Disorders of heamolysis Flashcards
What is abnormal bleeding define as?
Bleeding symptoms are commo, even in “healthy” people
Many people have easy bruising, mennorhia
BUT the tendency of people with bleeding disorders to have the symptoms are much higher
Also Length-bleed for a longer time, larger bleeding
bleeding history is key-time, setting, resulting conditions (like aneamia)
What are the 3 main ways people can have bleeding disorders?
issues with primary heamostasis, secondary heamostasis or dissolution of clot
What 2 things can go wrong to lead to bleeding?
Lack of specific factor-EITHER fail to produce working one OR Inncreased clearence
Defective function of a specific factor-GENETIC or ACQUIRED (eg: Drugs)
How can platelets bind in primary heamostasis (to each other or vessel)
Either bind VWF that bound collagen with G1p1b OR directly to collagen with G1p1a
then activate and bind each other-G1pIIb/IIIa
How can platelets disorders lead to disorders of primary hemostasis
Platelets:
Low numbers-Thrombocytopenia –Bone marrow failure (Leukemia/b12 deficiency) –Accelerated clearence (autoImmune cytopenia-auto ITP (removal of platelets by macrophages)
Increased pooling of platelets in large spleen (if large spleen)
Function-hereditary absence of glycoproteins (GIp.etc..) OR granules
Acquired due to drugs (aspirin, NSAIDs-wanted or not)
How can VWF lead to disorders of primary heamostasis? What are the types
usually hereditary-decrease of quantity (more common) or function (less binding to collagen/capturing platelets, less FVIII stabilising
rarer acquired due to antibody
Type 1-low VWF
Type 2-abnormal VWF
Type 3-absent VWF
What third issue can lead to disorders of primary heamostasis?
Vessel wall defects-like rare inherited ones (eg: Ehlers danlos + other connective tissue disroders)
Acquired-more common-scurvy, steroid therapy, Ageing, Vasculitis
What are the symptoms of a typical primary heamostasis disorder?
immediate
Prolonged bleeding from cuts Nose blled (epistaxes Gum bleeding, menorrhagia, easy bruising, prolonged bruising after trauma
Petechiae (specific to low platelets)
How can you test for disorders of primary heamostasis?
Platelet counts - platelets morphology (hard to do-need EM)
Bleeding time - (in lab-try and mimic body)
Assays on VWF
Clinical observations
How does the thrombin generation change with time after bleeding?
In healthy-low at very start then PEAKS very fast a few minutes after bleeding (cascade activation)-and then reduced after a bit
with disorders-no peak-small flat increase
How important is any one clotting factor in the cascade?
Theoretically, missing even one could result in a failure of thrombin generation (hence fibrin)
But can be less true via the 2 activation methods
Would be fine for trivial injuries but dangerous for larger bleeds
What are the possible causes of secondary heamostasis disorders?
Hereditary-loss of Factor VIII/IX -Heamophilia A/B–cause spontaneous bleeding of joints and muscles
Lack prothrombin-incompatible with life
(can also lack FXI,XII-but really not bleed as much)
Acquired-much more common Liver disease (failure to produce the factors), people with blood transfusion (if plasma not replaced), Anti-coagulant drugs (Warfarin)
Increased consumption-
Acquired-Disseminated intravascular coagulation (generalised activation of coagulation via TF-consume and depletes coagulation factors-platelets consumed, fibrinolysis depletes fibrinogen=> deposition of fribrin causes organ failure
Autoimmune
What is disseminated intravascular coagulation
Increased consumption-
Acquired-usually caused by sepsis, pregnancy
Disseminated intravascular coagulation (generalised activation of coagulation via TF-consume and depletes coagulation factors-platelets consumed, fibrinolysis depletes fibrinogen=> deposition of fribrin
treat by treating underlying causes
What are the symptoms of people with secondary heamostasis disorders?
dont tend to bleed easily for small cuts-as primary is working
Do tend to bruise a bit easier but not much
BUT spontaneous deep bleeding (joing/muscle)-Heamoarthroma-hallmark
Bleeding after trauma may be delayed and long
Frequently stops and starts again
AVOID intramuscular injections-very bad bleed/bruise
How serious is heamophilia?
quite bad because without treatment, can cause death for small and silly injuries (bitting lips)-
People in less developped countries tend to not have treatment available-die
