haemostasis Flashcards
what is the condition where you lack coagulation factors 8 and 9
haemophilia
wwhat are the characteristics of a normal bleed
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
problem with the ‘characteristics’ of abnormal bleeding
approx. 12% population had easy bleeding
ddoesnt mean that they have a bleeding disorder
name for nosebleed
epistaxis
signs of a bleeding disorder
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
what can be defected in primary haemostasis
collagen vessel wall
vWF
platelets - more complicated
cause of collagen defect
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
what causes the defect in vWF
not assembled in the right way - genetic deficiency - vW disease
what causes the defects with platelets
aspirin and other drugs
thrombocytopenia - inhibit platelet activity
people don’t have enough platelets
describe vWD
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
what is a pattern of bleeding specifically caused by thrombocytopenia
petechiae
when does bleeding start if there is a primary failure (and where)
immediately
gum bleeding
and the previous examples of bleeding
describe petechiae
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
describe the thrombin generaction in haemophiliacs
feeble - not surprising that they bleed
genetics is the most common cause
why does haemophilia cause bleeding
cant make fibrin to stabilise the platelet plug
the primary haemostatic plug is formed but not stabalised so it falls apart - start bleeding again
what are the defects of secondary haemostasis
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
what is disseminated intravascular coagulation
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
consequences of DIC
widespread bleeding from iv lines, bruising, internal
deposition of fibrin in vessels causes organ failure
pattern of bleeding when there are secondary defects
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
what is easy bruising called
ecchymosis
what is haemarthrosis
spontaneous bleeding into the elbow
sign of inflammamation - joint swollen
cause severe joint damage
hallmark of haemophilia
what 2 things cause excess fibrinolysis
excess fibrinolytic factors - plasmin or tPA deficient antifibrinolytic (antiplasmin)
examples of excess fibrinolytic factors
therapeutic admisistration - give tPA to people with strokes to break down clots
some tumours
example of deficient antifibrinolytic
genetic - antiplasmin deficiency
why would there be an anticoagulant excess
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
describe thrombosis
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
what are the effects of the thrombus obstructing the flow of blood
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
effects of a thrombus embolising
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
describe DVT
venous return of blood is obstructed - painful, swollen leg
cause pulmonary embolism
symptoms of pulmonary embolism
shortness of breath
chest pain
sudden death
lung infarction
prevalence of venous thromboembolism
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
relationship between PE and age and DVT and age
both increase with age
PE more steeply
consequences of thromboembolism
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
risk factors for thrombosis
genetic constitution
effect of age, previous events, illnesses and medications
acute stimulus
explain the thrombosis risk
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
what are the factors in virchows triad
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
describe how factors in the blood cause venous thrombosis
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)
describe factor 5 leiden
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
what causes an increase risk of thrombus on the vessel wall
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
what causes an increase risk of thrombus with flow
stasis
eg in surgery, fracture, long haul flight, bed rest
describe the clinical aspects of thrombophilia
increased tendancy to form a thrombus thrombosis at a young age idiopathic thrombosis multiple thrombosis thrombosis whilst anticoagulated
describe the labatory aspects of thrombophilia
identifiable cause of increased risk
AT deficiency
factor 5 leiden
global measures of coagulation deficiency
what conditions causes combined risks for thrombosis
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
describe the risk for post operative VTE
surgery is a major risk
even day surgery is 15-16% higher - lack of mobility, inflammation, underlying disorder
therapy and venous thrombosis
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
prevention of thrombosis
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
hwo do you restore the balance
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
