Coagulopathies Flashcards
1
Q
hemostasis
A
aka coagulation
-the first step in all wound
healing
-limits blood loss by precisely regulated
interactions between components of the blood vessel
wall, platelets, and plasma proteins
2
Q
regulation of hemostasis
A
Ongoing process of formation and dissolving -plasmin system -individual plasma proteins >> C >> S >> Z *keeps you from coagulating too much
3
Q
Unregulated activation of hemostasis
A
can cause
thrombosis and embolism
4
Q
embolism
A
formation of clot in one location which
flows downwards and travels
elsewhere causing thrombosis
5
Q
major steps of hemostasis
A
1) vasoconstriction
2) temporary blockage of a break in the wall of a blood vessel by a platelet plug via platelet adhesion
3) formation of a fibrin clot
6
Q
vasoconstriction in hemostasis
A
1st step in hemostasis in which the blood vessel contracts and spasms -neuromuscular reflex arch that nervous system signals musculayer of blood vessel to contract -clamps down, closes off and slows bleeding
7
Q
platelet adhesion
A
2nd step of hemostasis -Platelets get together, become sticky, aggregate, form a gooey and sticky plug -not an efficient clot to maintain plug in hole
8
Q
formation of a fibrin clot
A
3rd step of hemostasis -Plasma protein as a result in activation (final pathway) in clotting cascade -accomplished by a # of clotting factors
9
Q
fibrin
A
plasma protein/fibers in piece of glaze that form loose mesh, forming in all directions At first loose, mesh tightens and holes close down- forming solid plug -gradually weave and become tighter as clot forms
10
Q
thrombomodulin
A
heparin-like molecule
-Protein made by endothelial
cells of intact blood vessels
-Inhibits thrombin (clotting factor IIa)
*converts II (prothrombin) into IIa (anticoagulant)
-helps protein S activate protein C
*keeps final clot of clotting cascade from forming
11
Q
von Willebrand factor
A
secreted by endothelial cells during injury
- pro-thrombin factor that initiates platelet adhesion
- important for platelet plug formation
12
Q
clotting disorders
A
Disorder of platelets/protein or
clotting problem which is qualitative or quantitative
-based on potential to limit platelet numbers and/or function (primary hemostasis) OR
based on their potential to affect the quantity and/or quality of
clotting factors (secondary hemostasis).
13
Q
primary hemostasis
A
platelet plug/early responder
-after vasoconstriction and seconds after injury of blood vessel, platelets adhere to the blood vessel wall
and aggregate
14
Q
secondary hemostasis
A
plasma coagulation system that
results in fibrin mesh formation—starts within 20 sec of injury
-longer than primary hemostasis
15
Q
thrombocytosis
A
Aka thrombocythemia too many platelets → thrombosis or bleeding Too many platelets = qualitative function as well as quantitative lab: platelet count > 500k
16
Q
Thrombocytopenia
A
too few platelets → bleeding : lab < 100k platelets
Caused by:
– decreased bone marrow production
– increased splenic sequestration
– accelerated destruction of platelets (ITP, TTP)
17
Q
Von Willebrand’s disease
A
platelet disorder involving lack of platelets due to lack of von willebrand factor
- defective adhesion; not really the platelets’ fault
- quantitative and qualitative platelet disorder
18
Q
Physical /Lab findings of Platelet Defects
A
Petechiae, some purpura
• Lab tests: bleeding time and platelet count
• Local measures generally suffice to control bleeding (either high or low)
19
Q
Petechiae
A
Small capillary hemorrhages
forming red dots on skin
20
Q
purpura
A
blending of petechiae to form small purple spots
–formation of purpura together ->
ecchymosis
21
Q
causes of thrombocytosis
A
- an acute reactive process (an APR: recent surgery,
bacterial infection, iron deficiency, or trauma) OR - bone marrow disorder (a
malignancy/cancer in the platelets) -> pt have 0.5% risl/year of progressing to leukemia (Acute myeloid leukemia
22
Q
symptoms of thrombocytosis
A
vasomotor symptoms, thrombosis or bleeding
23
Q
treatments for thrombocytosis
A
– Treat underlying cause if possible
– Antiplatelet medications, unless there is bleeding
– Platelet-pheresis might be needed
– hydroxyurea or anagrelide to lower platelet count in high-risk patients
24
Q
Aspirin 81mg
A
anti-platelet that irreversibly blocks the aggregation of platelets
by interfering with the production of thromboxane
25
splenic sequestration
Gobbling up platelets, storing
them and not allowing them to go
into circulation
-leads to thrombocytopenia
26
Idiopathic thrombocytic purpura
generally autoimmune which leads to accelerated destruction of platelets, eventually leads to thrombocytopenia
- mostly seen in children w/ sudden onset of severe thrombocytopenia following recovery from a viral illness (> 90% recover in 3 – 6 mos)
- detected anti-platelet antibodies
27
risk for spontaneous ICH
```
once platelet count falls below 20,000/microliter
> Endothelial cells always trying-
some clotting necessary in body
> If you cannot generate baseline
clots needed to make
-body may not be able to plug in
brain for normal regeneration of
endothelium
```
28
Pseudo-thrombocytopenia -
occurs when platelets
clump causing the counter to falsely report the platelet
count as low
29
treatment for ITP
only when platelets < 20k
1. high dose steroids
2. IVIG
- pooled IGMg from donors’ mixed plasma Of immunoglobulins Ex) pool of 5 donors mixed together to have plasma-> hope of at least one of these plasmas that there is an antibody to take out ITP
3. Splenectomy is indicated for refractory cases
30
Thrombotic Thrombocytopenic Purpura
```
Sudden cascade of clotting after vessel wall injury -
Thrombocytopenia
Hemolysis
Renal failure
CNS problems (mild to severe;
fluctuant in consciousness, cannot
do long division, seizures, coma)
```
31
exaggerated clotting cascade
```
initiated in TTP
Fibrin clot - fibrin mesh formation
-as it gets tighter and weave gets
pulled together
-red cells try to pass through and
then get lysed
-fibrin mesh closes so tightly that
nothing can pass -> hemolysis
-bleeding is not usually severe
-triggered by plavix, chemo HIV, pregnancy, Lupus
```
32
tetrad of thrombocytopenia in TTP
- thrombocytopenia
- hemolysis
- renal failure
- CNS signs
33
renal failure in TTP
```
Clots in kidney- function
disrupted
-hemolyzing enough- extra HgB in
liver- > cannot handle -> urine
turns pink
Hgb gets stuck in filters of kidney
leading to damage
```
34
triggers leading to TTP
triggered by plavix, chemo HIV, pregnancy, Lupus
35
TTP without brain manifestation
Related to Hemolytic-Uremic Syndrome (HUS), a similar disease seen
in children, which is caused by infection with E. coli O157:H7, Shigella,
or Campylobacter. In this disease, the CNS less commonly affected
36
treatments for TTP
supportive tx -> d/c plavix
1. plasmapheresis
2. exchange transfusion
3. dialysis PRN
37
Von Willebrand Factor
only major clotting factor not made by the liver -> made by vascular endothelial cells and in the bone marrow, by
megakaryocyte
38
functions of vW factor
Binds to and protects inactive factor VIII from spontaneous degradation in the plasma
-thrombogenic (binds to vascular collagen); when expose to damaged vascular endothelial cells -> it uncouples from factor VIII which has the
added advantage of allowing free factor VIII to participate in the clotting cascade
39
deficiency of vWF
Factor VIII degrades rapidly in the plasma
| - leads to a reduction in factor VIII
40
thrombin
responsible for the uncoupling of factor VIII from vWF
| -self perpetual cycle
41
mechanism of free vWF
binds to platelets and makes them “sticky”
> mechanism is
most efficient under high shearing stress
ex) rapid blood flow in narrow blood
vessels as occurs in arterial blood flow
42
Von Willebrand disease
most common hereditary coagulation abnormality
> Can be inherited as either an autosomal dominant or recessive trait
2 types of the disease (type 1 & type 2)
quantitative vs. qualitative
43
type 1 Von Willebrand disease
low levels of normal vW factor and possibly factor VIII (75% of cases)
-quantitative platelet disorder
44
type 2 Von Willebrand disease
normal levels of abnormal vW factor (15-20% of cases) in which platelets are either sticky or not sticky enough
45
type 3 Von Willebrand’s Disease
essentially no vW factor and extremely low factor VIII (very rare;
compare with type 1)
46
acquired vW disease
pt can develop any form of vW disease as result of other pathologies
-Heyde's syndrome: occurs in patients with aortic valve stenosis, leading
to gastrointestinal bleeding
– Hypothyroidism
– SLE
– Malignancies: Wilm’s tumor, lung cancer, lymphomas, P. vera, myeloma
– Drugs: ciprofloxacin, griseofulvin, and valproic acid
47
treatment of vW disease
– vWF/factor VIII concentrate - transfusion
– recombinant von Willebrand factor (r-vWF) man made & not from donors
– desmopressin, which raises vWF (synthetic form of vasopressin/ADH) -> Given for
surgery, major trauma, or other active bleeding
• OCPs for women with menorrhagia
48
desmopressin
synthetic vasopressin which stimulates endothelial cells and megakaryocytes to churn out more vW factor
-given for surgery pre-op and major bleeding such as major trauma
49
coagulation disorders
problem with secondary clotting cascade = fibrin plug
| nothing to do with platelets
50
liver
```
primary site of synthesis of most of the clotting factors as well as the proteins involved in
the fibrinolytic system
-liver makes all anti coagulant factors
AND
-coagulation factors
```
51
fibrinolytic system
body’s natural system of anticoagulation that serves as a constant servo-mechanism offsetting the coagulation cascade
* AKA natural anti-clotting system
- Both of these systems are constantly in motion
ex) when healing, blood clot is dissolved by fibrinolytic system
52
vitamin K-dependent PRO-coagulant factors
```
factors
II (prothrombin)
VII
IX
X
2, 7, 9, 10
*vit K needed to mature activated form*
```
53
vitamin K-dependent ANTI-coagulant factors
proteins C, S, Z
made in liver which interfere with clotting cascade
* if liver does not have enough vit K, it cannot synthesize proteins C, S, Z
54
non-vitamin K-dependent, pro-coagulant factors
factors I (fibrinogen), V, XIII
55
non-vitamin K-dependent anti-coagulant factors
antithrombin-III and plasminogen
56
exceptions that are neither synthesized by liver nor vitamin K dependent
all made by vascular endothelial cells
- vWF (pro-coagulant)
- thrombomodulin (effectively an anticoagulant )
- tPA (tissue plasminogen activator which is an anti-coagulant)
57
factor IV
calcium
- needed to move clotting cascade forwards
- not made by liver
58
vitamin K
important to the activation of factors II,
| VII, IX, X, protein S, protein C, and protein Z (the “ vitamin K dependent factors”)
59
presentation of coagulation factor disorders
Typically manifest as large palpable ecchymoses and
large, spreading, deep soft tissue hematomas
-severe clotting disorder/trauma -> Hemorrhage into synovial joints (hemarthrosis)
ex) pt with coagulation factor disorder will not bleed until post-op due to lack of secondary hemostasis
-cannot make fibrinous clot after platelet plug dissolves
-delayed problem
60
intrinsic pathway
coagulation pathway that is always working in response to damaged endothelium
- depends on activated factors XI & XII (11, 12) and unbound VIII (from vWF) & IX (8, 9)
* AKA aPTT (activated partial thromboplastin)
61
aPTT
measures intrinsic pathway abnormality in activated factors XI & XII (11, 12) and unbound VIII (from vWF) & IX (8, 9)
* think of (P)laying (T)able (T)ennis, which is played indoors
* also tests final common pathway
62
extrinsic pathway
tissue factor pathway that responds to tissue trauma (ex MVC)
1. tissue factor III activates factor VII in presence of phospholipids
- measured by PT
63
PT (protime)
measures abnormality in extrinsic pathway
- the larger the # , the longer the pathway
* think of (P)laying (T)ennis, which is played outdoors
64
PTT
partial thromboplastin phospholipids in presence of factors X & V
* think of (P)laying (T)able (T)ennis, which is played indoors
65
thrombin time
ests for quantitative (fibrinogen deficiency) or qualitative
(dysfunctional fibrinogen) defect
> Thrombin is added to the patient’s plasma
in the lab - time till clot formation begins is noted
66
labs used to evaluate bleeding patient
```
CBC
platelet count
bleeding time
prothromin time
aPTT
thrombin time
```
67
Hemophilia A
Factor VIII Deficiency
most common inherited plasma coagulopathy
-secondary hemostasis coagulopathy that is most common
• X-linked disorder, frequency 1:10,000 males
68
severe cases of hemophilia A
discovered early on in pts due to either:
- hemorrhage after circumcision
- pericranial hematomas from birth trauma
69
mild cases of hemophilia A
sx do not manifest until adolescence
- when pt frequently falls/bumps into things upon learning how to crawl/walk
* Treatment is factor VIII concentrate infusion
70
common sx in Hemophilia A
hemarthrosis
| hematuria
71
Hemophilia B
deficiency in factor IX
-termed Christmas Disease due to pt in 1952 named Stephen Christmas
-Second most common inherited plasma coagulopathy
• X-linked, occurs in 1:100,000 male births
-clinical presentation indistinguishable from Hemophilia A -> diagnosed by assay
72
treatment for Hemophilia B
fresh frozen plasma or factor IX concentrate
| -sometimes gene therapy
73
Factor XI Deficiency
Less severe form of hemophilia that is autosomal recessive (most common in Ashkenazi Jews from
Eastern European)
-discovered in pts that are post-op, have post-traumatic bleeding, or menorrhagia
74
treatment for factor XI deficiency
daily infusion of fresh frozen plasma
when bleeding is active or is anticipated
ex) surgery or childbirth
75
plasmin system
body’s natural system of anti-
coagulation that keeps coagulation in check
-nature's anticoagulants
76
plasmin
aka fibrinolysin
- proteolytic enzyme that lyses fibrin clots
- activated from inactive forrm
77
plasminogen
inactive form of plasmin that is activated by:
-Kallikrein
-Factors XIa & XIIa (intrinsic)
tPA
78
Kallikrein
a serine protease [enzyme] capable of cleaving
peptide bonds in proteins
-activates plasmin
-think of enzyme biting off -ogen from plasminogen
79
tissue plasminogen activator
the same substance used
in the emergency room to reduce the size of brain infarcts
after an acute, occlusive (thrombotic) stroke
80
fibrin degradation products
FDPs aka fibrin split products which results from fibrinolysis
81
D-Dimer
lab test used to measure clotting
* D-Dimer is the most easily detected FSP/FDP
ex) elevated FDPs = increased clotting
82
protein S
activates protein C with the help of
thrombomodulin
-part of nature's anticoagulants
83
protein C
inactivates factors Va and VIIIa
| -part of nature's anticoagulants
84
antithrombin
```
inactivates thrombin (IIa) and Xa
-part of nature's anticoagulants
```
85
tissue factor pathway inhibitor (TFPI)
inactivates VIIa
| - VIIa is the first step of the extrinsic pathway
86
factor V Leiden mutation
when the liver transcribes abnormal gene that codes for factor Va
-still able to participate in common pathway but is insensitive/impervious to protein C
87
anti-platelet drugs
Aspirin
Plavix
Brilinta
88
Warfarin (Coumadin)
-blocks the activity of Vitamin K
-Prothrombin time (PT
or “protime”) is used to monitor the anticoagulant effects of warfarin
-drug is unpredictable
89
Heparin
naturally occurring mixture of varied chain lengths of
glycosaminoglycans (GAGs) derived from porcine intestine
-also
produced by basophils and mast cells
-Activates antithrombin which inactivates IIa & X
*considered an equal opportunity inhibitor
90
low molecular weight heparin
LMWH which is more selective to Factor Xa
- more predictable than Warfarin because it exerts AC effects more on F Xa inhibition
ex) Lovenox (enoxaparin)
