Bleeding disorders Flashcards
what is clotting?
a system to repair defects in vessel wall
1’ haemostasis: platelet plug
2’ haemostasis: formation of a fibrin clot
(fibrin degradation- d-dimer)
what is needed for normal haemostasis?
procoagulant proteins anticoagulant proteins fibrinolytic system intact vascular endothelium platelets (APPT)
*thrombin activates most
content of the platelets
no nucleus
procoagulants and anticoagulant
rich in other clotting factors such as VIII and VWF and V. Ca2+, ATP.
central role- initial closure in the vessel wall.
APTT
intrinsic pathway
amplifier of clotting. initiated by PT > amplified by APTT
???happens on the surface of the platelets because it needs phospholipid. (anti phospholipid antibodies?)
clotting test= in lab you ad the phospholipid
in vivo the anti phospholipid are procogaulnt?!?
coagulation factors
synthesised by the liver
sequence of reactions when activated
ends in the deposition of fibrin
network of reaction integrally involved with platelets
APTT
amplifier of clotting
initiated by PT > amplified by APTT
happens on the surface of the platelets because it needs phospholipid. (antiphospholipid antibodies?)
clotting test= in lab you ad the phospholipid
in vivo the antiphospholipid are procoagulant?!?
lab tests
CBC- plt
BT (CT)
PT
PTT
platelet study:
morphology, function, antibody
important coagulation factors (clinically)
factor VIII (haemophilia A)
factor IV (haemophilia B)
VWF
factor VI ('haemophilia C' deficiency-increase risk of bleeding disorder in Jews?)blood vessel injury
constriction (local nitric oxide, the release of epinephrine) reduces the calibre of the blood vessel (reduces surface area but increases the velocity)
platelet aggregation
coagulation cascade
thrombin
activated platelet
fibrinogen to fibrin
activates 9, 11, 5
activates matura anticoagulants.
factor V liden
less sensitive to the deactivation of protein C
generate thrombin for a longer time
site of bleeding
cuteness / mucus membranes (blood vessels capillaries cannot constrict as they have no smooth muscle so usually bleeding is just stopped by platelets)= platelet type bleeding disorder
deep in tissue / joints= dominated by coagulation protein disorders.= haemophilia
duration of bleeding
prolonged bleeding time= platelets
how long has the bleeding disorder been for?
- chronic (congenital)
- acute (late-onset) acquired haemophilia / VWF acquired
precipitating cause
delayed bleeding
surgery/procedures
site of bleeding
cuteness / mucus membranes: bruising, purpura, epistaxis, superficial cuts menorrhaga. (blood vessels capillaries cannot constrict as they have no smooth muscle so usually bleeding is just stopped by platelets)= platelet type bleeding disorder / VWF
deep in tissue / joints= dominated by coagulation protein disorders.= haemophilia
*ask about menorrhea.
systemic illnessess
renal disease liver disease sepsis DIC paraproteins drugs: aspirin, anti platelets, chemotherapy, DOACs
investigations for bleeding disorder
FBC
blood film examination
renal and liver function
(3) coagulation screen= APPT, PTT, fibrinogen
platelet function test including bleeding time.
fibrinogen is needed in active bleeding (polytrauma / major obstetric haemorrhage)
rate-limiting step - if consumed - ran out - bleeding (cannot form a stable clot) *measure using rotam
VWF deficiency
most common inherited cause of abnormal bleeding (haemophilia)
different underyling causes of disease- autosomal dominant.
deficiency, absence or malfunction of glycoprotein- von willerbrand factor.
three types (1-3)
essential for platelet / subendothelial interaction
carrier for factor VIII (shields from being broken down)
quantitative/qualitative defects
PT is normal
APPT is prolonged (depends on VIII level)
- VWF antigen
- VWF activity
augment with desmopressin to release VWF from the cells- boost
VWF deficiency
unusal easy, prolonged or heavy bleeding
Bleeding gums with brushing Nose bleeds (epistaxis) Heavy menstrual bleeding (menorrhagia) Heavy bleeding during surgical operations fhx of heavy bleeding
essential for platelet / subendothelial interaction
carrier for factor VIII (shields from being broken down)
quantitative/qualitative defects
PT is normal
APPT is prolonged (depends on VIII level)
- VWF antigen
- VWF activity
augment with desmopressin to release VWF from the cells- boost (DDAPD)
haemophilia
deep in tissue- swollen knees (haemoarthrosis)
chronic haemophilia arthropathy (waisting of the muscles)
tx: name ? bite antibody bringing factor 5 and 9 = does the job of factor X.
subcutaneous injection
haemophilia A or B
inherited severe bleeding disorders.
Haemophilia A is caused by a deficiency in factor VIII.
Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.
x linked recessive
factor VIII / IX
joint muscle, brain, haematuria, delayed post-op bleeding
prolonged APPT / normal PT
incidental finding on heel prick test
treatment:
minor- desmopressin
tranexamic acid
major- recombinant factor 8
immune thrombocytponeia
purpuric spots
platelet count 15 blood film confirms true low count no platelet clumps normal Hb and WBC ITP occurs in otherwise well
quality of platelets is good but not enough of them. less risk of life-threatening bleeding
- lymphomas (CLL)
- autoimmunity
treatment: suppress the immune system with steroids/ 2’/ splenectomy/ give dugs to increase platlets counts (thrombomimetics)
myelodysplasia
knackered bone marrow
low platelets are part of bone marrow dysfunction (ineffective haemopooies)
blood film- diagnostic with abnormal platelets, RBC, wBC
quantitative and qualitative defect.
hereditary haemorrhagic telangiectasia
predominantly around mouth and alimentary tract
can be in lungs and brains
hereditary haemorrhagic telangiectasia
autosomal dominant
vascular malformation in skin, nasal membranes, gut, lung, brain, liver
more numerous in life
small feeding vessels
predominantly around mouth and alimentary tract
can be in lungs and brains
press- blood goes way, release- sudden blanching through the spiders.
need iron supplements because they bleed so much through their gut.
