Hemostasis and Related Disorders Flashcards
(165 cards)
1
Q
What molecule mediates the transient vasoconstriction of primary hemostasis? What cell type releases this molecule?
A
endothelin
endothelial cells
2
Q
What clotting factor binds subendothelial collagen?
A
vWF
3
Q
Platelets bind vWF via what receptor?
A
GpIb
4
Q
What two molecules are contained within Weibel Palade bodies?
A
vWF and P-selectin
5
Q
What is contained in dense granules? What cell type?
A
ADP and calcium
platelets
6
Q
GpIIb/IIIa is upregulated on the surface of platelets by what signal?
A
ADP binding ADP receptor
7
Q
What molecule binds to GpIIb/IIIa?
A
fibrinogen
8
Q
What are petechiae indicative of?
A
thrombocytopenia
9
Q
What is a normal platelet count? Below what level can lead to petechiae?
A
150 - 400
10
Q
What isotype of immunoglobulin is produced during Immune Thrombocytopenia? Against what?
A
IgG
GpIIb/IIIa
11
Q
What cell type produces the Ab during Immune Thrombocytopenia? What organ is this cell located? What organ consumes these RBCs?
A
Plasma cells
spleen
spleen
12
Q
Acute Immune Thrombocytopenia arises in what patient population? After what two happenings?
A
children
viral infection or vaccination
13
Q
Chronic Immune Thrombocytopenia arises in what patient population?
A
women of childbearing age
14
Q
Are any coagulation factors affected during Immune Thrombocytopenia? Why?
A
no . only destruction of GpIIb/IIIa
15
Q
What is the initial treatment of Immune Thrombocytopenia?
A
corticosteroids = initial Tx
16
Q
What two reasons is a splenectomy used as treatment for Immune Thrombocytopenia?
A
removes source of auto-Ab (splenic plasma)
removes site of platelet destruction (splenic macrophages)
17
Q
What is microangiopathic hemolytic anemia?
A
pathological formation of platelet microthrombi in small vessels
18
Q
What cellular happening is seen during MAHA?
A
schistocytes
19
Q
What are the two classic disorders that will produce Microangiopathic Hemolytic Anemia?
A
TTP and HUS
20
Q
Lack of what enzyme causes TTP? What is the normal function of this enzyme?
A
ADAMTS13
cleave vWF
21
Q
What patient population most often develops auto-ADMATS13 Ab’s?
A
adult female
22
Q
What specifc bacterial strain produces HUS? Where is this strain found?
A
E. coli O157:H7
undercooked beef
23
Q
Does HUS cause renal or CNS defects?
A
renal
24
Q
Does TTP cause renal or CNS defects?
A
CNS
25
Are coagulation factors effected during HUS or TTP? What does this mean?
no
PT/PTT = normal
26
What cellular happening is observed during TTP/HUS?
schistocytes
27
What would be observed on a bone marrow biopsy of during TTP/HUS?
schistocytes
28
What are the two treatments of TTP and HUS?
plasmapheresis and corticosteroids
29
What is defective/absent during Bernard-Soulier syndrome? What is impaired?
GpIb
adhesion = impaired
30
What two cellular happenings are seen during during Bernard-Soulier syndrome?
mild thrombocytopenia and enlarged platelets
31
What is defective during Glanzmann thrombasthenia? What is impaired?
GpIIb/IIIa
aggregation = impaired
32
What activates factor VII?
tissue thromboplastin
33
What activates factor XII?
subendothelial collagen
34
Defects in primary homeostasis manifest as what? Where?
skin and mucosal bleeding
nose bleeds (Epistaxis)
35
Defects in secondary homeostasis manifest as what two conditions?
deep tissue bleeding
rebleeding after surgical procedures
36
PT measures which arm of the coagulation cascade?
extrinsic
37
Which clotting factors does PT measure?
I (fibrinogen), two, five, seven and ten
38
PTT measures which arm of the coagulation cascade?
intrinsic
39
What is the mode of inheritance of hemophilia A?
X-linked recessive
40
What are of the coagulation cascade would be effected during hemophilia A?
PTT
41
What coagulation factor is absent during Hemophilia B?
nine
42
What coagulation factor is most likely to develop an autoantibody against it? How would this be diagnosed?
eight
PTT does not correct upon mixing with normal serum
43
Will PTT be corrected if a patient with Hemophilia A is given normal serum?
yes
44
Will PTT be corrected if a patient with Coagulation Factor Inhibitor is given normal serum?
no
45
What two sites will bleed during vWF Disease?
skin and mucosa
46
What branch of the coagulation cascade will vWF Disease effect? Why?
PTT
vWF binds and protects factor eight
47
What drug is used to Dx vWF Disease? What is the MOA of this drug?
Ristocetin
causes vWF to bind GpIb
48
What drug is used to Tx vWF Disease? What is the MOA of this drug?
Desmopressin (DDAVP)
desmopressin causes endothelial cells to release vWF from Weibel-Palade bodies
49
What factors are regenerated by Vitamin K?
two, seven, nine, ten, C and S
50
What branch of the coagulation cascade is used to follow liver failure?
PT
51
What protein do platelets bind during HIT?
PF4
52
What isotype of Ab is involved during HIT?
PF4
53
What pro-coagulant is contained in amniotic fluid?
tissue thromboplastin
54
What two bacteria are the most common causes of septic DIC?
E. coli
N. meningitidis
55
Why does sepsis cause DIC? Why?
endotoxin
influences endothelial cells to make tissue factor
56
What coagulation factor is tissue factor?
III
57
What type of neoplasia can result in DIC? What specific product causes this?
adenocarcinoma
mucin
58
What type of leukemia can cause DIC? Why?
acute promyelocytic leukemia
primary granules
59
What type of bite can cause DIC?
rattlesnake
60
What is the serologic marker for DIC? What is D-Dimer derived from?
D_DIMER
fibrin split products
61
What surgery can cause a disorder of fibrinolysis? Why?
radical prostatectomy
release of urokinase
62
What if the function of urokinase?
activate plasmin
63
Why can liver failure result with a defect in fibrinolysis?
decrease production of α2 anti-plasmin during liver failure
64
Why do errors in fibrinolysis produce an increase in PT and PTT?
plasmin degrades coagulation factors
65
Is the platelet count normal during errors of fibrinolysis?
yes
66
What is the Tx of disorders of fibrinolysis? What is the MOA of this drug?
aminocaproic acid
blocks activation of plasminogen
67
What is the histological pathological finding of thombosis? What are the three components?
Lines of Zahn
platelets and fibrin and RBCs
68
What is Virchows triad?
stasis, endothelial damage, hypercoaguable state
69
What two anti-coagulant molecules are produced by healthy endothelial cells?
PGI2 and NO
70
What fibrinolytic molecule is secreted by a healthy endothelium?
tPA
71
What are the three functions of plasmin?
1. cleave fibrin and fibrinogen
2. destroy coagulation factors
3. block platelet aggregation
72
Does thrombomodulin activate Protein C or does Protein C activate thromobomodulin?
thrombomodulin activates Protein C
73
What coagulation factors are destroyed by Actiated Protein C?
five and eight
74
Deficiency of what vitamin can lead to endothelial damage?
B12
75
Deficiency of what enzyme can result in homocystinuria?
cystathione beta-synthase
76
What are the four defects of CBS deficiency?
vessel thrombosis
dislocated lens
mental retardation
long slender fingers
77
Deficiency of what two proteins predispose to warfarin induced necrosis? Why?
Protein C or Protein S
C and S have shorter half-lifes than two, seven, nine or ten
78
Why does warfarin induced skin necrosis happen?
microthrombi form in vessels
79
Why does Factor V Leiden produce hypercoaguable states?
Factor V lacks cleavage site for APC
80
How is antithrombin deficiency diagnosed?
heparin does not produce increase in PTT
81
What type of drug is associated with an increase in coagulation factor synthesis?
oral contraceptives
82
What is the characteristic histological feature of emboli?
cholesterol clefts
83
Fracture of what type of bones are indicative of a fat embolus?
long bones
84
What are the two gross manifestations of fat emboli?
dyspnea
petechiae on skin over chest
85
Pain from what two locations are characteristic of the bends?
joint and muscle
86
What happens to bones during Caisson disease?
multifocal ischemic necrosis of bone
87
Gestational emboli has what two histological components located inside of it?
squamous cells
keratin
88
What three veins does a PE most often arise from?
femoral, iliac and popliteal
89
What is elevated during a pulmonary embolism?
D-dimer
90
In what part of the heart do systemic emboli usually arise?
left heart
91
What is the first step of primary hemostasis?
transient vasoconstriction
92
What cell synthesizes TXA2 during the clottign cascade?
platelets
93
What organ is the most at risk of bleeding during severe thrombocytopenia?
brain
94
What is a normal bleeding time?
2-7 minutes
95
Which immunoglobulin can cross the placenta?
IgG
96
What cell undergoes hyperplasia during Immune Thrombocytopenia? Where?
Megakaryocytes
on bone marrow biopsy
97
What is the secondary Tx of immune thrombocytopenia?
IV immunoglobulin = secondary
gives splenic macrophages something to chew on rather than IgG anti-GpIIb/IIIa
98
What cell is depleted during Microangiopathic Hemolytic Anemia?
platelets
99
Where is E. coli O157:H7 found?
undercooked hamburger
100
What cell type is damaged that leads to HUS?
endothelial
101
Other than HUS, what can E. coli O157:H7 cause? What specific toxin?
Dysentery
verotoxin
102
What is the mnemonic to remeber the five clinical finding of TTP and HUS?
CRSMF
103
What does the C of CRSMF stand for?
CNS abnormalities
104
What does the R of CRSMF stand for?
renal insufficiency
105
What does the S of CRSMF stand for?
skin and mucosal bleeding
106
What does the M of CRSMF stand for?
Microangiopathic hemolytic uremia
107
What does the F of CRSMF stand for?
Fever
108
Why does TTP and HUS cause skin and mucosal bleeding?
low platelets due to microthrombi formation
109
What myeloid cell would increase in number on a PBS during TTP or HUS?
Megakaryocyte
110
Why are corticosteroids used to treat TTP?
corticosteroids decrease number of antibody producing cells
111
What do platelets look like in Bernard-Soulier syndrome?
enlarged
112
What drug can expose Glanzmann-Thrombasthenia? Why?
Aspirin
lack of TXA2 prevents aggregation
113
What cell contributes the phospholipid surface to the coagulation cascade?
platelets
114
What two locations body does a patient with Hemophilia A present with bleeding?
deep tissue
post-surgical
115
What is the treatment for Hemophilia A?
Recombinant Factor 8
116
How does von Willebrand Disease typically present?
mucosal and skin bleeding
117
What is the most common disorder of coagulation?
vWF disease
118
What coagulation factor does vWF bind to and stabilize?
eight
119
Regarding coagulation, what specific chemical reaction does Vitamin K catalyze?
gamma carboxylation
120
Regarding coagulation, what enzyme is located in the lilver?
Vitamin K epoxide reductase
121
What is the feared result of HIT?
thrombosis
122
What are the two common bleeding sites of DIS?
mucosal surfaces
IV sites
123
Regarding DIC, what in amniotic fluid can activate the coagulation cascade?
tissue thromboplastin
124
What specific type of cancer can cause DIC? Why?
acute promyelocytic leukemia
expansion of platelets and their release of primary granules
125
What type of histological feature is present in Acute Promyelocytic Leukemia?
Auer rods
126
What is the Tx for DIC? What is contained in this?
Cryoprecipitate
fibrinogen
127
What protein inactivates plasmin?
α2 anti-plasmin
128
What factor is used to differentiate a disorder of fibrinolysis vs. DIC?
fibrinolysis disorder = normal platelet count
DIC = low platelets
129
What cell type produces anti-Thrombin III?
endothelial cells
130
What cell type produces tPA?
endothelial
131
What cell type produces thrombomodulin?
endothelial cells
132
What are the three causes of endothelial damage?
atherosclerosis, vasculitis, high serum homocysteine
133
Initial warfarin therapy results in a deficiency of what two anti-coagulants?
Protein C and Protein S
134
What is the mutated version of prothrombin? What mutation is present?
20210A
point mutation
135
What is the key histological fidning of an atherosclerotic embolus?
cholesterol clefts
136
What is the chronic form of a gas embolus?
Caisson Disease
137
What is Caissons disease characterized by?
multifocal ischemic necrosis of bone
138
What is the main complication of chronic pulmonary emboli?
pulmonary hypertension
139
How can anemia present in an individual with already poor coronary vascular function?
angina
140
Where in the GI tract does absorption of ironn occur?
duodenum
141
What is contained within α-granules of platelets?
vWF and fibrinogen
142
Why can oral contraceptives result in a hypercoaguable state?
estrogen promotes synthesis of clotting factors
143
What type of neoplasia can cause iron deficient anemia?
colonic carcinoma
144
What is the most common cause of a decrease in ADAMTS13?
acquired autoantibody
145
Would a disorder of fibrinolysis present with D-dimers? Why or why not?
no
decreased fibrinolysis only--> no degradation of D-dimers to begin with
146
What is lysed during a disorder of fibrinolysis?
fibrinogen
147
What is the most common cause of thrombocytopenia in children and adults?
Immune Thrombocytopenia
148
What is the most common inherited coagulation disorder?
Bernard soulier disease
149
Why does Prothrombin 20210A result in a hyper-coaguable state?
too high of levels of prothrombin
150
Which granule of platelets is vWF contained?
α-granules
151
What is a normal bleeding time?
2-7 minutes
152
Which myeloid cell does uremia interrupt?
platelets
153
Which four clotting factors does the PT follow?
two
five
seven
ten
154
PTT follows all factors except which two?
seven and thirteen
155
Does HIT produce a hypocoaguable or hypercoaguable state?
hyper
156
Which two cytokines are involved during DIC? Via wat mechanism?
TNF and IL1
induce endothelial cells to release tissue factor
157
Does use of lytics increase or decrease BT?
increase
158
Which cell type synthesizes AT III?
endothelial
159
What does plasmin do to platelets?
blocks their aggregation
160
Which cell type secretes tPA?
endothelial
161
What gets transferred from THF to B12? What is the fate of this molecule?
methyl group
homocysteine to methionine
162
Is GpIb involved with adhesion or aggregation?
adhesion
163
Is GpIIb/IIIa involved with adhesion or aggregation?
aggregation
164
What is the key difference between DIC and disorders of fibrinolysis?
no D-dimer with fibrinolysis problems
165
What type of surgery can cause a gas emboli?
laproscopic
