MOD 5 Flashcards
Name 3 reasons why we have pro-thrombotic factors
- stops the skin from bleeding
- healing bone fractures
- prevents fatal hemorrhages
Why are pregnant women at risk for fatal hemorrhages
A blood clot can occur when the placenta detaches during childbirth, can have a thromboembolism which can travel to the lungs
Name 3 things anti-thrombotic factors can prevent
- heart attack
- stroke
- PE
Contrast primary hemostasis vs secondary hemostasis
Primary: platelet plug
Secondary: stabilization of plug with fibrin –> coagulation
Name 4 core components of hemostasis
- vessel walls (vascular endothelial cells)
- platelets
- coagulation
- fibrinolytic system
- -> defects in any of these can lead to too little or too much clotting
Name 3 events following an arterial injury
- Vascular spasm - vasoconstriction limits blood flow to the area
- Platelet plug
- Coagulation
Name 3 steps aiding the formation of a platelet plug
- Endothelial cells secrete von Willebrand factor
- Platelets secrete chemicals and other PDGF to attract other platelets to the area
- Platelet plug held together by insoluble fibrin
Name…
a) 2 things endothelial cells secrete normally to prevent clotting
b) 2 things endothelial cells secrete normally to prevent a platelet plug
a) heparin-like molecule and thrombomodulin
b) prostacyclin and NO
The lifespan of platelets?
7-10 days
The point where intrinsic and extrinsic pathway converge
Factor 10
What is the main regulatory step of the coagulation system and why?
Thrombin Activation as a small amount can amplify a big response…
One molecule of factor 10 could catalyze 1000 molecules of thrombin, 1 ml of blood has enough thrombin to convert all the fibrinogen in the body to fibrin
Name 3 things that assist in turning off the coagulation system
- Antithrombin 3 - serine protease cleaving 10a and thrombin
- Protein C - Vit K dependent zymogen, requires thrombin to bind to thrombomodulin (endothelial receptor) to become a serine protease that can cleave 5a and 8a
Name 3 anticoagulant DRUGS
- Warfarin
- Heparin
- Direct oral anticoagulants
Name 4 reasons why warfarin isn’t the best choice of blood thinner
- Narrow therapeutic window
- Drug diet interactions
- Difficulty to determine the dose - need to administer frequent INR testing and observation
- Not immediate; as a Vit.K antagonist it can only terminate the synthesis of more factors 2,7,9,10, not destroy the ones currently in the body - may need to give heparin for an immediate solution and warfarin will kick in later
Let’s talk heparin,
A) name two types of heparin
B) What is its effect?
C) Is heparin naturally occurring, man-made or both?
A) i. Long chain unfractionated heparin, IV injected - need to keep measuring APTT and adjusting dose to get the right amount
ii. Low molecular weight heparin (LWM) short chain, given according to weight, easier to administer
B) Assists antithrombin III in breaking down the clot
C) Both! It can also be secreted by MAST cells and basophils
Why are cirrhotic people more likely to bleed?
Cirrhotic people have liver damage, therefore the liver cannot process Vit K, therefore the factors 2,7,9,10 aren’t being produced and coagulation issues will arise - patient more likely to bleed
What largely synthesizes alpha 2 macroglobulin and what 3 cells locally secrete it?
The liver, and macrophages, fibroblasts and adrenocortical cells
How would you know if a disorder of coagulation/hemostasis was acquired or inherited?
Inherited diseases present as single gene defects in an otherwise well patient
Acquired diseases present commonly as issues with multiple parts of the coagulation process in patients already systemically ill
What is iatrogenic enhancement?
Enhancement of a process with man administered drugs
What is factor V Leiden
Protein C deficiency, not directly affecting clotting but slows down the process
Name 3 factors affecting (stimulating or inhibiting) the conversion of plasminogen to plasmin, and whether it inhibits or stimulates it
a) alpha 2 macroglobulin antiplasmin (-)
b) Tissue plasminogen factor (+)
c) TPF drugs; can be naturally made: urokinase and T-PA
and man-made: streptokinase
How does factor 8 contribute to a positive feedback cycle?
factor 8 assists factor 9 in cleaving 10-10a, 10a activates antihemophilic factor which encourages more clotting and more factor 8!
What is a common consequence of a bleeding disorder
Hemarthrosis - bleeding into the joint spaces
Treatment for Hemophilia
Recombinant factor 8
What is PT, what does it measure and what test is commonly associated
Prothrombin time measures time of clotting for the extrinsic pathway, the INR test scores you, 1 = normal, above 4-5 = abnormal clotting time (too slow)
What is APTT and what does it measure?
Activated partial thromboplastin time - measures intrinsic pathway speed
Name two diseases of platelets and what they’re clinically called
- Thrombocytosis: abnormal number
2. Thrombocytopenia: abnormal function
How can intravascular coagulation states lead to excessive bleeding?
Using up the clotting factors
What is DIC and what does it stand for?
Disseminated intravascular coagulation:
End-stage as clotting factors have been used up; meaning body has used up the clotting factors faster than they can be consumed –> spontaneous bleeding in organs –> can be fatal and lead to septic shock
Name the 3 factors of Virchow’s Triad
- Vascular stasis - affects veins
- immobilization, varicose veins and obstruction - Vessel wall - affects arteries
- surgery, chemical and inflammation but the major one is atherosclerosis - hypercoagulation of blood - affects arteries and veins
- cancer, thrombophilia and inflammatory diseases
Risk factors for a VTE
age, previous VTE, immobility, pregnancy, the pill, malignancy, obesity, smoking
Risk factors for an arterial thrombosis
atherosclerosis, hypercholesterolemia, hypertension, obesity, smoking, age, diabetes, ethnicity - south asian
Name 3 characteristics of an arterial thrombi
- pale
- granular
- Lines of Zahn in areas with stronger blood flow which creates alternating lines of red cells and thrombus strands
Name 2 effects of arterial thrombosis and 3 for venous thrombosis
Arterial: infarction and ischemia
Venous: congestion, hemorrhage and edema
What are the 4 outcomes of a thrombosis
- propagation: spreading of thrombosis
(distally in arteries and proximally in veins) - attempt at lysis/removal of clot via the fibrinolytic system, can also be therapeutic with warfarin
- Embolism
- Organization: if you survive the body will repair using the growth of fibroblasts and capillary proliferation (similar to granulation tissue). Recanalisation also occurs which is the opening of vessel channels through the thrombus to reestablish blood flow (but usually never complete :( )
What is the effect of a Massive PE and a symptom
Over 60% reduction in blood flow, rapidly fatal
What is the effect of a Major PE and its symptoms
Medium arteries blocked, patient experiences SOB, chest pain, coughing up hemoptysis
What is the effect of a Major PE and its symptoms
Blocking of minor vessels, asymptomatic or some SOB
Define an embolism
Blockage of a blood vessel through a solid, liquid or gas at a distant site from its origin
If a thromboemboli entered the venous system where would it always end up?
The lungs
If a thromboemboli reaches the ___ what will be affected?
a) aorta
b) carotid arteries
c) abdominal aorta
d) spleen
e) coronary arteries
a) the renal and mesenteric systems (pancreas, intestine and colon)
b) the cerebrum - stroke
c) peripherals - gangrene
d) splenic (white) infarction
e) Ischemic heart disease (can also result in an MI, chest pain, chronic congestive heart failure, sudden death from arrhythmia)
One cause of an air emboli
In pregnancy, air can enter the uterine veins
One cause of nitrogen emboli
Deep-sea diving - compression makes nitrogen go into veins
One cause of Fat emboli, and three locations it is likely to travel to
Fracture to a long bone releases yellow marrow into the blood. Heart, lungs and brain
One cause of amniotic fluid emboli
Pregnancy, a small portion can enter the venous system
