abnormalities of haemostasis Flashcards
name 3 minor bleeding symptoms
- easy bruising
- gum bleeding
- menorrhagia in women
what is abnormal bleeding?
- epistaxes (nose bleeds) not stopped by 10 mins of compression
- cutaneous haemorrhage/brusing without apparent trauma
- prolonged bleeding from trivial wounds
- menorrhagia needing treatment or leading to anaemia
- heavy, prolonged bleeding after surgery
what is abnormal bleeding due to?
- lack of specific factor (failure of production, inc. consumption)
- defective function of a factor (genetic or acquired defect)
where can the defects lie in primary haemostasis?
- platelets, vWF or collagen
what causes low numbers of platelets?
- bone marrow failure e.g. B12 def
- accelerated clearance e.g. DIC
- pooling and destruction in splenomegaly
what causes platelets to have an impaired function?
- hereditary absence of glycoproteins/ storage granules
- acquired from drugs e.g. NSAIDs
What is ITP?
immune thrombocytopenia
- anti-platelet antibodies attack platelets
- get engulfed by splenic macrophages
- very common cause of thrombocytopenia
what are the thrombocytopenia causes?
- failure of platelet production by megakaryocytes
- shortened half life of platelets
- inc. pooling and dec. half life of platelets in spleen
what is a hereditary issue in vWD?
- hereditary dec. of quantity and function
- vWF has 2 functions: bind collagen and stabilise F8
- usually hereditary: type 1,3 (def of vWF), type 2 (abnormal function of vWF)
what is an acquired cause of vWD?
- rare
- due to an antibody
what are inherited causes of damage to collagen/vessel wall?
- hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
- other connective tissue disorders
what are the acquired causes of damage to collagen/vessel wall?
- scurvy
- steroid therapy
- ageing (senile purpura)
- vasculitis
what are the typical bleeding patterns in primary haemostasis?
- immediate
- prolonged from cuts and after trauma
- epistaxes
- gum bleeding
- menorrhagia
- easy breeding
what type of bleeding do you get in thrombocytopenia?
- petechia bruising
what type of bleeding do you get in severe vWD?
haemophilia like bleeding
what tests should you do to check primary haemostasis?
- platelet count
- bleeding time
- assays of vWF
- clinical observation
where do the defects lie in secondary haemostasis?
crosslinked fibrin
describe what happens in haemophilia F8
- failure of generation of thrombin burst
- thrombin then converts fibrinogen –> fibrin
- primary platelet plus is enough for small vessel injury
- in larger vessels, plus breaks apart unless stabilised by fibrin
- dec. x-linked fibrin then due to def. of factor production or inc. consumption
describe the hereditary causes of a deficiency of factor production
- F8/9 - Haemophila A/B
- F2 (thrombin) = lethal
- F11 - bleed after trauma but not spontaneously
- F12 - no excess bleeding at all
what are the acquired causes of def. of factor production?
- liver disease
- dilution (transfusions)
- anticoagulant drugs e.g. warfarin
what is an acquired cause of inc. consumption of factors?
DIC (disseminated intravascular coagulation)
- generalised activation of coagulation via TF
- ass/ w/ sepsis, major tissue damage, inflammation
- consumes and depletes coagulation factors, platelets and fibrinogen
- deposition of fibrin in vessels cause organ failure
what is an immune cause of inc. consumption?
auto antibodies
what are the typical patterns of bleeding in secondary haemostasis?
- superficial cuts do not bleed
- bruising common
- nosebleeds rare
- spontaneous bleeding is deep, into muscles and joints
- bleeding after trauma may be delayed but prolonged
- bleeding frequently restarts after stopping
which is the PT pathway? which is the APTT?
PT = extrinsic APTT = intrinsic
what screening tests can be used for secondary haemostasis?
- PT (extrinsic and common pathway defects)
- APTT (activated partial thromboplastin time - intrinsic and common pathway defects)
- FBC
in terms of PT, TT and APTT, what would haemophilia have?
- normal PT and TT
- abnormal APTT as intrinsic pathway affected
what bleeding disorders are not detected by routine clotting tests?
- mild factor def
- vWD
- F13 def
- platelet disorders
- excessive fibrinolysis
- vessel wall disorders
- metabolic disorders
- thrombotic disorders
what is a hereditary defect in fibrinolysis?
anti-plasmin def
what is an acquired defect in fibrinolysis?
- drugs e.g. tPA and bacterial streptokinase
- DIC
what is the genetics behind vWD?
autosomal
dominant - type 1,2
recessive - type 3
how do you treat failure of production/function?
- replace missing factors/platelets
- stop drugs causing it
how do you treat immune destruction?
- immunosuppression e.g. prednisolone
- splenectomy for ITP
how do you treat inc. consumption?
- treat cause
- replace as necessary
explain the principles of factor replacement therapy
- plasma (contains all coagulation factors)
- cryoprecipitate (rich in fibrinogen, F8, vWF, F13
- factor concentrates
- recombinant forms of F8 and F9 avaliable
when would you give DDAVP?
- only when you don’t have enough (not for intrinsic dysfunction)
- vasopressin alternative
- results in 2-5x rise in vWF and F8 by stimulating endothelial cells to release internal stores
- only good for mild disorders
when would you give tranexamic acid?
- slows down breakdown of clots
- inhibits fibrinolysis (competes with tPA)
- widely distributed in body and can cross placenta
