Haemostasis, Acquired, ASPHO Flashcards
1
Q
rupture in endothelial lining–> blood exposed to subendothelial protiens, including___ adn ___ ___
A
collagen; tissue factor
2
Q
3 parts of primary hemostasis?
A
subendothelium
plts
vWF
3
Q
2 collagen d/o’s
A
Ehlers Danlos
Osteogenesis Imperfecta
4
Q
how do you dx Ehlers Danlos?
A
on physical exam:
- skin tenting
- hypermobility
- genetic testing
5
Q
osteogenesis imperfecta: characteristics?
A
- easy fractures
- blue sclera
- easy bruising due to collagen defect
6
Q
all coag factors made inside of the liver; which are also made outside, and where else?
A
F5 (megakaryocytes)
F8 (endothelial cells)
F13 (macropahges)
7
Q
where is VWF made?
A
endothelial cells
megakaryocytes
8
Q
which hemostatic factors are normal or high in infancy?
A
fibrinogen (2)= NORMAL
F8: normal-high
VWF: normal-high
all others are low!–> near normal around 6 months
9
Q
shortest half life coag factor? length?
A
F7; 3-6 hours
10
Q
coag factor with longest half life? how long?
A
F13; 10 days
11
Q
1/2 life of F8?
A
8-12 hours
12
Q
1/2life of F9?
A
22 hours
13
Q
contact activating system includes? order? they are called the ___ ___ because they get activated when blood contacts an ___ ___, eg?
A
- Prekallikrein
- HMW kininogen
- Kallikrein
- F12 and activated F12
- F11
PK–> K via HMW kininogen enzyme; K–> F12, which gets activated to F12a, which then–> PK
contact factors
artificial surface
blood entering a tube/blood touching a CVC
14
Q
12->12A–> activates 11–> 11A, and then waht acts as cofactor for activation of 9-> 9A by 11A?
A
8A
15
Q
what is a cofactor for 10a? for what reaction?
A
5A…for reaction for prothrombin (2)-> thrombin (2a)
16
Q
what does thrombin (2a) do?
A
- cleaves fibrinogen (1) to fibrin
- also activates 13-> 13A
17
Q
what does 13a do?
A
catalyzes fibrin-> cross-linked fibrin clot
18
Q
what catalyzes 7-> 7a?
A
tissue factor
19
Q
what does 7a do?
A
catalyzes 10-> 10a
20
Q
among the contact factors, only ___ def is associated with bleeding
A
F11
21
Q
do all pts with F11 def bleed?
A
yes
22
Q
how does the contact activation system link to the complement system?
A
Kallekrein activates C3; F12a activates C1
23
Q
kallekrein activates what 3 things?
A
F12
C3
bradykinin/kinin (inflammation)
24
Q
rupture endothliuem–> ___ becomes available and does what? issue with this? solution?
A
TF, activates circulating F7-> 7a…this cascade only produces a very small amount of thormbin because F8 adn 9 not involved….thrombin initiates a feedback loop! activate 8-> 8a and 5-> 5a, which are the main catalysts of the coag cascade!
25
phsyiological role of 7a outside of the classic cascade? role of f11 here?
7a activates 9-> 9a...not really used! unless situation of ++ trauma or stress! can get activated by thormbin...this is why F11 def pts only really bleed with trauma or surgery
26
TAFI=?
thrombin-activatable fibrinolysis inhibitor
27
role of TAFI?
gets activated by thrombin to inhibit fibrinolysis
28
all the clotting roles of thrombin=2a?
activates Fs 1 (fibrinogen), 5, 8, 11, 13, TAFI-TAFIa, platelets
29
what does thrombomodulin do?
it modulates the effect of thrombin. NEAR the area of endothelial rupture, thrombomodulin converts thrombin=2a from a procoagulant protein to an anticoagulant protein. Thrombin+Thrombomodulin together will activate Protein C--> activated protein C
30
what does activated protein c do?
inhibits 5a and 8a
31
fibrinogen on which chrom?
4
32
genes that encode fibrinogen?
FGA, FGB, FGG to encode Aalpha chain, BBeta chain, gamma chain respectively--> all come together to make fibrin molecule
33
where is fibirnogen's thrombin binding site? what happens when that site gets cleaved by thrombin?
alpha chain...when that's cleaved, it allows for a linkage between the beta and gamma chains...then lose fibrinopeptide b and a--> FIBRIN
34
how does fibrin interact with clot?
binds plts via GPIIbIIIa:) 2b3a
35
fibrinogen is an __ __ ___ --> elevated ___
acute phase reactant; ESR
36
test for fibrinogen def how?
- measure funcitonal fibrinogne via Clauss method
| - elevated PT, PTT, thrombin time will be prolonged when fibrinogen <1g/L
37
2 tests for dysfibrinogenemia?
thrombin time
| fibrinogen antigen to activity ratio
38
how can you test for fibrinogen and dysfibrinogen in prsence of heparin (because thrombin time affected by heparin)
reptilase time
39
test F13 how?
- clot solubility assay (iwth urea or acetic acid)...qualitative test that is normal or not normal...sensitivie for only very low levels of F13, <5%
- chromogenic assay= more sensitive, not as readily available
40
F13 associated iwth __ __ __ can also get __ __ of __ __, just like with ___ __ ___
poor wound healing
delayed separation of umbilical stump
leukocyte adhesion def
41
natural inhibitors of coag? 4
Tissue factor pathway inhibitor
Antithrombin
Protein C
Protein S
42
Tissue factor pathway inhbibitor acts where?
blocks F7-> 7a
43
antithrombin acts where?
acts on 10a and 2a= thrombin
44
Protein Ca acts where?
blocks 5a, 8a
45
protein s acts where?
cofactor for protein Ca to block 5a and 8a
46
where does protein s come from
secreted from endothelial cells
47
what lyses the clot? where does it come from?
TPA= tissue plasminogen activator; endothelial cells
48
PAI-1 does what?
plasminogen activator inhibitor -1; blocks TPA
49
heparin-sulfate does what?
works with antithrombin to inhibit thrombin and 10A
50
plasminogen--> ? what 2 enzymes can mediate this?
plasmin; tissue plasminogen activator= tPA or urine plasminogen activator= uPA=urokinase
51
tpa is found where?
blood, saliva, GI secretions
52
urokinase found where?
urine
53
plasmin does what?
dissolves fibrin clot-->fibrin split products, d-dimer
54
what inhibitors tpa?
PAI-1
55
what inhibitrs plasmin?
alpha2-antiplasmin
56
waht does TAFIa do?
inhibits plasmin's ability to lyse a clot
57
fibrinolysis increased in what 3 situations?
- DIC
- venous thrombosis
- liver disease
58
issues with the fibrinolytic system where you would expect to get thrombosis?
plasmin def, tpa def
59
fibrinolytic inhibitors...defs--> bleeding?
PAI-1 deficiency
| -alpha 2-antiplasmin deficiency
60
fibrinolytic drug?
tPA
61
2 uses for tPA?
- tx of arterial, venous clots
| - used to tx CVC lumen occlusions
62
two antifibrinolytic drugs? what are analogs of? how do they work?
epsilon-aminocaproic acid and TXA; analogs of lysine; they block plasmin's binding site for fibrin
63
why doesn't f13 prolong PTT, PT?
these assays don't require fibrin to be crosslinked..just generated!
64
thrombin time is abnormal in waht?
hypofibrinogenmia
afibrinogenemia
dysfibrinogenemia
65
If PTT but not PT prolonged, otehr than Defs in 8,9,11,12 ddx? 4
prekalekrein def
HMW K def
circulating anticoagulant
heparin effect
66
PT and PTT prolonged: other than liver disease, DIC, fibrinogen issue, vit k def, ddx? 3
warfarin
heparin effect
circulating anticoagulant
67
vit k sources?
diet
| gut flora syntehsizes vit k too
68
how does vit k acivate 2, 7, 9, 10?
vit k--> vit k hydroxyquinone via vit k epoxide reductase...vit k hydroxyquinone then adds a carboxyl group at gamma position to fs 2,7,9,10 via vit k gamma-glutamyl carboxylase
69
test you can do for vit k def?
PIVKA= proteins induced in vitamin k absence..comes back really high if vit k def!
70
how does warfarin work?
inhibits vit k epoxide reductase, which is needed for converting vit k epoxide-> vit k and for vitk -> Vitk vit k hydroxyquinone, which activates the coag factors
71
how many days does it take for warfarin to become therapetuic?
5-7 days
72
what if you have an early rise in INR before 5-7 days?
this is probably just due to drop in factor 7...however, takes much longer for f10 to drop so don't stop heparin yet...need 5-7 days
73
warfarin should alwasy be overlapped with another anticoagulant until INR is therapeutic for __ ___days
2 consecutive
74
1 possible complication of warfarin use other than bleeding? why?
skin necrosis; early drop in protein C after warfarin starts
75
effects of ddavp? (3)
- increases VWF
- increases F8 (probably due to increased VWF)
- increases tPA release
76
bleeding not used anymore but tests what?
primary hemostasis
77
PT, PTT, TT go into what kind of tube?
blue top tube= citrate tube
78
PT, PTT, TT sample relies on proper ratio of ___ to ___ (__:__)
plasma to citrate; 9:1
79
what can lead to artifacts in PT, PTT, TT? 5
- tube not properly filled--> little plasma--> falsely high results
- pateint with polycytemia= little plasma--> falsely high
- severe anemia= too much plasma--> falsely low (normal) results
- not processed false enough (temp issue)--> falsely high
- difficult draw--> clotting starts too early--> false elevation
- heparin in sample--> false elevation
80
3 heme related acute phase reactants?
fibrinogen
f8
vwf
81
how to DIC work?
inciting event--> activation of coagulation via circulating tissue factor--> consumption of clotting factors and plts (-> bleeding) AND consumption of anticoagulant clotting factors + disurption of endothelial anticoagulant surface--> thrombosis--> fibrinolysis
82
4 causes of DIC?
- sepsis
- kasabach merrit syndrome
- malig, eg APML
- Trauma, eg burns
- severe hemolysis
- severe protein c deficiency
83
what is purpura fulminans?
possible presentation of DIC; severe skin necrosis due to microvascular thrombus, acute onset
84
clinical features of DIC?
- bleeding/bruising/petechiae
- purpura fulminans, organ dysfucntion due to clots
- hemolytic anemia
85
5 lab findings in DIC?
```
high INR
high PTT
low fibirnogen
low plts
elevated d-dimer
elevated fibrin degrationi products
elevated fibrinopeptide A and B
decreased prot C, S, antithrombin
```
86
Neonates are physioloigclaly deficient in what 3 things? how does this related to DIC?
protein C
protein S
AT
impairs protective mechanism for DIC
87
DIC tx?
- tx underlying disease!!!!
- plt transfusion not generally indicated due to risk for increased thrombosis
- FFP (balance of pro-clotting and anti-clotting factors), but no evidence that it affects outcome
- cryo for low fibrinogen if bleeding occurs..no clear evidence of benefit however
88
Does human milk have vitamin K?
has little to none
89
vit k def bleeding in newborn: 3 types and timing?
early: first 24 hours
classical 2-7 days
late 1-6 mos, even later
90
cause of early vit k def bleeding?
maternal drugs: warfarin, anticonvulsants
91
risk factor for classical vit k def bleeding?
none (all babies at risk)
92
risk factors for late vit k def bleeding? 3
CF, liver disease, chronic antibiotic use
93
tx if infant has ICH secondary to vit k def?
Prothrombin complex conetrates immediately, also vit k
94
3 reaosns why liver disease--> bleeding?
most factors made in liver; low plts due to hypersplenism, hyperfibrinolysis due to increased tPA release from endohtelial cells
95
which organ clears d-dimers?
liver...in liver disease, d-dimers will be high
96
2 specific factor inhibitors and cause?
f8 inhibitor: secondary to autoabs
| f5 inhibitor secondary to exposure to bovine thrombin
97
can f8 autoabs in mom be transplacentally passed to baby?
yes
98
mother can passively transfer lupus Ac to baby...can often lead to which type of thrombosis?
Renal vein thrombosis
99
major cuase of LAC?
viral infection
100
LACs tend to be ___ and ___
asyptomatic and transient
101
rarely, pts with LAC also have acquired what?
hypoprothrombinemia...acquired loss of F2 due to increased clearance..."lupus anticoagulant hypoprothrombinemia syndorme"
102
lupus anticoaguant assay AKA?
dilute Russel's viper venom time
103
how does dRVVT work?
2 steps:
1-run teh dRVVT on patient sample..if abnormal, proceed to confirm with step 2
2- re-run, but with exogenous exogenous phospholipid, which should CORRECT teh abnormality seen
104
what's an abnormal dRVVT result?
screening:confirmatory test >1.2
105
how to manage LAC?
repeat assay in 6-12 weeks...no specific therapy indicated; observation
106
tx for lupus anticoagulant hypoprothrombinemia sndrome?
replace prothrombin with PCC for bleeding...observation= usually transient
