Coagulation-Fung Flashcards
(196 cards)
1
Q
What are the three steps of normal hemostasis?
A
Vasoconstriction
platelet aggregation
fibrin formation
2
Q
What are the three steps of primary hemostasis?
A
- adhesion
- degranulation
- aggregation
3
Q
What is this:
with injury Von Willbrand Factor and collagen are exposed on the subendothelial basement membrane
Platelet receptor GPIb binds to Von willebrand factor
A
Adhesion
4
Q
What is this:
- platelets release their alpha and dense granules
- synthesize and release TXA2
A
Degranulation
5
Q
What is this:
-Platelet receptor GPIIB/IIIa and fibrinogen allows platelets to aggregate to one another
A
aggregation
6
Q
Where are almost all factors except for Von willbrand factor produced?
A
liver
7
Q
Where is von willebrand factor produced?
A
endothelial cells
megakaryocytes
8
Q
What is another name for factor I?
A
fibrinogen
9
Q
What is another name for factor II?
A
Prothrombin
10
Q
What is another name for factor VIII?
A
antihemophilic factor
11
Q
What is another name for factor IX?
A
christmas factor
12
Q
What is another name for factor XII?
A
Hagemann factor
13
Q
What is another for factor XIII?
A
Fibrin stabilizing factor
14
Q
What is the common pathway for the intrinsic and extrinsic pathways of coagulation?
A
factor X-> Xa
15
Q
When wil the intrinsic coag cascade happen?
A
with contact phase
16
Q
When will the extrinisc coag cascade happen?
A
tissue injury and tissue factor
17
Q
What is the intrinisc pathway?
A
XII->XIIa-> which converts IX to IXa and VIII is converted to VIIIa by IIa. VIIIa and IXa will make X which will go to Xa which will convert prothrombin (II) to thrombin (IIa) which will convert fibrinogen to fibrin. Factor XIII will then turn into factor XIIIa which wil convert fibrin into cross linked fibrin
18
Q
What is the extrinsic pathway?
A
VII is converted to VIIa which converts X to Xa* which will combine with Va* (made from IIa converting V to Va)
Va and Xa* convert prothrombin (ii) into thrombing (iia) which converts fibrinogen to fibrin which when combined with XIIIa will create cross linked fibrin
19
Q
What makes up the prothrombinase complex?
A
Va and Xa
20
Q
What makes up the tenase complex?
A
VIIIa, Xa, Ca
21
Q
What is this:
the balance between clotting and thrombosis
A
hemostasis
22
Q
Hemostasis is a precisely orchestrate process involving (blank), (blank), and (Blank)
A
pateletes
clotting factors
endothelium
23
Q
Where does hemostasisi occur?
A
at site of vascular injury and culminates in the formation of a blood clot
24
Q
What are 2 disorders of hemostasis?
A
hemorrhagic disorders
thrombotic disorders
25
What is this:
| characterized by excessive bleeding
Hemorrhagic disorders
26
What is this:
| Characterized by clot formation
thrombotic disordes
27
Why do we get vasoconstriction in hemostasis and how?
-reduces blood flow to area, -mediated by reflex neurogenic mechanisms and augmented by local secretion of endothelin
(transient effect)
28
What is primary hemostasis?
- platelets adhere to endothelium and are activated
| - this process leads to agregation and the beginning of a clot
29
What is secondary hemostasis?
- tissue factor is exposed at the site of vascular injury
| - sets in motion a cascade of reactions that leads to thrombin fomration
30
(blank) release causes vasoconstriction
endothelin
31
At the site of injury you will get reflex (Blank)
vasoconstriction
32
THe blood vessel consists of three layers what are they?
Intima – contains endothelium
Media – layer of smooth muscle
Adventitia – rich in connective tissue
33
Vascular endothelium is a dynamic organ that actively regulates hemostasis by ....?
- inhibiting platelets
- suppressing coag
- promoting fibrinolysis
- mod vascular tone and permeability
34
What are the anti-thrombotics for blood vesses?
```
heparin
protein C and protein S
tissue plasminogen activator
prostacyclin
nitric oxide
thrombomodulin
protein C receptor
Tissue factor pathway inhibitor (TFPI)
```
35
What are the prothrombics for blood vessels?
```
Factor V
tissue factor
plasminogen activator inhibitor-1 (PAI-1)
thromboxane
platelet activating factor
vWF
```
36
Upon vascular injury, what happens?
- tissue factor is released
- extracellular matrix (collagen) is exposed
- media and adventitia mediate vasoconstriction
37
Blood vessel exposure to (blank) and (blank) sets the stage for platelets adherence and activation
collagen and vWF
38
Give me the 5 steps of primary hemostasis?
1) platelet adhesion
2) shape change
3) granule release (ADP, TXA2)
4) recruitment
5) aggregation (hemostatic plug)
39
(blank) are derived from megakaryocyte maturation
platelets
40
What is this:
| anucleate structure consisting of a cytoskeleton and cytoplasmic granules
Platelets
41
What are the components of the cytoplasm?
```
GP Ib/V/IX
GP IIb/IIIa
GP Ic/IIa
CD62P (p selectin)
Thrombin receptor
ADP receptor
GP Ia/IIa
Red cell antigens
Class I MHC antigen
```
42
What does G Ib/V/IX bind?
vWF
43
What does GP IIb/IIIa bind?
fibrinogen
44
What does GP Ic/IIa bind?
fibrinonectin
45
What does CD62p (p selectin) bind?
adhesion molecule
46
What does the thrombin receptor bind?
initiates platelet activation when bound by thrombin
47
What does the ADP receptor bind?
initiates platelet activation when bound by ADP
48
What does GP Ia/IIa bind?
binds collagen
49
What do red cell antigens bind?
ABO, P, I, i, le (no Rh)
50
What does Class I mHC antigen bind?
HLA-A, HLA-B, HLA-C
51
What are the alpha granules of platelets (about 75-80 per cell)?
```
vWF
Fibrinogen
Factor V
VEGF, EGF, PDGF
angiostatin, thrombospondin, endostatin
PF-4, IL-8, CCL-5
```
52
What are the dense granules of platelets (less than 12 per cell)?
ATP
ADP
Calcium
Serotonin
53
Platelets adhere to the exposed (blank) and (blank) at the site of injury.
collagen
| vWF
54
Platelet adhesion is mediated by platelet (blank) binding to vWF
GP Ib/V/IX
55
Platelet activation leads to...?
shape change
release of alpha and dense granules (ADP)
initiation of thromboane A2 pathway
GP IIb/IIIa to change to its active form
56
What are the four steps to secondary hemostasis?
1) tissue factor
2) phospholipid expression
3) thrombin activation
4) fibrin polymerization
57
Okay so say you have a tissue injury and you have collagne and VWF exposed, then what?
Gp1a and GP1b binds and then the platelet releases ADP, TXA2, 5-HT which stimulates the platelet to become activated and degranulate
58
What does antithrombin regulate?
```
Thrombin
FIXa
FXa
FXIa
FXIIa
```
59
What does activated protein C (APC) regulate?
FVa
| FVIIIa
60
What is the tissue factor pathways inhibitor/extrinisc pathway inhibitor?
tissue factor-FVIIa-FXa
61
What does plasmin do?
degrades fibrin (PA converts plasminogen to plasmin)
62
Evalutation of hemostasis can be divided into what 2 categories?
platelets
| coagulation
63
What are the studies you can do on platelets to evaluate hemostasis?
- platelet cout
- bleeding time
- platelet aggregometry (function test)
- platelet flow cytometry
64
What are the studies you can don on coagulation to evaluate hemostasis?
aPTT
PT
Thrombin Time
others
65
What is bleeding time used for?
used to screen qualitative platelet disorders or von willebrand disease
(dont used in patient w/out a hitory of excessive bleeding0
66
Is bleeding time a useful test to assess risk of bleeding during surgery?
no
67
What is the normal range of bleeding time?
1.5-9.5 minutes
68
Where will you see prolongations in bleeding time?
- von willebrand disease
- inherited platelet disorders
- uremia
- aspirin ingestion
- low platelet counts (<100,000)
69
What is platelet aggregometry?
in vitro evaluation of platelet aggregation
70
Where do you perform platelet aggregometry?
performed on platelet-rich plasma that is exposed to various agonists such as ADP, epinephrine, arachidonate, collagen, ristocetin
71
What is platelet flow cytometry used for?
- to diagnose deficiencies of platelet surface glycoproteins
| - disorders of platelet activation
72
How does platelet flow cytometry work?
detects cell surface proteins w/ fluorescently labeled antibodies
73
What how do you determine platelet count and what is normal?
w/ an automated counter
| Referance range: 140-400 X 10^9 cells/mL
74
What is prothrobin time (PT) used for?
used to evaluate the extrinsic and common pathways
75
How does prothrombin time test work?
tissue factor and thromboplastin added to plasma w/ excess calcium and the time to clot is measured
76
What is the reference range of prothrombin time?
11-13.5 seconds
77
What can cause prolongation of coagulation?
```
deficiencies and inhibitors of:
Factor VII
Factor X
Factor V
Factor II
Fibrinogen
```
78
What do you use to monitor warfarin (coumadin) therapy?
prothrombin time
79
What is the INR (international normalized ratio) for?
used to reduce interlab variation that results from differing thromboplastin sensitivities to coumadin
80
What is used as a valid standardizing calculation in coumandized patients with PT in the low range
INR (international normalized ratio)
81
What is activatd partial thromboplastin time (aPTT)?
used to evaluate intrinsic and common pathways
82
How does the activated partial thromboplastin time test work?
Phosopholipid is added to plasma with excess calcium and the time to clot is measured.
83
What is the reference range for activatd partial thromboplastin time (aPTT)?
27-35 seconds
84
Why would you have prolongation in activated partial thromboplastin time (aPTT)?
```
Deficiencies and inhitors of :
Factor XII
Factor IX
Factor X
Factor II
Factor XI
Factor VIII
Factor V
Fibrinogen
```
85
What is activated partial thromboplastin time (aPTT) used to monitor?
heparin, hirudi, or argatroban therapy
86
What is thrombin time (TT) used for?
to test for the presence of functional fibrinogen
87
How do you do the thrombin time (TT) test?
thrombin is added to patient's plasma and the time to clot is measured
88
What is the reference range of thrombin time (TT)?
15-19 seconds
89
What is prolongation in thrombin time (TT) caused by?
heparin, hirudin, argatroban and dysfibrinogenemia
90
What are mixing studies for?
Used to deterine cause of prolonged clotting times (PT, PTT,TT) AND
to screen for the presence of inhibitors
91
What is the process behind mixing studies?
- exclude the presence of heparain through heparin neutralization
- mix patient's plasma w/ normal test plasma, incubate and repeat test
92
If you do a mix study and there is at least 50% activity (correction of value) then what does this mean?
coagulation prolongation is due to a factor deficiency
93
If you do a mix study and there is less than 50% activity (correction of value), prolongation is due to presence of a (blank)
inhibitor
94
What does the presence of D-dimers show us?
formd by plasmin mediated degredation of fibrin, presence indicates that fibrin has been formed and degraded (clotting)
95
What is the von Willebrand factor assay (ristocetin cofactor assay)?
Version of platelet aggregation where patient plasma is added to formalin-fixed normal platelet in the presence of ristocetin. Normal patients will have platelet agglutination but vWF deficient patients will have decreased agglutination
96
What is the Anti-Xa assay for?
used to monitor either unfractionated or low molecular weight heparin
97
What are factor assays for?
| When do yo do it?
to assess individual factor activity
| Done after an intial mixing study shows a factor deficiency!!
98
```
What are these:
Factor VIII inhibitor assay
Fibrinogen activity
Protein C activity
Protein S activity
```
Other assays
99
Clinically most bleeding disorders present as either (blank) or (blank) bleeding
platelet-type bleeding
| coagulation-type bleeding
100
If you see petechia what type of bleeding disorder should you be thinking of?
Platelet-type bleeding disorder
101
If you see hemarthroses, what type of bleeding disorder should you be thinking of?
coagulation-type bleeding disorder
102
If you see deep hematomas, what type of bleeding disorder should you be thinking?
coagulation-type bleeding disorder
103
If you see delayed bleeding, what type of bleeding disorder should you be thinking?
coagulation-type bleeding disorder
104
If you see mucosal bleeding what type of bleeding disorder should you be thinking?
platelet-type bleeding disorder
105
If you have a female with a bleeding disorder what should you be thinking?
platelet-type bleeding disorder
106
If you have a male with a bleeding disorder what should you be thinking?
coagulation-type bleeding disorder
107
What are the diseases associated with platelet defects?
```
von Willebrand disease
Bernard Soulier syndrome
Glanzmann thrombastena
Platelet storage pool disorders
Drugs
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
Heparin induced thrombocytopenia (HIT)
```
108
What are the diseases associated with coagulation defects?
```
von Willebrand disease
Hemophilia A
Hemophilia B
Liver disease
Vit K deficiency
Disseminatd intravascular coagulation (DIC)
```
109
What is the most common inherited bleeding disorder (1% of population)?
von willebrand disease
110
What is the defect in von Willebrand disease?
defect of platelet adhesion
111
What kind of symptoms do you get in von Willebrand disease?
combined platelet and coagulation defect so patient presents with both types
112
What are the four main types of von willebrand disease?
Type I
Type II
Type III (severe disorder with no vWF)
Pseudo (platelet type) -abnormal platelet GPIb leading increased binding of vWF
113
Where do you synthesize von Willebrand factor?
in endothelial cells and megakaryocytes
114
Where is von Willebrand factor stored?
in Weibel-Palade bodies of endothelial cells and agranules of megakaryocytes
115
What does von willebrand do?
mediates platelet adhesion by binding GPIb
116
How does von willebrand factor circulate?
as variably sized multimers
117
Von willebrand factor is also called (Blank)
FVIII-related antigen (complexes with FVIII in circulation)
118
vWF activity is referred as (blank) cofactor activity
ristocetin
119
What is the most common type of von willebrand disease?
type I
120
Von Willebrand disease is a (blank) disorder showing reduced amounts of vWF
quantitative
121
What will lab eval of von willebrand disease show?
prolonged PTT and BT
Decreased FVIII
Decreased vWF and activity
122
What kind of defect does type II von willebrand disease have?
qualitative (functional) defect of vWF
123
What are the four subtypes of type II von willebrand disease?
IIa
IIb
IIM- rare defect that prevents vWF binding to GPIb
IIN-rare defect w/ reduced vWF binding to FVIII
124
What is this:
moderately severe disorder (10-15%)
absence of high molecular weight multimers
Type IIa von willebrand disease
125
What Is the lab eval for type IIa von willebrand disease?
PTT slightly prolonged
| Ristocetin cofactor activity decreased
126
What is this:
results from spontaneous binding of vWF to platelets
dereased high molecular weight multimers
do not give DDAVP (profound thrombocytopenia and bleeding)
Lab eval: enhanced ristocetin cofactor activity
Type IIb von willebrand disease
127
What is this:
defect of platelet adhesion
due to decreased platelet GPIb/V/IX
patient clinically manifest with thrombocytopenia and giant platelets
Bernard Soulier Syndrome
128
What are the lab evals of Bernard Soulier syndrome?
PFT: no aggregation w/ ristocetin
| Peripheral smear will show large platelets (unlike vWD)
129
What is this:
Autosomal recessive disorder due to deficient GP IIb/IIIa (fibrinogen receptor)
Platelets lack the PLa1 antigen
Lab eval shows failure to aggregate with all agonists but ristocetin
Glanzmann thrombasthenia
130
What do patients lack in glanzmann thrombasthenia?
platelets lack of PLa1 antigen
131
In the platelet storage pool defects, what are dense granule diseases and what are they?
no second wave of aggregation
- Hermansky-Pudlak
- Chediak-Higashi
- Wiskott-Aldrich
132
In the patelet storage pool defects, what are alpha-granule diseases?
aggregation is blunted with all agents except ADP
| -gray platelet syndrome
133
What are drugs that can cause excessive bleeding?
Aspirin and NSAIDS
134
What does Aspirin and NSAIDS do?
inhibit COX-1 (enzyme involved in TXA2 production)
135
(blank) exerts autocrine platelet stimulation leading to dense granule release and the secondary wave of aggregation
TXA2
136
The aspirin effect is (reversible/irreversible)
irreversible
137
The NSAID effect is (reversible/irreversible)
reversible
138
What drugs are these:
cause inhibition of ADP-mediated platelet activation
-will see blunted platelet aggregation on PFT in response to ADP
Ticlopidine and Clopidogrel
139
What drugs are these:
inhibitors of GP IIb-IIIa (fibrinogen receptor)
-will see impaired aggregation to all agonists except ristocetin on PFT
Abciximab, Eptifibatide, TIrofiban
140
What are some disorders characterized by thrombocytopenia?
Immune thrombocytopenic purpura (ITP)
thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
Heparin induced thrombocytpenia (HIT)
141
What is immune thrombocytopenic purpura (ITP)?
Diagnosis of exclusion: healthy patient with isolated thrombocytopenia with no other obvious cause
142
What is the antigenic target for ITP?
GPIIb
GPIIIa
GP Ib
GP V
143
What is this:
syndrome resulting from widespread formation of microvascular platelet thrombi affecting CNS, kidneys, GI tract other organs
Thrombotic thrombocytopenic purpura (TTP)
144
What are the symptoms of thrombotic thrombocytopenic purpura (TTP)?
Presents with a pentad of symptoms:
- thrombocytopenia
- microangiopathic hemolytic anemia
- neurologic abnormalities
- renal abnormalities
- fever
145
What is this:
usually idiopathic and an isolated event
-antibodies to the enzyme cause a dysfunction
Thrombotic thrombocytopenic purpura (TTP)
146
What is the pathogenesis behind thrombotic throombocytopenic purpura (TTP)?
- acute deficiency of vWF-cleaving metalloprotease (ADAMTS13)
- causes an accumulation of ultra-large vWF multimers which bind platelets and lead to both thrombi in the microvasculature and thrombocytopenia
147
(Blank) is a disorder that usually occurs when an infection in the digestive system produces toxic substances that destroy red blood cells, causing kidney injury.
Hemolytic-uremic syndrome (HUS)
148
What is thrombotic microangriopathy characterized by?
Thrombocytopenia
Acute renal failure
Microangiopathic hemolytic anemia
149
Hemolytic uremic syndrome is a thrombotic (blank)
microangiopathy
150
What is hemolytic uremic syndrome most commonly associated with?
bloody-diarrhea caused by shiga-toxin producing bacteria
151
What is this:
occurs in 1-3% of patients treated with unfractionated heparin for greater than 5 days.
-
Heparin induced thrombocytopenia (HIT)
152
What causes heparin induced thrombocytopenia (HIT)?
an immune mediated disorder caused by IgG antibodies against the complex of heparin and PF4
153
In heparin induced thrombocytopenia (HIT), which is more common bleeding or thrombosis?
thrombosis
| bleeding is rare
154
Why do you get thrombosis in heparin induced thrombocytopenia (HIT)?
due to platelet aggregation and activation of coagulation
155
What are the symptoms of heparin induced thrombocytopenia?
thrombocytopenia
thrombosis
allergic reactions
156
What is hemophilia A due to?
a congenital X-linked recessive deficiency of Factor VIII
157
What does hemophilia A result in?
decreased or absent circulation FVIII resulting in lifelong bleeding
158
In hemophilia A, patients clinically present with what?
delayed bleeding
| joint and muscle bleeding
159
What is the lab evaluation for hemophilia A?
increased PTT
normal platelet count, PT and TT
decreased plasma FVIII assay
160
What is hemophilia B due to?
a congenital X-linked recessive deficiency of factor IX
161
What does hemophilia B result in?
decreased or absent FIX leading to lifelong bleeding
162
What is another name for hemophilia B?
christmas disease
163
Is hemophilia B clinically distinguishable from hemophilia A?
no (use see delayed bleeding and joint and muscle bleeding)
164
What is the lab eval for excessive bleeding?
prolonged PTT
Normal PT, TT
decreased FIX assay
165
WHat is this:
| decreased synthesis of most clotting factors, including fibrinogen
liver disease
166
In liver disease you get chronic (blank) due to impaired clearance of D-dimer
DIC
167
What does the lab eval look like?
Prolonged PT
| prolonged TT
168
(blank) is involve in y-carboxylation of the G1a domains of clotting factors.
Vit K
169
Vit K deficiency leads to impaired production of vit K dependent factors. What are these factors?
```
Factor II
Factor VII
Factor IX
Factor X
Protein C
Protein S
```
170
What causes vit K deficiency?
- hemorrhagic disease of the newborn
- antibiotics
- malabsorption/malnutrion
- warfarin therapy
171
What is this:
| acquired syndrome characterized by the intravascular activation of coagulation
Disseminated intravascular coagulation (DIC)
172
What are the causes of DIC?
```
Endotoxin causing sepsis (most common)
Trauma
Burns
Obstetrical complications
Vascular malformations
Animal venom
Mucin secreting adenocarcinoma
```
173
Explain how DIC happens
- Excess or prolonged exposure to tissue factor
- generalized activation of coag system and thrombin generation
- fibrin formation and fibrinolysis causes microthrombi and consumption of clotting factors and platelets
- no activation of tissue factor pathway inhibitor (due to ongoing exposure to tissue factor)
174
```
What are these:
Hemorrhage
Renal dysfunction
Hepatic dysfunction
Respiratory dysfunction
Shock
CNS dysfunction
Petechiae
Purpura
Skin necrosis
Signs of thrombosis
```
Clinical manifestations of DIC
175
If you suspect DIC, how should your lab evals go?
order coag tests: (platelet count, prothrombin time, fibrinogen, fibrin monomors or degredation products)
Score coag tests-> score greater than 5 compatible with overt DIC repeat scoring daily, less than 5 not affirmative for non-overt DIC repeat next 1-2 days
176
Diffrential diagnosis of thrombophilia depends on the type of (blank)
thrombosis (arterial or venous)
177
What are examples of excessive thrombosis?
- activated protein C resistance (factor V leiden)
- anti-thrombin deficiency
- anti-phospholipid syndrome
- prothrombin variant
- protein C/protien S deficiency
178
What is this:
| inherited autosomal dominant condition responsible for 50% of the cases of hereditary thrombophilia
Activated protein C resistance (APCR)
179
Activated protein C resistance (APCR) is due to a point mutation in the (blank) gene
FV
180
Activated protein C resistance is due to a point mutation in the FV gene that makes what happen?
FV leiden resistant to proteolytic cleavage by APC
181
Heterozygotes for a FV gene mutation have a (blank) increased risk of thrombosis
5-10%
182
What is this:
| autosomal dominant disorder characterized by recurrent venous thrombosis
Anti-thrombin deficiency
183
What happens if you have an anti-thrombin deficiency?
you have no inactivation of factors II, IXA, Xa, XIa, XIIA (so you keep clotting)
184
People with anti-thombin deficiency that are heterozygotes have (blank) increased risk of thrombosis. (Blank) is considered incompatible with life.
5-10
| incompatible
185
What is this:
an autoimmune thrombophilic condition in which patients have circulating antibodies against plasma proteins that bind to phospholipids.
Anti-phospholipid syndrome
186
In anti-phospholipid syndrome. patients have what sort of problems?
recurrent arterial and venous thrombosis
- pregnancy loss
- immune cytopenias
187
In antiphospholipid syndrome, antiphospholipid antibodies are directed toward (bank) (blank). How can you identify the antibodies?
B2 glycoprotein
prothrombin
By which coagulation assays they prolong
- lupus anticoagulant
- anticardiolipin
188
What is primary APL and where do you find it?
Antiphospholipid syndrome in healthy individuals
189
What is secondary APL associated with?
systemic lupus
malignancy
HIV
collagen vascular disease
190
What drugs are associated with secondary APL?
Phenyotoin, quinidine, hydralazine, procainamide, phenothiazines, IFN, cocaine
191
What is this:
| autosomal dominant condition due to a point mutation in the prothrombin gene.
Prothrombin Variant (G20210A)
192
What does the prothrombin variant mutation cause?
enhances prothrombin gene transcription leading to elevated levels of prothrombin
193
What is the second most common cause of inherited thrombophilia?
Prothrombin variant
194
What is this:
| inherited autosomal dominant form with heterozygotes with 5-7 fold increased risk of thrombosis
Protein C/S deficiency
195
The acquired form of Protein C/S deficiency can result from what?
Coumadin therapy
Liver disease
pregnancy
196
Protein C/ S deficiency can either be due to (blank) or (blank) defects
qualitative or quantitative
