bleeding disorders

Question 1

what are the causes of natural bleeding? 3

Answer 1

• vascular disorders
• platelet disorders (thrombocytopenia/ defective function)
• defective coagulation (inherited/acquired)

Question 2

what does the pattern of bleeding depend on? 3

Answer 2

aetiology

• vascular and platelet causes (bleeding into mucous membranes and skin)
• coagulation disorders (bleeding into joints and soft tissues)

Question 3

describe vascular bleeding? 3

Answer 3

• problems with the vessel wall
• inherited= hereditary hemorrhagic telangiectasia, ehlers-danlos syndrome
• acquired= scurvy, steroids, senile

Question 4

what is the normal platelet range?
during thrombocytopenia?
when symptoms occur?

Answer 4

• 150-400 x 10^9/L
• plts <150
• plts <10

Question 5

what are the symptoms of thrombocytopenia? 4

Answer 5

• epistaxis
• GI bleeds
• menorrhagia
• bruising

Question 6

what are the treatment options for immune thrombocytopenia?4

Answer 6

• steroids and/ or intravenous immunoglobulins
• thromboietin agonists (romiplostim)
• immunosuppression (rituximab)
• splenectomy

Question 7

describe disorders of platelet function? 3

Answer 7

• platelet count is typically normal
• inherited= many rare diagnoses (glanzmann thrombasthenia)
• acquired= drugs can cause this (aspirin NSAIDs)

Question 8

describe disorders of coagulation? 3

Answer 8

• due to a defect in the coagulation cascade
• inherited causes (rare)
• acquired causes (common)

Question 9

name some tests of coagulation? 6

Answer 9

• 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

Question 10

what are the 2 types of haemophilia?

Answer 10

• haemophilia A (deficiency of factor VIII)
• haemophilia B (deficiency of factor IX)
• both are X linked and only affect males

Question 11

what are the clinical features of haemophilia? 4

Answer 11

• 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)

Question 12

how do we diagnose haemophilia? 3

Answer 12

• 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)

Question 13

how can we treat haemophilia? 4

Answer 13

• 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

Question 14

what is von Willebrand disease? 4

Answer 14

• 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

Question 15

name some non inherited causes of increased bleeding? 3

Answer 15

• liver disease
• vitamin K deficiency
• disseminated intravascular coagulation (DIC)

Question 16

what happens to coagulation in liver disease? 2

Answer 16

• deficient synthesis of clotting proteins

- impaired platelet function and fibrinolysis

Question 17

what happens to coagulation in a vitamin K deficiency? 2

Answer 17

• infants who do not receive vitamin K at birth

- malabsorption due to jaundice

Question 18

what happens to coagulation in disseminated intravascular coagulation? 3

Answer 18

• release of pro-coagulant material into circulation
• results in consumption of clotting factors
• causes both bleeding and thrombosis to occur

Question 19

what are the signs of meningococcal DIC? 3

Answer 19

• prolonged PT, APTT, TT
• low fibrinogen, low platelets
• raised D-dimers or FDPs

Question 20

what can cause disseminated intravascular coagulation? 3

Answer 20

• cancer
• sepsis
• obstetric disorders

Question 21

what does iatrogenic mean?

Answer 21

overdose of anticoagulant drugs

Question 22

name some different types of coagulants? 5

Answer 22

• 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

Question 23

what is vitamin K required for?
what is it inhibited by?
how can we become deficient in it? 3

Answer 23

- gamma-carboxylation of factors II, VII, IX, X
-
-inhibited by warfarin 
-
- malabsorption of vitamin K 
-biliary obstruction (jaundice)
-haemorrhagic disease of the newborn