abnormalities of haemostasis

Question 1

name 3 minor bleeding symptoms

Answer 1

• easy bruising
• gum bleeding
• menorrhagia in women

Question 2

what is abnormal bleeding?

Answer 2

• 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

Question 3

what is abnormal bleeding due to?

Answer 3

• lack of specific factor (failure of production, inc. consumption)
• defective function of a factor (genetic or acquired defect)

Question 4

where can the defects lie in primary haemostasis?

Answer 4

• platelets, vWF or collagen

Question 5

what causes low numbers of platelets?

Answer 5

• bone marrow failure e.g. B12 def
• accelerated clearance e.g. DIC
• pooling and destruction in splenomegaly

Question 6

what causes platelets to have an impaired function?

Answer 6

• hereditary absence of glycoproteins/ storage granules

- acquired from drugs e.g. NSAIDs

Question 7

What is ITP?

Answer 7

immune thrombocytopenia

• anti-platelet antibodies attack platelets
• get engulfed by splenic macrophages
• very common cause of thrombocytopenia

Question 8

what are the thrombocytopenia causes?

Answer 8

• failure of platelet production by megakaryocytes
• shortened half life of platelets
• inc. pooling and dec. half life of platelets in spleen

Question 9

what is a hereditary issue in vWD?

Answer 9

• 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)

Question 10

what is an acquired cause of vWD?

Answer 10

• rare

- due to an antibody

Question 11

what are inherited causes of damage to collagen/vessel wall?

Answer 11

• hereditary haemorrhagic telangiectasia
• Ehlers-Danlos syndrome
• other connective tissue disorders

Question 12

what are the acquired causes of damage to collagen/vessel wall?

Answer 12

• scurvy
• steroid therapy
• ageing (senile purpura)
• vasculitis

Question 13

what are the typical bleeding patterns in primary haemostasis?

Answer 13

• immediate
• prolonged from cuts and after trauma
• epistaxes
• gum bleeding
• menorrhagia
• easy breeding

Question 14

what type of bleeding do you get in thrombocytopenia?

Answer 14

• petechia bruising

Question 15

what type of bleeding do you get in severe vWD?

Answer 15

haemophilia like bleeding

Question 16

what tests should you do to check primary haemostasis?

Answer 16

• platelet count
• bleeding time
• assays of vWF
• clinical observation

Question 17

where do the defects lie in secondary haemostasis?

Answer 17

crosslinked fibrin

Question 18

describe what happens in haemophilia F8

Answer 18

• 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

Question 19

describe the hereditary causes of a deficiency of factor production

Answer 19

• F8/9 - Haemophila A/B
• F2 (thrombin) = lethal
• F11 - bleed after trauma but not spontaneously
• F12 - no excess bleeding at all

Question 20

what are the acquired causes of def. of factor production?

Answer 20

• liver disease
• dilution (transfusions)
• anticoagulant drugs e.g. warfarin

Question 21

what is an acquired cause of inc. consumption of factors?

Answer 21

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

Question 22

what is an immune cause of inc. consumption?

Answer 22

auto antibodies

Question 23

what are the typical patterns of bleeding in secondary haemostasis?

Answer 23

• 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

Question 24

which is the PT pathway? which is the APTT?

Answer 24

PT = extrinsic
APTT = intrinsic

Question 25

what screening tests can be used for secondary haemostasis?

Answer 25

• PT (extrinsic and common pathway defects)
• APTT (activated partial thromboplastin time - intrinsic and common pathway defects)
• FBC

Question 26

in terms of PT, TT and APTT, what would haemophilia have?

Answer 26

• normal PT and TT

- abnormal APTT as intrinsic pathway affected

Question 27

what bleeding disorders are not detected by routine clotting tests?

Answer 27

• mild factor def
• vWD
• F13 def
• platelet disorders
• excessive fibrinolysis
• vessel wall disorders
• metabolic disorders
• thrombotic disorders

Question 28

what is a hereditary defect in fibrinolysis?

Answer 28

anti-plasmin def

Question 29

what is an acquired defect in fibrinolysis?

Answer 29

• drugs e.g. tPA and bacterial streptokinase

- DIC

Question 30

what is the genetics behind vWD?

Answer 30

autosomal
dominant - type 1,2
recessive - type 3

Question 31

how do you treat failure of production/function?

Answer 31

• replace missing factors/platelets

- stop drugs causing it

Question 32

how do you treat immune destruction?

Answer 32

• immunosuppression e.g. prednisolone

- splenectomy for ITP

Question 33

how do you treat inc. consumption?

Answer 33

• treat cause

- replace as necessary

Question 34

explain the principles of factor replacement therapy

Answer 34

• plasma (contains all coagulation factors)
• cryoprecipitate (rich in fibrinogen, F8, vWF, F13
• factor concentrates
• recombinant forms of F8 and F9 avaliable

Question 35

when would you give DDAVP?

Answer 35

• 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

Question 36

when would you give tranexamic acid?

Answer 36

• slows down breakdown of clots
• inhibits fibrinolysis (competes with tPA)
• widely distributed in body and can cross placenta