haemostasis 5: coagulopathy Flashcards
what are some causes of minor bleeding symptoms?
- easy bruising
- gum bleeding
- frequent nose bleeds
- post-op bleeding
- menorrhagia
- post-partum bleeding
what are the elements of significant bleeding history?
- epistaxis >10mins with compression
- spontaneous cutaneous haemorrhage / bruising
- > 15min bleeding from trivial wounds
- menorrhagia requiring treatment / causing anaemia
- heavy/prolonged/recurrent bleeding after surger/dental extractions
outline the process of haemostatic plug formation
vessel constriction -> unstable platelet plug formation -> stabilisation of plug with fibrin -> dissolution of clot & vessel repair
what are the general mechanisms for abnormal haemostasis?
lack of a specific factor (failure of production (congenital & acquired)
or increased consumption/clearance)
or defective function of a specific factor (genetic defect or acquired defect eg drugs, synthetic defect, inhibition)
what happens in a disorder of primary haemostasis?
platelet plug does not form properly
what can go wrong to cause a disorder of primary haemostasis?
platelets, VWF, vessel wall
what are some causes of thrombocytopenia?
- bone marrow failure eg leukaemia
- B12 deficiency, accelerated clearance eg ITP (Immune Thrombocytopenic Perpura)
- DIC
- pooling and destruction in splenomegaly
what is the mechanism of ITP?
antiplatelet autoantibodies coat platelet -> macrophage removes platelet
what can cause impaired platelet function?
- hereditary absence of glycoproteins or storage granules
- acquired due to drugs eg aspirin
- NSAIDs
- clopidogrel
what are some examples of hereditary platelet defects?
- Glanzmann’s thrombasthenia (GP2b3a)
- Bernard Soulier syndrome (GP1b)
- Storage Pool disease (dense granules)
what is Von Willebrand disease?
hereditary decrease in number (type 1&3) or function (type 2) of VWF
what are the main functions of VWF in haemostasis?
binding to collagen & capturing platelets and stabilising FVIII (if VWF is v low FVIII may be low)
what abnormalities can occur with the vessel wall?
inherited: haemorrhagic telangiectasia/Elhers-Danlos syndrome/other connective tissue disorders
acquired: scurvy, steroid therapy, age-related perpura, vasculitis
how does typical primary haemostasis bleeding present?
- immediate, prolonged bleeding from cuts
- epistaxes
- gum bleeding
- menorrhagia
- easy bruising
- thrombocytopenia -> petechiae
- severe VWD -> haemophilia-like bleeding (due to low FVIII)
how can you test for disorders of primary haemostasis?
- platelet count & platelet morphology
- bleeding time (PFA100), assays of VWF
- clinical observation
what happens in a disorder of secondary haemostasis?
failure of thrombin generation -> hence fibrin formation and so platelet plug is not stabilised meaning that in larger vessels plug just falls apart
what can go wrong to cause a disorder of secondary haemostasis?
- deficiency of coagulation factor production (haemophilia)
acquired: liver disease (reduced production of clotting factors), dilution, anticoagulant drugs
increased consumption: DIC (disseminated intravascular coagulation) - autoantibodies
what deficiency causes haemophilia A?
FVIII
what deficiency causes haemophilia B?
FIX
what chromosome are haemophilia A&B mutations found on?
X
how is VWD inherited?
Type 2&1 AD, type 3 AR
how does typical secondary haemostasis bleeding present?
FVIII & FIX (haemophilia): spontaneous joint & muscle bleeding
FII (prothrombin): lethal
FXI: bleeding after trauma but not spontaneously
FXII: no excess bleeding at all
what is DIC?
unregulated activation of coagulation - clotting factors get consumed and depleted, activation of fibrinolysis depletes fibrinogen, deposition of fibrin in organs causes clots to form, often associated with sepsis & inflammation
how does typical secondary haemostasis bleeding present?
- superficial cuts do not bleed, bruising common but nosebleeds rare
- spontaneous bleeding is deep - into muscles & joints
- bleeding after trauma may be delayed + prolonged, frequently restarts after stopping
how can you test for disorders of coagulation?
- screening tests: prothrombin time (PT), activated partial thromboplastin time (APTT)
- full blood count
- factor assays
- test for inhibitors
what bleeding disorders are not detected by routine clotting tests?
- mild factor deficiencies
- VWD
- platelet disorders
- vessel wall disorders etc
what are some disorders of fibrinolysis?
- antiplasmin deficiency
- drugs eg tPA
- DIC
how can abnormal haemostasis be treated?
- replace missing factors/platelets
- immune destruction (immunosuppression / splenectomy for ITP)
how can factors be replaced?
- plasma
- cryoprecipitate
- factor concentrates
- gene therapy for haemophilia
- novel antibody approaches
what is desmopressin and how does it work?
vasopressin derivative: causes 2-5x rise in VWF-FVIII (releases endogenous stores hence only useful in mild disorders)
what does tranexamic acid do?
inhibits fibrinolysis
