Hemostasis, Hemorrhagic disorders and thrombosis Flashcards
Single blood supply vs dual blood supply, which one has what kind of infarct?
single = white
dual = red
What does Thrombin do?
1) what factor is it again?
2) what does it do?
2A
convert fibrinogen to fibrin at the last step of the cascade
activates platelets
activate receptors on inflammatory cells and endothelium
Someone presents with a swollen leg, but not the other. After a blood culture you notice an elevation of IgE. What is your diagnosis?
what is it the most common thing?
Filariasis – helminths infection (Wuchereria)
it’s the most common round worm infection
thrombocytopenia
1) what is the mechanism
2) what is the platelet count like
3) is there platelet adhesion?
4) is there platelet aggregation?
Loss or impaired production of platelets
Low
Yes
Yes
You wan’t to stop someone from clotting too much, what are you going to give them?
additionally, these people can also overdose on this during suicides
what physiologically happens?
aspirin.
no platelet aggregation
Glanzmann’s Thrombasthenia:
1) what is the mechanism
2) what is the platelet count like
3) is there platelet adhesion?
4) is there platelet aggregation?
Abnormal GpIIb-IIIa
Normal
Yes
No
What kind of thrombi is associated with strokes?
what about heart attacks?
white thrombi
why are our lungs edematous in heart failure?
as your left ventricle stops pumping, there’s a congestion happening.
immediately upstream of the left chamber is the lungs! so pulmonary circulation is congestion
so they start leaking fluid into the pleural parenchyma and the pleural space?
when would alterations in blood flow occur that can result in higher risk of thrombosis? (5 things)
1) when could this occur normally? what can it lead to?
2) what can this #1 lead to?
3) what are 2 pathological region?
4) what about the heart, what can happen after a heart attack?
5) what about someone with generalized heart problems?
Normal bifurcations
internal obstruction (atherosclerotic plaque formation)
Dilated vessels / aneurysm or hemorrhoids.. hemorrhoids are dilated static vascular channels.
external compression –> if we have a heart attack, the myocardial wall doesn’t contract.. this coronary artery is pushed against by dead myocardium –> obstruct
AFIB –> it just kind of vibrates a little bit rather than full on contract so you can have an increased risk of thrombosis
What are the three factors influencing infarcts?
explain each
anatomy of vascular supply –> availability of alternative blood supply is the most important determinant if occlusion will cause damage (single or dual blood supply).. single = usually tissue death, dual = less likely for infarction
rate of occlusion –> slow developing are less likely for infarction because of collateral pathways for perfusion form.
tissue vulnerability to hypoxia –> neurons undergo irreversible damage in 3-4 minutes. myocardial cells –> 20-30 mn.
when do you think that someone has a primary hypercoaguable problem?
they have an initial event: DVT, PE, they’re young, strong family history
What are the hallmarks related to heart failure and edema?
soft tissue pitting edema
pulmonary edema
Alterations in blood flow and increased risk of thrombosis?
laminar flow is normal, but it changes to turbulent flow which is very bad
you swish and swirl the blood and factors associated with creating a platelet plug, which results in endothelial damage
What is the name for the fatal pulmonary embolus? why is it fatal?
smaller emboli travel where and present with what?
Saddle Embolus –> super big –> instantaneous right heart failure
more peripherally of the lung, present with SOB
Explain an amniotic fluid embolism
1) what happens
2) what does the mother go through?
3) what do you see histologically?
amniotic fluid is introduced into the mothers blood stream.
anaphylactic reaction –> the mother goes into shock, sudden dyspnea, cyanosis (because it’s foreign components)
squamous cells, hair, fat, mucus in the vessels.
Weible Palade Bodies are found where?
if there’s a tumor and you see it on a slide, what kind of tumor is it?
what do they look like?
what do they release?
endothelial cell
vascular tumor
cucumbers
VWF + P-Selectin
What are the different types of emboli?
Thromboemboli (blood clot)
Fat/marrow emboli
Air emboli
Septic emboli
Amniotic fluid emboli
What is Bernard Soulier Syndrome?
what’s going to be the clinical presentation?
what’s going on under the microscope?
what’s the mnemonic?
Lac of Gp1b receptor on the platelet –> can’t bind to VWF
they have bleeding problems
mild thrombocytopenia with ENLARGED platelets
Bernard Soulier are Big Suckers
What happens if you damage endothelium? what three things tell you that the endothelium has gone from antithrombotic to prothrombotic?
it gets deranged and switches from antithrombotic to prothrombotic
decreases NO activity, increases activation of adhesion molecules
downregulates thrombomodulin (so no protein C, so no anticoagulation)
tPA is inhibited (tissue plasminogen activator) –> this is due to the secretion of Plasminogen activator inhibitors (PAI)
Edema is most likely what kind of fluid?
If you have inflammation, what kind of fluid do you have?
transudate
exudate
You have a normal PTT but an abnormal PT. what factor is affected?
7
Heparin-induced thrombocytopenia
1) What kind of disease process is this? be specific! why is this important?
2) what is the normal process for people with giving heparin?
3) what about abnormal?
4) why is it called thrombocytopenia if that’s not how it works?
hypercoaguability –> Secondary (acquired) physicians do this on accident
1) we give someone heparin, and this binds to PF4… this causes coagulation.. which is normal
HOWEVER in some patients it freaks out their immune system, produces IgG –> starts cross linking it with Fc receptors on platelets –> the platelets release more PF4 –> cycles
so you are cycling and using more and more platelets so excessive coagulation.
you end up having low amounts of platelets because it’s taking it out of the total pool. using everything up
What does the extrinsic pathway involve?
what “time” is it associated with?
why is it called the extrinsic pathway?
7 –> 10 –> thrombin –> fibrinogen –> fibrin clot
Prothrombin (PT)
IT NEEDS to be activated by a factor extrinsic to the blood –> Tissue factor
What is shock?
what are the 5 types?
Body needs more oxygen than it actually can get
cardiogenic shock –> heart isn’t pumping adequately
hypovolemic shock –> not enough volume in your vessels
systemic inflammatory response syndrome –> body is very high maintenance
neurogenic –> decreased vascular resistance due to autonomic disruption
anaphylactic –> IgE mediated decrease in vascular resistance
What is the APCR test?
active protein C resistance test
1) normal patient, add snake venom for it to clot. then you add more and more concentrations of protein C and it takes longer and longer to clot
2) if you do the same with someone with this problem, they will not respond to more and more… it’ll clot
What is the highest risk of acquired (secondary) cause of hypercoaguability that gives people a high risk of thrombosis?
what about women that are under the age of 30?
prolonged bed rest or immobilization
this is why people are giving anticoagulants to patients on bed rest, we don’t have… compression socks, etc.
Oral contraceptive pills –> estrogen increases risk of thrombosis
Some factors of the coagulation pathway are produced in inactive forms. what activates them to active forms and what are they called?
why do they need this?
considering what’s in this pathway, what is vitamin K needed for
2,7,9,10, protein C, protein S
Vitamin K
Vitamin K is needed to make the precursor able to bind calcium, without calcium, those factors are useless –> so these have to use a vitamin K dependent system of carboxylation.
since 2,7,9,10 are all for coagulation, protein C and S are for anticoagulation, so it’s important for both!
What is Virchow’s Triad?
which feed into each other and why?
risk factors for thrombosis
1) endothelial injury
2) hypercoaguability
3) abnormal blood flow
abnormal blood flow and endothelial injury because turbulent flow leads to scraping of the endothelium from the platelet factors
An individual presents with the following symptoms:
mucosal bleeding, coughing up blood, bleeding time is up.
after bloodwork you find they have a deficiency in GP2B3A. what is happening and what is this condition called?
can’t cross link with fibrinogen or aggregate platelets
Glanzmann Thrombasthenia
Why is the healthy endothelium described as a potent antithrombotic mediator?
4 major reasons*****
Endothelium
1) just being there and intact covers up tissue factor (needed to activate extrinsic)
2) inhibits platelets by releasing prostacyclin, NO, and Adenosine diphosphatase (remember ADP is released to increase aggregation of platelets)
3) anticoagulation –> thrombin sees a normal endothelial cell, it’ll bind to the endothelial thrombomodulin… this will create active protein C
4) fibrinolysis via t-PA
Explain White Infarct
1) where does it occur
2) what kind of tissue
3) what kind of circulation and give examples
arterial occlusion in solid organs –>
super dense tissue –> limits the seepage of blood from adjoining capillary beds
end-arterial circulation –> heart, spleen, kidney
We have activation that has happened, what happens during aggregation?
what is the final result
the conformational change in Gp2b-3a complex allows for binding of fibrinogen and cross linking to occur to allow for aggregation
a WEAK platelet plug
Someone is diagnosed with antiphospholipid antibody syndrome
what explains why they are having frequent miscarriages?
what false-positive test would they have that could throw physicians off?
what’s the difference between primary and secondary AAS?
antibody-mediated interference with the growth and differentiation of trophoblasts –> so failure of placentation
syphilis
primary –> presents independent
secondary –> presents with lupus too.
1) what is the most common area for thrombosis?
2) where does it present?
3) what does the pt present with?
Deep Vein Thrombosis –> “DVT”
typically occurs in the lower extremity
1) swelling and redness on the back of the leg, pain even. they can say it feels like they’ve torn a muscle
What are the three fate of thrombi?
Propagation –> thrombus can grow
Emboli
Dissolution (dissolving a clot)
organization/recanalization
Secondary Hemostasis involves what?
what are we forming?
the coagulation cascade!
a fibrin clot –> you’re making sure that the weak plug is stabilized
Why does rate of occlusion matter?
what is more likely to lead to an infarct?
if occlusion occurs slowly enough, COLLATERAL circulation can make up for the vascular obstruction
extremely fast occlusion
If you have a diagnosis of hemosiderosis, what are you going to see on a histological slide?
what are these called?
why are they called this?
how do you know that it’s what it is?
remember, hemosiderosis is red blood cells going through with the edema –> but what happens is you have macrophages ingest these and they become “laden with pigment” –> called “hemosiderin-laden macrophages” –> “heart failure cells”
–> most commonly associated with heart failure
we use an iron stain (makes sense because blood has iron in it)
what is the underlying mechanism or the vast majority of infarcts?
what still possible but less likely? where would these happen? what kind of infarct would this be called?
arterial thrombosis or arterial embolism
venous thrombosis –> more likely in organs with single efferent vein (testis –> testicular torsion, and ovary) –> Red infarct
