what are the causes of natural bleeding? 3
- vascular disorders
- platelet disorders (thrombocytopenia/ defective function)
- defective coagulation (inherited/acquired)
what does the pattern of bleeding depend on? 3
aetiology
- vascular and platelet causes (bleeding into mucous membranes and skin)
- coagulation disorders (bleeding into joints and soft tissues)
describe vascular bleeding? 3
- problems with the vessel wall
- inherited= hereditary hemorrhagic telangiectasia, ehlers-danlos syndrome
- acquired= scurvy, steroids, senile
what is the normal platelet range?
during thrombocytopenia?
when symptoms occur?
- 150-400 x 10^9/L
- plts <150
- plts <10
what are the symptoms of thrombocytopenia? 4
- epistaxis
- GI bleeds
- menorrhagia
- bruising
what are the treatment options for immune thrombocytopenia?4
- steroids and/ or intravenous immunoglobulins
- thromboietin agonists (romiplostim)
- immunosuppression (rituximab)
- splenectomy
describe disorders of platelet function? 3
- platelet count is typically normal
- inherited= many rare diagnoses (glanzmann thrombasthenia)
- acquired= drugs can cause this (aspirin NSAIDs)
describe disorders of coagulation? 3
- due to a defect in the coagulation cascade
- inherited causes (rare)
- acquired causes (common)
name some tests of coagulation? 6
- APTT= activated partial thromboplastin time (assesses the intrinsic pathway)
- PT= prothrombin time (assesses the extrinsic pathway)
- TT= thrombin time (assesses terminal common pathway)
- fibrinogen level
- clotting factor assays (normal level 100%)
- D-dimers= breakdown products of fibrin clot
what are the 2 types of haemophilia?
- haemophilia A (deficiency of factor VIII)
- haemophilia B (deficiency of factor IX)
- both are X linked and only affect males
what are the clinical features of haemophilia? 4
- spontaneous bleeding into joints and muscle
- unexpected post-operative bleeding
- chronic debilitating joint disease
- family history in majority of cases (carrier mums have haemophilia sons) (dads pass genes to carrier daughters)
how do we diagnose haemophilia? 3
- prolonged APTT (tests factors VIII, IX, XI, XII in the intrinsic pathway)
- normal PT (tests factors II, V, VII, X in the extrinsic pathway)
- low factor VIII or IX levels (<1%= severe, 1-5%= moderate, >5%= mild haemophilia)
how can we treat haemophilia? 4
- historic treatments- fractionated human plasma
- this lead to HIV and Hepatitis C infection (and risk of vCJD)
- current treatment- infusions of recombinant factor VIII or factor IX to 50-100& of normal
- prophylactic treatment has revolutionised management of haemophilia patients
what is von Willebrand disease? 4
- autosomal dominant
- von Willebrand factor= large multimeric protein that carries factor VIII in the blood
- vWF also binds platelets to endothelial collagen
- vWD= deficiency of vWF and factor VIII in plasma
- mucocutaneous bleeds, nosebleeds, menorrhagia
name some non inherited causes of increased bleeding? 3
- liver disease
- vitamin K deficiency
- disseminated intravascular coagulation (DIC)
what happens to coagulation in liver disease? 2
- deficient synthesis of clotting proteins
- impaired platelet function and fibrinolysis
what happens to coagulation in a vitamin K deficiency? 2
- infants who do not receive vitamin K at birth
- malabsorption due to jaundice
what happens to coagulation in disseminated intravascular coagulation? 3
- release of pro-coagulant material into circulation
- results in consumption of clotting factors
- causes both bleeding and thrombosis to occur
what are the signs of meningococcal DIC? 3
- prolonged PT, APTT, TT
- low fibrinogen, low platelets
- raised D-dimers or FDPs
what can cause disseminated intravascular coagulation? 3
- cancer
- sepsis
- obstetric disorders
what does iatrogenic mean?
overdose of anticoagulant drugs
name some different types of coagulants? 5
- heparin (used to treat MI, PE, DVT)
- warfarin (used to treat PE, DVT, AF, prosthetic valves)
- DOACs (direct oral anticoagulants)
- direct thrombin inhibitors (dabigatran, argatroban)
- factor Xa inhibitors
what is vitamin K required for?
what is it inhibited by?
how can we become deficient in it? 3
- gamma-carboxylation of factors II, VII, IX, X - -inhibited by warfarin - - malabsorption of vitamin K -biliary obstruction (jaundice) -haemorrhagic disease of the newborn
