haemostasis 5: coagulopathy

Question 1

what are some causes of minor bleeding symptoms?

Answer 1

• easy bruising
• gum bleeding
• frequent nose bleeds
• post-op bleeding
• menorrhagia
• post-partum bleeding

Question 2

what are the elements of significant bleeding history?

Answer 2

• 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

Question 3

outline the process of haemostatic plug formation

Answer 3

vessel constriction -> unstable platelet plug formation -> stabilisation of plug with fibrin -> dissolution of clot & vessel repair

Question 4

what are the general mechanisms for abnormal haemostasis?

Answer 4

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)

Question 5

what happens in a disorder of primary haemostasis?

Answer 5

platelet plug does not form properly

Question 6

what can go wrong to cause a disorder of primary haemostasis?

Answer 6

platelets, VWF, vessel wall

Question 7

what are some causes of thrombocytopenia?

Answer 7

• bone marrow failure eg leukaemia
• B12 deficiency, accelerated clearance eg ITP (Immune Thrombocytopenic Perpura)
• DIC
• pooling and destruction in splenomegaly

Question 8

what is the mechanism of ITP?

Answer 8

antiplatelet autoantibodies coat platelet -> macrophage removes platelet

Question 9

what can cause impaired platelet function?

Answer 9

• hereditary absence of glycoproteins or storage granules
• acquired due to drugs eg aspirin
• NSAIDs
• clopidogrel

Question 10

what are some examples of hereditary platelet defects?

Answer 10

• Glanzmann’s thrombasthenia (GP2b3a)
• Bernard Soulier syndrome (GP1b)
• Storage Pool disease (dense granules)

Question 11

what is Von Willebrand disease?

Answer 11

hereditary decrease in number (type 1&3) or function (type 2) of VWF

Question 12

what are the main functions of VWF in haemostasis?

Answer 12

binding to collagen & capturing platelets and stabilising FVIII (if VWF is v low FVIII may be low)

Question 13

what abnormalities can occur with the vessel wall?

Answer 13

inherited: haemorrhagic telangiectasia/Elhers-Danlos syndrome/other connective tissue disorders
acquired: scurvy, steroid therapy, age-related perpura, vasculitis

Question 14

how does typical primary haemostasis bleeding present?

Answer 14

• immediate, prolonged bleeding from cuts
• epistaxes
• gum bleeding
• menorrhagia
• easy bruising
• thrombocytopenia -> petechiae
• severe VWD -> haemophilia-like bleeding (due to low FVIII)

Question 15

how can you test for disorders of primary haemostasis?

Answer 15

• platelet count & platelet morphology
• bleeding time (PFA100), assays of VWF
• clinical observation

Question 16

what happens in a disorder of secondary haemostasis?

Answer 16

failure of thrombin generation -> hence fibrin formation and so platelet plug is not stabilised meaning that in larger vessels plug just falls apart

Question 17

what can go wrong to cause a disorder of secondary haemostasis?

Answer 17

• deficiency of coagulation factor production (haemophilia)
  acquired: liver disease (reduced production of clotting factors), dilution, anticoagulant drugs
  increased consumption: DIC (disseminated intravascular coagulation)
• autoantibodies

Question 18

what deficiency causes haemophilia A?

Answer 18

FVIII

Question 19

what deficiency causes haemophilia B?

Answer 19

FIX

Question 20

what chromosome are haemophilia A&B mutations found on?

Answer 20

X

Question 21

how is VWD inherited?

Answer 21

Type 2&1 AD, type 3 AR

Question 22

how does typical secondary haemostasis bleeding present?

Answer 22

FVIII & FIX (haemophilia): spontaneous joint & muscle bleeding
FII (prothrombin): lethal
FXI: bleeding after trauma but not spontaneously
FXII: no excess bleeding at all

Question 23

what is DIC?

Answer 23

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

Question 24

how does typical secondary haemostasis bleeding present?

Answer 24

• 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

Question 25

how can you test for disorders of coagulation?

Answer 25

• screening tests: prothrombin time (PT), activated partial thromboplastin time (APTT)
• full blood count
• factor assays
• test for inhibitors

Question 26

what bleeding disorders are not detected by routine clotting tests?

Answer 26

• mild factor deficiencies
• VWD
• platelet disorders
• vessel wall disorders etc

Question 27

what are some disorders of fibrinolysis?

Answer 27

• antiplasmin deficiency
• drugs eg tPA
• DIC

Question 28

how can abnormal haemostasis be treated?

Answer 28

• replace missing factors/platelets

- immune destruction (immunosuppression / splenectomy for ITP)

Question 29

how can factors be replaced?

Answer 29

• plasma
• cryoprecipitate
• factor concentrates
• gene therapy for haemophilia
• novel antibody approaches

Question 30

what is desmopressin and how does it work?

Answer 30

vasopressin derivative: causes 2-5x rise in VWF-FVIII (releases endogenous stores hence only useful in mild disorders)

Question 31

what does tranexamic acid do?

Answer 31

inhibits fibrinolysis