Hemostatsis Flashcards
1
Q
Normal Hemostasis occurs in 3 steps
A
- Vasoconstriction
- Platelet aggregation (1st)
- Fibrin formation (2nd)
2
Q
Primary Hemostasis
A
Platelet plug
3
Q
Secondary Hemostasis
A
make platelet plug strong with fibrin
4
Q
Molecules that turn fibrinogen into fibrin
A
coagulation factors
5
Q
what is the point of the coagulation cascade?
A
to create fibrin to strengthen platelet plug
6
Q
Primary and Secondary hemostasis forms what?
A
Clot
7
Q
What triggers primary hemostasis events?
A
Damage of the vascular wall exposes blood to
subendothelial tissue
8
Q
What doe s endothelin do?
A
vasoconstrictor
9
Q
What does nitric oxide and prostacyclin do?
A
vasodilator
10
Q
The platelet plug formation is the result of a series of reactions (4)
A
adhesion
aggregation
release of granule content
morphological changes
11
Q
What is adhesion dependent on interaction between:
A
platelets
the von Willebrand factor (VWF)
12
Q
2 main glycoproteins on platelet
A
GP1b-V-IX
Integrin α2β1
13
Q
where does VWF come from?
A
free floating
secreted by endothelial cells
14
Q
VWF serves as a bridge between
A
collagen in the subendothelium
and
platelet membrane glycoprotein
Ib-V-IX (GP1b-V-IX)
15
Q
Does adhesion occur better in large or small arterioles?
A
small
16
Q
The adhesion process functions better under high
shear stress because
A
high shear unfolds the VWF
thus exposing the binding sites for GPIb-V-IX
17
Q
Where does adhesion occur best?
large vein
small vein
large artery
small arteriole
A
small arteriole
18
Q
What are the platelet receptors for collagen?
A
Integrin α2β1
GPVI
GPV
19
Q
Aggregation is a conformational change of the platelet Integrin α2β1 to expose binding sites for? - 4
A
adhesive proteins:
fibrinogen
VWF
fibronectin
thrombospondin
20
Q
What are the adhesive proteins of aggregation?
A
fibrinogen
VWF
fibronectin
thrombospondin
21
Q
two most common
forms of severe inherited bleeding disease
A
Hemophilia A
Hemophilia B
22
Q
Transmission of Hemophilia A and B
A
X-linked recessive traits
23
Q
female carriers of hemophilia can also express a mild bleeding tendency, often manifest as
A
menorrhagia
heavy menstrual bleeding
24
Q
Diagnosis of hemophilia (3)
A
1) combination of clinical and laboratory features.
2) (+) Family Hx in approximately 60% of cases
2) The clinical manifestations of hemophilia
25
Clinical features of severe hemophilia
episodes of spontaneous musculoskeletal bleeding
(~20-30/yr) with clinical events starting around 1-2
years of age
26
Clinical features of moderately severe hemophilia
usually do not manifest spontaneous bleeding
27
Clinical features of mild hemophilia
only bleed on provocation and can sometimes present late in adult life at the time of a surgical or dental intervention
28
Severe hemophilia factor level
<1%
29
Moderately severe hemophilia factor level
1-5%
30
Mild hemophilia factor level
5-40%
31
Laboratory diagnosis of hemophilia (2)
1) requires an accurate assessment of FVIII or FIX
levels with one-stage clotting assays
2) the initial phenotypic diagnosis of hemophilia is
complemented with molecular genetic testing to identify the causative FVIII or FIX mutation.
32
Current treatment of hemophilia - 3
1) involves various forms of protein replacement
therapy.
2) utilization of recombinant clotting factor
concentrates with prolonged circulating half-lives
3) gene therapy is now evident, that AAV-mediated
gene transfer is feasible and results in long-term
expression of therapeutic FIX levels in hemophilia B
33
most common inherited bleeding disorder in
| humans
vWD
| von Willebrand Disease
34
vWD
von Willebrand Disease
35
Who is more affected by vWD? males or females
females outnumber males by 2:1
36
How many subtypes of vWD?
3: type 1, type 2, and type 3
37
type 1 vWD
quantitative deficiency of
functionally normal VWF. In most populations this
accounts for ~65% of VWD cases
38
most common type of vWD
type 1 vWD
39
Type 2 vWD
represents a group of qualitative VWF variants (types 2A, 2B, 2M and 2N)
comprising approximately 30% of VWD
40
type 3 vWD
virtual absence of VWF (with
accompanying very low levels of FVIII) occurring in
approximately 1 in 1 million of the population
41
most rare type of vWD
type 3 vWD
42
consideration of diagnosis of vWD (non lab) - 3
1. a personal history of excessive mucocutaneous bleeding
2. laboratory test results consistent with VWD
3. family history of the condition.
43
lab tests for diagnosis vWD
1. the VWF:Ag
| 2. VWF activity assay (prior VWF:RCo test)
44
Clinical condition with bleeding AND thrombosis
liver cirrhosis
45
mucocutaneous bleeding suggests disorders of
platelets
von Willebrand factor (vWF)
vascular bleeding disorder
46
examples of mucocutaneous bleeding
petechiae, bruising, epistaxis, gastrointestinal bleeding and/or menorrhagia
47
Bleeding into muscles and joints, soft tissues and
| delayed surgical bleeding suggests disorders of
coagulation factors
48
Initial tests to screen for bleeding disorders should
| include:
- a complete blood count (CBC)
- blood film
- whole blood platelet function testing
- prothrombin time (PT)
- activated partial thromboplastin time (APTT)
- Factor XIII testing
49
The main platelet functions required to maintain
| vascular integrity and to ensure primary hemostasis are - 5
1. adhesion
2. activation
3. secretion of various alpha and dense granule
4. Aggregation
5. procoagulant activity
50
DIC - abbreviation
Disseminated Intravascular Coagulation
51
Disseminated Intravascular Coagulation
pathological process characterized by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body
aka
systemic activation of hemostasis leads to
widespread intravascular fibrin deposition with
associated depletion of prohemostatic and
anticoagulant factors W/ secondary fibrinolysis
52
What are the regulatory mechanisms that control the
extent of fibrin formation after coagulation is
triggered?
antithrombin mechanism,
the protein C–protein S system, the fibrinolytic
system, and the tissue factor pathway inhibitor
mechanism.
53
main regulatory proteins of fibrin formation
antithrombin, protein C, and protein S
54
What is Antiphospholipid syndrome?
autoimmune
disorder that increases the risk of venous and arterial
thrombosis as well as pregnancy complications
attributable to a reduction in placental perfusion
55
Natural inhibitors of coagulation - 3
1. Antithrombin (AT);
2. Components of the protein C pathway (thrombomodulin,
protein C, protein S)
3. Tissue factor pathway inhibitor (TFPI)
56
AT - abv
Antithrombin
57
Components of the protein C
| pathway - 3
thrombomodulin,
| protein C, protein S
58
TFPI - abv
Tissue factor pathway inhibitor
59
Exclusionary test for low clinical probability for DVT
(-) D-dimer test
60
Pretest Probability is defined as the probability of a patient having the target disorder before a diagnostic test result is known.
the probability of a patient having the target disorder before a diagnostic test result is known.
61
Confirmatory test for high clinical probability for DVT
imaging diagnostic
techniques are required, typically compression
ultrasound for suspected DVT and computed
tomography of pulmonary arteries for suspected PE
62
standard initial treatment for DVT
subcutaneous
| low-molecular-weight heparin (LMWH) without monitoring.
63
The antiphospholipid syndrome is
auto-immune disease characterized by thrombotic complications in both arteries and veins as well as fetal losses in combination with the presence of so-called
antiphospholipid antibodies in plasma of these patients
a disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss
64
Warfarin is used for
oral anticoagulant
65
Warfarin MOA
vitamin K antagonist and blocks γ- carboxylation of a series of glutamic acid residues
during the synthesis of factors II, VII, IX, and X, and proteins C and S
66
Which tests are used to monitor Warfarin?
```
international normalized ratio (INR), and the partial
thromboplastin time (PTT)
```
67
Heparin inhibits what?
thrombin - indirectly
68
Heparin binds to...
antithrombin and increases its
ability to inhibit thrombin, factor Xa, and, to a lesser
extent, other serine protease coagulation factors.
69
What is Heparin-induced thrombocytopenia (HIT)?
a complication of heparin therapy in which antibodies develop against complexes of heparin and
platelet factor 4 (PF4).
70
What do target-specific oral anticoagulants do?
directly inhibit
| either thrombin or factor Xa
71
Antiplatelet therapy is used for
the prevention of recurrent stroke or myocardial infarction
72
Coagulation Factor Name, Source, and Pathway
Factor I
Name: Fibrinogen
Source: Liver
Pathway: Common
73
Coagulation Factor Name, Source, and Pathway
Factor II
Name: Prothrombin
Source: Liver
Pathway: Common
74
Coagulation Factor Name, Source, and Pathway
Factor III
Name: Tissue Factor / thromboplastin
Source: Damaged tissues and activated platelets
Pathway: Extrinsic
75
Coagulation Factor Name, Source, and Pathway
Factor IV
Name: Calcium Ions
Source: Diet, bones, platelets
Pathway: All
76
Coagulation Factor Name, Source, and Pathway
Factor V
Name: Labile factor
Source: Liver and platelets
Pathway: Extrinsic and intrinsic
77
Coagulation Factor Name, Source, and Pathway
Factor VII
Name: Proconvertin
Source: Liver
Pathway: Extrinsic
78
Coagulation Factor Name, Source, and Pathway
Factor VIII
Name: Antihemophilic factor / Antihemophilic factor A
Source: Liver
Pathway: Intrinsic
79
Coagulation Factor Name, Source, and Pathway
Factor IX
Name: Christmas factor / antihemophilic factor B
Source: Liver
Pathway: Intrinsic
80
Coagulation Factor Name, Source, and Pathway
Factor X
Name: Stuart-Power factor / thrombokinase
Source: Liver
Pathway: Extrinsic and Intrinsic
81
Coagulation Factor Name, Source, and Pathway
Factor XI
Name: Plasma thromboplastin antecedent / anthihemophilic factor C
Source: Liver
Pathway: Intrinsic
82
Coagulation Factor Name, Source, and Pathway
Factor XII
Name: Hageman factor / contact factor / antihemophilic factor D
Source: Liver
Pathway: Intrinsic
83
Coagulation Factor Name, Source, and Pathway
Factor XIII
Name: Fibrin-stabilizing factor
Source: Liver and platelets
Pathway: Common
84
Vitamin K dependent factors
Factors: 2,7,9,10
II
VII
IX
X
Protein C
85
Thrombin interacts with these factos
Factors: 1, 5, 8
I
V
VIII
86
Abnormalities and common causes indicated by prolonged
Thrombin Time (TT)
Abnormality: Fibrinogen or inhibition of thrombin by heparin
Cause:
DIC
Heparin Therapy
87
Abnormalities and common causes indicated by prolonged
Prothrombin Time (PT)
Abnormality: Deficiency in on or more of Factors: VII, X, V, II, I (fibrinogen)
Cause:
liver disease
warfarin therapy
DIC
88
Abnormalities and common causes indicated by prolonged
Activated partial thromplastin time (APTT)
Abnormality: Deficiency in one of more of factors: XII, XI, IX, VIII, X, V, II, fibrinogen
Cause:
Hemophilia
Christmas Disease
89
Abnormalities and common causes indicated by prolonged
Fibrinogen quantitation
Abnormality: Fibronogen deficiency
Cause:
DIC
Liver disease
90
Disorders of Primary Hemostasis
- bleeding due to vessel wall abnormalities
- bleeding due to reduced platelet number
- bleeding due to decreased platelet function
91
Thrombocytopenia
abnormally low level of platelets
92
Test Findings For
DIC
Platelet: Decrease
APTT: Increase
PT: Increase
TT: Increase
93
Test Findings For
Thrombocytopenia
Platelet: Decrease
APTT: Normal
PT: Normal
TT: Normal
94
Test Findings For
vWD
Platelet: Normal
APTT: Normal
PT: Normal
TT: Normal
95
Test Findings For
Vitamin K deficiency
Platelet: Normal
APTT: Increase
PT: Incrase
TT: Normal
96
Which factor does the liver NOT produce?
Factor VIII
97
DIC scores
if ≥ 5, compatible with over DIC: repeat daily
if
98
Deficiency in which proteins incrase risk for venous thrombosis
Antithrombin
Protein C
Protein S
99
Antithrombotic Therapies - 4
- VITAMIN K ANTAGONISTS
- ANTITHROMBIN-DEPENDENT PARENTERAL ANTICOAGULANTS
- TARGET-SPECIFIC ANTICOAGULANTS
- ANTIPLATELET THERAPY
100
Drugs that increase clearance of warfarin (decreased INR)
Barbituates
Rifampin
Hyperforin
101
Drugs that decrease clearance of warfarin (increased INR)
Amiodarone
Fluconazole
Miconazole
Phenylbutazone
Sulfamethoxazole
102
Adhesion mediated by
GPIb (receptor for vWF)
GPIa-IIa (receptor for collagen).
103
Degranulation (release reaction) includes the release of
α and dense granules and the synthesis/release of thromboxane A2(TXA2)
104
Platelet α granules contains large molecules - 5
fibrinogen
platelet derived growth factor (PDGF)
von Willebrand factor (vWF),
P-selectin,
platelet factor 4(PF4)
105
Platelet dense granules contain small molecules - 4
adenosine diphosphate (ADP),
adenosine triphosphate (ATP),
serotonin (5-HT),
calcium
106
Degranulation is stimulated by platelet agonists including: 6
epinephrine
ADP
thrombin
platelet activating factor (PAF)
collagen
TXA2
107
Aggregation (attachment to other platelets) is mediated by
GPIIb/IIIa
108
Intrinsic Pathway Factors
Factors include
```
XII
XI
IX
VIII
prekallikrein / high molecular weight kininogen (HMWK)
```
109
Tenase complex on intrinsic pathway
Calcium
VIIIa
IXa
110
Extrinsic Pathway Factor
VII
111
Common Pathway Factors
X
II (prothrombin)
Fibrinogen (I)
112
Common name of Factor Ia
fibrin
113
Fibrinogen is a hexamer composed of pairs of... 3
Polypeptides:
| α,β, and η
114
Polymerized fibrin molecules are called
Protofibrils
115
what protein binds platelet to platelet?
GP2b-3a complex
116
what protein binds platelet to vWF?
GP1b
117
which of the following will cause bleeding secondary to adhesion?
a. decrease vwf
b. decrease or absent GPIb
c. decrease or absent GPIIb-IIIa complex
a. decrease vWF
| b. decrease or absent GPIb
118
what is the protein responsible for aggregation?
GPIIb-IIIa complex
119
Deficiency in GPIIb-IIIa complex is called?
Glanzmann's thrombasthenia
120
what step in the coagulation pathway is being affected by the Glanzmann's thrombasthenia?
platelet aggregation
121
What is von Willebrand disease
deficiency or defect in plasma von Willebrand factor
122
What is Bernard-Soulier syndrome
deficiency or defect in glycoprotein [GP]Ib/IX
123
What are disorders of adhesion?
von Willebrand disease
Bernard-Soulier syndrome
124
What is Congenital afibrinogenemia?
deficiency of plasma fibrinogen
125
What is Glanzmann thrombasthenia?
deficiency or defect in GPIIb/IIIa
126
What are disorders of aggregation?
Congenital afibrinogenemia
Glanzmann thrombasthenia
127
Which of the follow is/are disorders of adhesion?
Bernard-Soulier syndrome
Congenital afibrinogenemia
Glanzmann thrombasthenia
von Willebrand disease
von Willebrand disease
Bernard-Soulier syndrome
128
Likely factors involved with:
PT: ⬆︎
aPTT: ↔︎
Factor VII
129
Likely factors involved with:
PT: ↔︎
aPTT: ⬆︎
Factor VIII
130
Likely factors involved with:
PT: ⬆︎
aPTT: ⬆︎
Factor V
Factor X
Fibrinogen
LAC
131
Likely factors involved with:
PT: ↔︎
aPTT: ↔︎
XIII
| LAC
132
What are disorders of release reaction?
Plateler release defect
Storage pool disease
133
(Platelet Storage Pool Disorders)
Dense granules disorders
Hermansky-Pudlak
Chediak-Higashi
Wiskott-Aldrich syndrome
134
(Platelet Storage Pool Disorders)
Platelet α granule disorders
Gray platelet syndrome
135
Which of the following is/are dense granules disorders?
a. Chediak-Higashi
b. Gray platelet syndrome
c. Hermansky-Pudlak
d. Wiskott-Aldrich syndrome
a, c, d
136
antithrombic events:
| release of 2
t-PA (fibrinolysis)
thrombomodulin (blocks coagulation cascade)
137
Thrombin Time (TT) screens for: - 2
DIC
| Heparin Therapy
138
Prothrombin Time (PT) screens for: - 3
Liver Disease
Warfarin Therapy
DIC
139
Activated Partial Thromboplastin Time (aPTT) screens for - 2
Hemophilia
| Christmas Disease
140
Fibrinogen Quantitation screens for - 2
DIC
| Liver Disease
141
Which test/s would you request for DIC?
TT
PT
Fibrinogen Quant
142
Which test/s would you request for liver disease?
PT
| Fibrinogen Quant
143
Which test/s would you request for Heparin monitoring?
TT
144
Which test/s would you request for Warfarin monitoring?
PT
145
Steps of Extrinsic Pathway of clotting
1. Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor (TF) forming an activated complex (TF-Factor VIIa)
2. TF-Factor VIIa activates FX
3. Factor Xa and co-factor Factor Va form the prothrombinase complex, which activates prothrombin to thrombin
146
Steps of Intrinsic Pathway of clotting
1. Blood trauma or contact with collagen activates FXII
2. (Factor XIIa + HMW kininogen + prekallikrein) complex activates Factor XI
3. (Factor XIa + Ca) activates Factor IX
4. (Factor IXa, Factor VIII + platelet phospholipids + Factor III/Tissue Factor) activates Factor X.
5. Factor Xa and co-factor Factor Va form the prothrombinase complex, which activates prothrombin to thrombin
