thrombosis (Ml and embolic stroke) as well as venous thrombosis (DVT or pulmonary embolism)
60
what is DIC
disordered clotting & fibrinolysis that leads to simultaneous occurrence of hemorrhage and systemic thrombosis
61
lab values assoc with DIC
↑ PT/PTT, D-dimer
↓ platelets, fibrinogen
62
how are procoagulants kept at bay in normal physiology
antithrombin and tissue factor pathway inhibitor (TFPI)
63
how does DIC lead to organ failure
systemic activation of coagulation = increased fibrin formation = microvascular thrombosis = organ failure
64
what leads to hemorrhage in DIC
Widespread **fibrin** deposition consumes the body's supply of fibrinogen, coagulation factors, and platelets = hemorrhage
65
s/s DIC
* ecchymosis
* petechiae
* mucosal bleeding
* bleeding at IV puncture sites
* prolonged PT and PTT
* increased D-dimer and fibrin split products
* decreased fibrinogen and antithrombin
66
3 conditions assoc with high risk for DIC
1. Sepsis
2. OB complications
3. Malignancy
67
infections at highest risk for DIC
gram negative bacilli
68
OB complications at highest risk for DIC
preeclampsia
placental abruption
AFE
69
malignancies at highest risk for DIC
adenocarcinoma
leukemia
lymphoma
70
treating DIC
* Definitive treatment: reverse cause
* Treat hypovolemia with IV fluids
* Replace consumed blood components with FFP, platelets, and cryo
* IV heparin or LMWH for severe microvascualr thrombosis
71
factors inactivated by antithrombin
factors 9, 10, 11, & 12
| ultimately leads to thrombin (factor 2a) inhibition
72
factors inactivated by antithrombin
factors 9, 10, 11, & 12
| ultimately leads to thrombin (factor 2a) inhibition
73
causes of antithrombin deficiency
* congenital
* acquired from repeated heparin admin (consumes body's supply of AT)
74
treatment for antithrombin deficiency
* AT concentrate
* FFP
## Footnote
Patients with antithrombin deficiency are unresponsive to heparin
74
treatment for antithrombin deficiency
* AT concentrate
* FFP
## Footnote
Patients with antithrombin deficiency are unresponsive to heparin
75
treatment for antithrombin deficiency
* AT concentrate
* FFP
## Footnote
Patients with antithrombin deficiency are unresponsive to heparin
76
what causes Heparin-Induced Thrombocytopenia
* Occurs when the body mounts an immune response against heparin after it binds to PF4
* IgG antibodies activate platelets
* results in uncontrolled clot formation
77
patho of HIT type 1
* Heparin-induced platelet aggregation
* Occurs after large heparin dose
78
onset of HIT type 1
1-4 days after heparin admin
79
plt count in HIT type 1 vs type 2
type 1 = < 100,000
type 2 = < 50,000
80
treatment of HIT type 1
resolves spontaneously even if heparin is continued
81
patho of HIT type 2
* antiplatelet IgG antibodies attack factor 4 immune complex = plt aggregation
* occurs after **any** heparin dose
82
onset of HIT type 2
5-14 days after heparin admin
83
morbidity of HIT type 1 vs type 2
type 1 = minimal morbidity
type 2 = high risk of amputation and death
84
treatment of HIT type 2
* d/c heparin
* anticoagulate with direct thrombin inhibitor (Bivalirudin, Hirudin, Argatroban)
85
risks of protein C or S deficiency
can produce hypercoagulable state and ↑ risk thrombus
| Creates a feedback mechanism that prevents unnecessary clot formation
85
risks of protein C or S deficiency
can produce hypercoagulable state and ↑ risk thrombus
| Creates a feedback mechanism that prevents unnecessary clot formation
86
treatment of protein C and S deficiency
* Start thromboembolism treatment with heparin - pt will switch to Warfarin
* May require life-long anticoagulation with warfarin
87
factor 5 leiden mutation
Causes resistance to anticoagulant effect of protein C
88
treatment of Factor 5 Leiden Mutation
* anticoagulation only for pts with thromboembolism
* Lifelong anticoagulation is unwarranted unless pt has recurrent thrombotic events
89
Patho of sickle cell anemia
* Inherited disorder that affects erythrocytes
* Amino acid substitution (valine is substituted for glutamic acid) on the beta globulin chain alters BC geometry
* alters RBC function
90
how does sickle cell anemia alter RBC function
* deoxygenation of HgbS leads to sickling
* if severe, sickling causes RBCs to clump together and cause mechanical obstruction
* sickled cells more prone to hemolysis and removal by spleen
91
lifespan of sickled cells vs normal blood cells
sickled = 12-17 days
normal = 120 days
92
anesthetic management of sickle cell anemia
focuses on avoiding triggers that promote sickling
avoid: pain, hypothermia, hypoxemia, acidosis, dehydration
93
most common manifestation of sickle cell disease
Vaso-Occlusive Crisis
94
med that reduces incidence and severity of sickle cell crisis
hydroxyurea
95
causes of acute chest syndrome
thrombosis
embolism
infection
96
diagnosis of acute chest syndrome
requires new lung infiltrates on CXR and at least one: chest pain, cough, dyspnea, wheezing
97
potential causes of acute chest syndrome
hypoventilation, narcotics, splinting, pain
98
what causes sequestration crisis in sickle cell
Occurs when spleen removes RBCs from circulation at a faster rate than the bone marrow produces them
99
consequences of sequestration crisis in sickle cell
anemia
hemodynamic instability
100
why are pts with sickle cell at risk for aplastic crisis
RBCs with HgbS have a short half life
even a small amount of bone marrow suppression can cause anemia
101
common cause of aplastic crisis in sickle cell pts
parvovirus B19
102
sickle cell patients at highest risk for pneumococcal disease
children
103
pneumococcal disease prophylaxis in sickle cell pts
pneumococcal vaccination and daily penicillin up to 5 yrs of age
104
diagnosis seen in 50% of sickle cell patients
asthma
105
complication in 10% of sickle cell patients
pulmonary HTN
