haemostasis

Question 1

what is the condition where you lack coagulation factors 8 and 9

Answer 1

haemophilia

Question 2

wwhat are the characteristics of a normal bleed

Answer 2

spontaneous - eg bruise with no bump, nose bleeds
out of proportion to the trauma/injury - bleeding into joints
unduly prolonged (not faster it just doesn’t stop)
restarts after appearing to stop

Question 3

problem with the ‘characteristics’ of abnormal bleeding

Answer 3

approx. 12% population had easy bleeding

ddoesnt mean that they have a bleeding disorder

Question 4

name for nosebleed

Answer 4

epistaxis

Question 5

signs of a bleeding disorder

Answer 5

epistaxis not stopped after 10mins or need medical attention
cutaneous haemorrhage or bleeding without trauma
bleeding for >15mins from trivial wounds or in the oral cavity
spontaneous bleeding 7days after wound
spontaneous bleeding of GI tract
menorrhagia - requiring treatment or leading to anaemia - not because of structural lesions of the uterus
heavy or prolongued bleeding after surgery or dental extractions

Question 6

what can be defected in primary haemostasis

Answer 6

collagen vessel wall
vWF
platelets - more complicated

Question 7

cause of collagen defect

Answer 7

steroids - break down supporting tissue, make bv more fragile
age - less able to support bv = senile purapura
scurvy - need bit c to cross link fibrinogen
platelets - complicated, so more things can go wrong with them neurafen, volterol?) - inhibit platelet like activity
hereditary - molecules on surface of platelets missing (Gp1B or tP38?)
or people don’t have enough platelets

Question 8

what causes the defect in vWF

Answer 8

not assembled in the right way - genetic deficiency - vW disease

Question 9

what causes the defects with platelets

Answer 9

aspirin and other drugs
thrombocytopenia - inhibit platelet activity
people don’t have enough platelets

Question 10

describe vWD

Answer 10

no vWF so the platelet cant stick
cant bind to collagen because it is going too fast
cant form the plug
nothing for coagulation factor to hold together

Question 11

what is a pattern of bleeding specifically caused by thrombocytopenia

Answer 11

petechiae

Question 12

when does bleeding start if there is a primary failure (and where)

Answer 12

immediately
gum bleeding
and the previous examples of bleeding

Question 13

describe petechiae

Answer 13

distal
back of pallet in mouth
confused with vasculitis and vascular disorder
all the time there are small breaks in the bv - with thrombocytopenia you can’t plug the small holes

Question 14

describe the thrombin generaction in haemophiliacs

Answer 14

feeble - not surprising that they bleed

genetics is the most common cause

Question 15

why does haemophilia cause bleeding

Answer 15

cant make fibrin to stabilise the platelet plug

the primary haemostatic plug is formed but not stabalised so it falls apart - start bleeding again

Question 16

what are the defects of secondary haemostasis

Answer 16

deficiency or defect of coagulation factors - poor thrombin burst = pore thrombin mesh eg
genetic - haemophilia - factor 8 or 9 deficiency
acquired - liver disease, most coagulation factors are made in the liver (cirrhosis) don’t make enough factors, including coagulation ones
- drugs: warfarin inhibit synthesis of factors, others block function
- dilution: volume replacement but coagulation factors are not returned
- consumption: disseminated intravascular coagulation

Question 17

what is disseminated intravascular coagulation

Answer 17

widespread inflammation - sepsis, incompatable blood transfusion, major tissue damage
inf reaction put tissue factor in bv on monocytes and endothelium
generalised activation of coagulation - tissue factor inside the microvasculature
associated with sepsis, major tissue damage and inflammation
consumes and depletes coagulation factor and platelets
activation of fibrinolysis - depletes fibrinogen because all made into fibrin which is deposited into bv - not good - organ dysfunction, chopped as well
platelets used up
antiplatelets degrade the coagulation factors - run out of those too
bleed spontaneously

Question 18

consequences of DIC

Answer 18

widespread bleeding from iv lines, bruising, internal

deposition of fibrin in vessels causes organ failure

Question 19

pattern of bleeding when there are secondary defects

Answer 19

delayed - after primary haemostasis - apparently fine then plug falls apart and you start bleeding
prolonged
deeper - joints and muscles
do the bleeding time test - no bleeding from small cuts
nosebleeds are rare
bleeding after trauma/surgery
after I/m injections

Question 20

what is easy bruising called

Answer 20

ecchymosis

Question 21

what is haemarthrosis

Answer 21

spontaneous bleeding into the elbow
sign of inflammamation - joint swollen
cause severe joint damage
hallmark of haemophilia

Question 22

what 2 things cause excess fibrinolysis

Answer 22

excess fibrinolytic factors - plasmin or tPA 
deficient antifibrinolytic (antiplasmin)

Question 23

examples of excess fibrinolytic factors

Answer 23

therapeutic admisistration - give tPA to people with strokes to break down clots
some tumours

Question 24

example of deficient antifibrinolytic

Answer 24

genetic - antiplasmin deficiency

Question 25

why would there be an anticoagulant excess

Answer 25

eg excess antithrombin due to therapeutic administration eh heparin, thrombin and Xa inhibitors activate antithrombin these drugs are given with good reason but they encourage bleeding

Question 26

describe thrombosis

Answer 26

``` intravascular coagulation inappropriate coagulation coagulation inside a bv coagulation not preceded by bleeding can be venous or arterial caused because too much factor 8 or 11, or too little anticoagulant ```

Question 27

what are the effects of the thrombus obstructing the flow of blood

Answer 27

in artery - MI, stroke, limb ischemia (more serious back flow to tissue, unique blood supply, tissue dies) in vein - causes pain and swelling, there are a few ways for the blood to return

Question 28

effects of a thrombus embolising

Answer 28

venous emboli - in legs, to hear, to pulmonary circulation which is low pressure so not built to take it arterial emboli - usually from the heart, form in left side in atrial fibrillation enter arterial circulation lodge in brain cause cardioembolic stroke, can cause limb ischemia - peripheral, pain in foot

Question 29

describe DVT

Answer 29

venous return of blood is obstructed - painful, swollen leg | cause pulmonary embolism

Question 30

symptoms of pulmonary embolism

Answer 30

shortness of breath chest pain sudden death lung infarction

Question 31

prevalence of venous thromboembolism

Answer 31

1 in 1000-10000 cases a year (10000 younger, 1000 older) incidence doubles with each decade PE cause of 10% of hospital deaths 25k preventable deaths a year

Question 32

relationship between PE and age and DVT and age

Answer 32

both increase with age | PE more steeply

Question 33

consequences of thromboembolism

Answer 33

case mortality 5% 20% recurrence in 1st 2 years, 4% per anum after that thrombophlebitic syndrome - swelling and discomfort doesn't get better, ulcer in leg from disturbance in flow to the heart - sever in 23% people at 2 years, 11% with stockings pulmonary hypertension because the remodelling isn't good for the heart - high mortality rate

Question 34

risk factors for thrombosis

Answer 34

genetic constitution effect of age, previous events, illnesses and medications acute stimulus

Question 35

explain the thrombosis risk

Answer 35

multi causal caused by interacting genetic and acquired risk factors genetic risk - from higher or lower level of thrombin or factor 8 then risk increases with age and you can have acquired risk which could push you over the thrombotic threshold some acquired risks can be removed - eg a broken leg will get better, stop the pill

Question 36

what are the factors in virchows triad

Answer 36

factors in blood - dominant in venous thrombosis factors in the vessel wall - dominant in arterial thrombosis flow 0 complex, contributes to both these can be inherited or acquired

Question 37

describe how factors in the blood cause venous thrombosis

Answer 37

increase in coagulation factors and platelets (factor 8, 2, factor 5 leiden, thrombocytosis - increased platelets) decrease in fibrinolytic factors and anticoagulant proteins (AT, protein C and S)

Question 38

describe factor 5 leiden

Answer 38

5% of people have it - tip in favour of thrombosis polymorphic hereditary of factor 5 factor 5 is resistant to protein C - balance in favour of thrombosis present with thrombosis in white Caucasians, a little in Africa and asia

Question 39

what causes an increase risk of thrombus on the vessel wall

Answer 39

anticoagulant molecules on the surface thrombomodulin, tissue factor, tissue factor inhibitor are all on endothelial cells expression is altered in inflammation - malignancy, infection, immune disorders - down regulate thrombomodulin, increase thrombosis

Question 40

what causes an increase risk of thrombus with flow

Answer 40

stasis | eg in surgery, fracture, long haul flight, bed rest

Question 41

describe the clinical aspects of thrombophilia

Answer 41

``` increased tendancy to form a thrombus thrombosis at a young age idiopathic thrombosis multiple thrombosis thrombosis whilst anticoagulated ```

Question 42

describe the labatory aspects of thrombophilia

Answer 42

identifiable cause of increased risk AT deficiency factor 5 leiden global measures of coagulation deficiency

Question 43

what conditions causes combined risks for thrombosis

Answer 43

pregnancy - coagulation factor increases malignancy - physical obstruction, and inflammation of bv cause increased fibrinogen, factor 8 and vWF surgery inflammatory response reduce mobility and flow

Question 44

describe the risk for post operative VTE

Answer 44

surgery is a major risk | even day surgery is 15-16% higher - lack of mobility, inflammation, underlying disorder

Question 45

therapy and venous thrombosis

Answer 45

treatment: lyse clot - eg tPA high risk of bleeding treatment: limit recurrence, extension or emboli - increased anticoagulant activity, eg heparin, immediate acting, parenteral, restore the haemostatic balance - lower procoagulant factors eg warfarin, oral, slow acting for long term therapy - inhibit procoagulant factors, direct inhibitors Rivaroxaban, Apixaban, Dibigatran (inhibits throimbin) all of these prevent clot and propagation

Question 46

prevention of thrombosis

Answer 46

assess individual and circumstantial risk - acquired, genetic, and circumstantial all patients who enter hospital should have a VTE risk assessment give prophylactic antithrombotic therapy eg heparin and TED stockings - use balance, don't give to haemophiliacs

Question 47

hwo do you restore the balance

Answer 47

just do the things that would tip it the lother way decrease procoagulant factors with warfarin, or give antiplatelet agents (aspirin) or increase anticoag - heparin or drugs that inhibit anticoag activity