1
Q
Where does vWF come from?
A
- Weibel-Palade bodies of endothelial cells
2. alpha-granules of platelets
2
Q
What is thromboxane A2 a derivative of?
A
platelet cyclooxyrgenase
3
Q
What is the most common symptom of primary hemostasis disorders?
A
epistaxis
4
Q
What general type of primary hemostasis disorders get petechiae?
A
quantitative (not seen really in qualitative)
5
Q
Tests for primary hemostasis disorders
A
- platelet couht
- bleeding time
- bone marrow biospy
- blood smear
6
Q
ITP
A
- AI production of IgG against platelet antigens
- Auto Abs are produced by spleen, and spleen eats platelets that are caught by the auto Abs
- decreased platelet count
- normal PT/PTT
- increased megakaryocytic in bone marrow
- initial tx is corticosteroids
- IVIG can raise platelet count so the spleen eats those Abs instead of the ones attached to the platelets (short lived effect)
- splenectomy
7
Q
What is the most common cause of thrombocytopenia in adults? children?
A
ITP in both
- acute form arises in children though
- chronic found in adults
8
Q
What is a common disease associated with ITP?
A
SLE - chronic form of ITP presents typically in women of child bearing age, and often have a secondary condition like lupus
*IgG can pass placenta, and shortly affect the fetus
9
Q
Microangiopathic Hemolytic Anemia
A
- pathology in small BVs
- micro thrombi form, and shear RBCs –> schistocytes
10
Q
What disorders cause Microangiopathic Hemolytic Anemia?
A
- TTP
- HUS
11
Q
What enzyme is decreased in TTP?
A
ADAMTS13 - used to degrade vWF –> abnormal platelet adhesion –> micro thrombi
- decreased enzyme via auto AB
- classic pt. is adult female
12
Q
What causes HUS?
A
- endothelial damage by drugs or infection (e. coli 0157:H7)
- also leads to a problem in ADAMTS13
- classically seen in kids exposed to undercooked beef
13
Q
Clinical findings of TTP and HUS
A
- skin and mucosal bleeding
- microangipathic hemolytic anemia
- fever
- renal insufficiency
- CNS abnormalities
14
Q
What tissues are most affected in TTP and HUS?
A
kidney + CNS
- HUS is mainly renal
- TTP mainly CNS
15
Q
Laboratory findings of TTP and HUS
A
- normal PT/PTT
- anemia with schistocytes
- increased megarkaryocytes in bone marrow
- thrombocytopenia with increased bleeding time
treatment:
- plasmapheresis and corticosteroids
16
Q
Bernard - Soulier Syndrome
A
- GP1b deficiency
- mild thrombocytopenia with enlarged platelets
17
Q
Glanzmann Thrombasthenia
A
- deficiency in GIIb/IIIa
- platelet aggregation is impaired
18
Q
What does aspirin do?
A
irreversibly inactivates cyclooxyrgenase –> lack of TXA2 –> impairs aggregation
19
Q
What can uremia cause?
A
- adhesion and aggregation is impaired
20
Q
Hemophilia A
A
- factor VIII deficiency
- X linked rec or genetic mutation
- increased PTT, normal PT
- normal platelet count/bleeding time
- tx with factor 8
21
Q
Hemophilia B
A
- factor IX
- other than that matches hemophilia A
22
Q
Coagulation factor inhibitor
A
- acquired AB against coagulation factor
- most common is anti factor 8
23
Q
How do you determine b/t hemophilia A and coagulation factor inhibitor?
A
PTT corrects with hemophilia A, and not with CFI because the donated factor 8 from the normal plasma is still inhibited in CFI
*called a mixing study
24
Q
Von Willebrand Disease
A
- genetic defect in vWF (MOST COMMON inherited coagulation disorder)
- qualitative/quantitative defects
- decreased levels of vWF
- present with mild mucosal and skin bleeding
- increased bleeding time + PTT
- normal PT
- abnormal ristocetin
- tx with desmopressin (increased vWF from WP bodies)
25
How is vWF involved with PTT?
it helps stabilize factor 8
*though with disease, doesn't cause clinical problems with secondary hemostasis
26
When do we see vitamin k deficiency?
- newborns
- long term AB therapy
- malabsorption
27
Why can liver failure cause secondary problems?
- decreased production of factors
- decreased activation of fit K by epoxide reductase
*measured via PT
28
Heparin-induced Thrombocytopenia (HIT)
- platele destruction
- platelet fragments activate remaining platelets, which forms thrombosis
- heparin forms a complex with platelet factor 4, and can form IgG Abs
*don't give them caubinin
29
DIC
- pathologic activation of cascade
- micro thrombi formation
- classically bleed form IV sites, mucosal sites...
- almost always secondary to another disease process like sepsis or rattlesnake bite
- decreased platelets + fibringoen
- increased PT/PTT
- elevated fibrin split products (D- dimer) *best
- treated by fixing underlining cause
30
Fibrinolysis
- increased PT/PTT, bleeding time, and fibringogen split products without d dimers
- tx with aminocaproid acid
*clinically looks like DIC
31
What characterizes thrombosis from postmortem clot?
1. lines of Zahn
2. attachment to vessel wall
*seen in thrombus and NOT postmortem clot
32
What are the risk factors for thrombosis?
1. disruption in blood flow
2. endothelial cell damage
3. hyper coag ulable state
33
Why is turbulence bad?
- clotting factors get mixed up with blood, which activates them
- endothelium gets shredded
34
What is the role of PGI2?
- blocks platelet aggregation
- made by endothelial cells*
*also make NO + heparin like molecules (activate anti thrombin 3 --> inactivates thrombin) + tPA + thrombomodulin
35
What causes high levels of homocysteine? what can this cause?
1. vitamin B12 deficiency + cystathionine beta synthase deficiency
2. endothelial damage
36
Protein C/S deficiency
- they should inactivate factors 5 + 8 to shut down cascade
- without them, pt.s are hyper coagulable
- increased risk of warfarin skin necrosis
37
Facto V Leiden
- mutated factor V that can't be cleaved by protein C/S
- excessive coagulation
*most common inherited cause of a hyper coagulative state
38
Prothrombin 20210A
- point mutation in prothrombin gene
- results in increased GE
- promotes thrombus formation
39
What happens to the PTT in pt.s with ATIII deficiency when given heparin?
- does NOT rise because the ATIII isn't around for the heparin to activate
40
Why are OCT involved in hyper coagulable states?
estrogen increases production of coagulation factors
41
What happens to the d dimer in a DVT?
it is elevated
42
What is the difference b/t edema and effusion?
edema - interstitial space
effusion - pleural, peritoneal, pericardial, and joint spaces
*both are abnormal accumulations of fluid
43
What causes edema?
1. decreased oncotic pressure
2. increased intravascular hydrostatic pressure
a. Na/H2O retention
b. congestion
3. increased vascular permeability
4. Lymphatic obstruction
44
What is the difference b/t hyperemia and congestion?
hyperemia - too much blood arriving (physiological; blood goes to site in need like active muscle; regulated by precapillary sphincter)
congestion - not enough blood leaving (pathological; blood pools)
45
How does HF cause edema? effusion?
1. less blood to the kidneys--> they activate RAAS (renal failure) --> more water/Na retained --> increased blood volume/decreases oncotic pressure --> edema
2. HF --> increased capillary hydrostatic pressure --> edema
3. decreased pump acitivty --> back up pulmonary enough circulation (congestion) --> effusion
46
What can cause lower albumin levels? what does this lead to?
1. malnutrition, decreased hepatic synthesis, nephrotic syndrome
2. edema due to decreased osmotic pressure
47
What is commonly associated with HF?
pleural effusion/pulmonary edema because of the close anatomical relationship
48
What is involved with liver failure?
less production of albumin/portal HTN --> decreased oncotic pressure --> ascites/edema
*portal HTN leads to congestion --> the ascites (abdomen is where the blood goes)
49
How can kidney failure cause edema?
1. water/Na retention (like as is seen with HF)
| 2. Nephrotic syndrome (protein is lost in the urine at high rates; due to abnormally permeable glomerular capillaries)
50
Malnourished children may suffer fro what condition that leads to edema?
Kwashiorkor - protein is insufficient from diet
51
Pt. presents with one LE that is 4x the size of the other. What is the dx?
Lymphedema* caused by...
- infection
- inflammation
- trauma
- tumor
- surgery
- malformations
* cause of localized edema
* elephantiasis
52
What is Filariasis?
- helminth infection (wuchereria) that causes extreme lymphedema
53
Transudate vs. Exudate
fluid leakage vs. protein and fluid leakage
| increased Pc vs. increased inter endothelial space
54
Causes of Increases Hydrostatic Pressure
Decreased Venous Return:
- congestive HF
- constrictive pericarditis
- ascites
- venous obstruction/compression (ex. thrombosis, external pressure like a mass, LE inactivity)
Arteriolar Dilation:
- heat
- neurohumoral dysregulation
55
Causes reduced plasma osmotic pressure
- protein losing glomerulopathies
- liver cirrhosis
- malnutrition
- portion losing gastroenteropathy
56
Causes of Lympahtic obstruction
- inflammatory
- post surgical
- post irradiation
- neoplastic
57
Causes of Sodium retention
- excessive salt intake with renal insufficiency
- increases tubular reabsorption of sodium
- renal hypo perfusion
- increases RAAS secretion
58
Causes of Inflammation
- acute, chronic
| - angiogenesis
59
What conditions does chronic congestion lead to?
1. edema
2. hemosiderosis (iron overload disorder resulting in the accumulation of hemosiderin)
3. tissue damage
60
Why do cells closest to the central hepatic vein die off first?
because they are furthest from the oxygenated blood, and the blood can't get to them because the vein is blocked and won't let more in
61
What is the first step in hemostasis?
vasoconstriction - neurogenic factors + endothelin
*goal is to decrease BF (less blood loss), and SA (easier to repair)
62
What are the steps in primary hemostasis?
1. platelet adeshion
2. shape change
3. granular release
4. recruitment
5. Aggregation (plug is formed)
63
How do platelets attach to the endothelium?
the exposed collagen binds to vWF, which then binds to GpIb on the platelet
64
How/why do platelets change shape?
- increases SA
- GpIIb-IIIa change shape to allow fibrinogen links (allows for aggregation)
- thrombin initiates release of ADP (more activation) and thromboxane A2 (more aggregation)
65
How does aspirin work?
inhibits thromboxane A2
66
Glanzmann Thrombasthenia
deficiency of GpIIb-IIIa - can't get enough platelets to aggregate
67
What do we worry about if a pt. presents with a platelet count of under 10,000?
spontaneous intracranial bleeds
68
Thrombocytopenia
1. Mxn
2. Platelet count
3. Platele adhesion
4. Platele aggregation
1. loss or impaired production of paltelets
2. low
3. yes
4. yes
69
Von Willebrand Disease
1. Mxn
2. Platelet count
3. Platele adhesion
4. Platele aggregation
1. deficiency in vWF
2. Normal
3. No
4. Yes
70
Bernard-Soulier Disease
1. Mxn
2. Platelet count
3. Platele adhesion
4. Platele aggregation
1. deficiency in GpIb
2. Normal - low
3. No
4. Yes
71
Glanzmann's Thromboasthenia
1. Mxn
2. Platelet count
3. Platele adhesion
4. Platele aggregation
1. deficiency of GpIIb-IIIa
2. Normal
3. Yes
4. No
72
What is a second name for factor I? II? VIII?
1. Fibrinogen
2. Prothrombin
3. Antihemophilic A factor (AHF)
73
What factors are vitamin K dependent?
2, 7, 9. 10, Protein C/S
*Ca2+ required to activate vit K and to get factor 10 --> 5 (?)
74
What is the purpose of Coumadin?
- blocks formation of active vitamin K
| - helpful in clot formation prevention
75
What is the difference b/t petechiae? purpura? ecchymosis?
a. small
b. larger
c. palpable
*common in platelet dysfunction
76
What is Hemoarthrosis?
- bleeding within the joint
| - seen with factor deficiencies like hemophilia A
77
How do we break up a clot?
- blood flow washes away the activated clotting factors
| - plasmin is activated by TPA, and breaks apart the fibrin
78
What do we see in thrombosis formation triad 1: endothelium activation?
- down regulation of thrombomodulin and activated protein C
| - elaboration of plasminogen activator inhibitors
79
When do we see turbulent blood flow?
- normal bifurcation
- dilated vessels (aneurysm, hemorrhoids)
- internal obstruction
- external compression
- inadequate heart chamber function
80
When do we see hyper coagulability?
- antithrombin (III) deficiency
- protein C/S deficiency
- factor Va increase
- prothrombin increase
81
What are high risk factors for thrombosis?
- bed rest
- MI
- atrial fibrillation
- tissue injury
- cancer
- prosthetic cardiac valves
- disseminated intravascular coagulation
- heparin induced thrombocytopenia
- antiphropholipid ab syndrome
82
What are some lower risk factors for thrombosis?
- cardiomyopathy
- nephrotic syndrome
- hyperestrogenic states
- OTCs
- sickle cell anemia
- smoking
83
What happens with a large saddle emboli? smaller emboli? extremely small emboli?
1. instantly fatal - right sided HF
2. dyspnea
3. typically asymptomatic; resolves on its own
84
Heparin-induced thrombocytopenia
- prothromotic state caused by Abs to PF4-heparin
- exposure to unfracrtionated heparin
- formation of platelet factor 4-heparin complexes
- IgG cross-linking of platelet Fc receptors and PF4- heparin complexes
- platelet activation and aggregation
*leads to necrosis of fingers and toes
MOD
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