Bleeding disorders

Question 1

Haemophilia types?

Answer 1

A and B

Question 2

Haemophilia type A

Answer 2

Defect in F8 gene causing reduced FVIII (haemophilia A)

Question 3

Haemophilia type B

Answer 3

Defect in F9 gene causing reduced FIX (haemophilia B)

Question 4

Haemophilia genetics

Answer 4

Sex-linked recessive inheritance (on X chromosome)

Question 5

Sx of Haemophilia

Answer 5

Coagulation pathway disorder

• Mild or severe bleeding depending on factor level (Soft tissue and joint, CNS, GI bleeds)
• Chronic arthropathy (bleeding in joint leads to inflammation)

Question 6

Mx of haemophilia

Answer 6

• Recombinant factor concentrate (synthetic factor 8 & 9)
• prophylaxis every 2-3 weeks

Question 7

normal roles of vwf?

Answer 7

• VWF mediates PLT adhesion to collagen

- stabilises coagulation Factor VIII in the plasma

Question 8

Mild Von Willebrand disease cause

Answer 8

• Defective primary haemostasis

Question 9

Mild Von Willebrand disease sx

Answer 9

• Epistaxis
• easy bruising
• traumatic skin bleeding

Question 10

Severe Von Willebrand disease cause

Answer 10

• Additional coagulation pathway

- defect due to low FVIII

Question 11

Von Willebrand disease tests?

Answer 11

• Long aPTT in moderate or severe VWD (when FVIII level is low)
• reduced plasma VWF activity
• reduced plasma FVIII activity

Question 12

Management of VWD?

Answer 12

I. Tranexamic acid
II. DDAVP/Desmopressin
III. VWF/FVIII concentrate

Question 13

Tranexamic acid

Answer 13

Reduces clot break-down

antifibrinolytic

Question 14

DDAVP/Desmopressin

Answer 14

• Releases endogenous FVIII and VWF

- only works once, temporary release

Question 15

Bleeding disorders acquired causes

Answer 15

1. Abnormal synthesis
2. Abnormal function
3. Dilution
4. Consumption

Question 16

Potential causes of abnormal synthesis leading to acquired bleeding disorders?

Answer 16

• Liver disease
• Vitamin K deficiency (coagulation factors II, VII, IX, X)
• Warfarin

Question 17

Potential causes of abnormal function leading to acquired bleeding disorders?

Answer 17

• Heparin and direct acting oral anticoagulants*
• Renal failure (platelet dysfunction)
• Anti-platelet drugs

Question 18

Potential causes of dilution leading to acquired bleeding disorders?

Answer 18

• Massive transfusion

* Cardiopulmonary bypass

Question 19

Potential causes of consumption leading to acquired bleeding disorders?

Answer 19

(Thrombotic microangiopathies )
• Disseminated intravascular coagulation*
• Thrombocytopenia in sepsis

Question 20

Liver damage and clotting?

Answer 20

I. ↓Synthesis of most clotting factors, fibrinogen and coagulation regulators
II. ↓PLT number
III. Biliary obstruction gives vit K malabsorption
IV. Hyperfibrinolysis

Question 21

Vit K role?

Answer 21

needed for synthesis of Factors II, VII, IX and X

Question 22

Disseminated intravascular coagulation (DIC) causes

Answer 22

I. Sepsis
II. Major trauma
III. Obstetric emergencies (pre-eclampsia,
amniotic fluid embolism, retained POC)
IV. Advanced malignancy

Question 23

Disseminated intravascular coagulation (DIC) pathophysiology

Answer 23

I. Pro-coagulant stimulus + loss of regulatory pathways –> Widespread activation of coagulation pathway

II. Fibrin/platelet rich
microvascular thrombi and Multiorgan failure

III. Platelet, fibrinogen and
coag factor consumption and bleeding

Question 24

Management of DIC

Answer 24

• Fresh frozen plasma
• Platelet transfusion
• Fibrinogen concentrate or
cryoprecipitate

Question 25

Thrombotic thrombocytopenic purpura (TTP) Sx?

Answer 25

- onset fever, malaise, arthralgia - Bleeding • Variable neurological features • Chest pain • Jaundice + abdo pain

Question 26

Thrombotic thrombocytopenic purpura (TTP) cause?

Answer 26

Caused by anti-ADAMTS13 antibodies

Question 27

Thrombotic thrombocytopenic purpura (TTP) pathology?

Answer 27

anti-ADAMTS13 antibodies-> Reduced proteolysis of VWF -> Circulating ultra-high molecular weight VWF multimers -> Platelet agglutination in ‘high shear’ vessels, microvascular, thrombosis, platelet consumption, mechanical haemolysis

Question 28

Diagnosis of TTP

Answer 28

Blood film is diagnostic: smashed in half | PLT reduced and Hb reduced

Question 29

Mx of TTP?

Answer 29

``` PLASMA EXCHANGE or II. Supportive care • RBC transfusion • Aspirin and LMW heparin • Iv corticosteroids Rituximab ```

Question 30

DVT 1. first investigation? 2. secondary Ix?

Answer 30

1. Wells score for DVT diagnosis 2. I. Score >1= - DVT likely - Doppler USS II. Score 1 or less: - DVT unlikely - D dimer test - Doppler USS if high

Question 31

DVT complications?

Answer 31

Post-thrombotic syndrome: - Chronic swelling and aching - Venous eczema and ulcers

Question 32

PE complication?

Answer 32

``` Chronic thromboembolic pulmonary hypertension (CTPH) ``` - 0.5-5% of treated clots replaced by fibrous tissue - Progressive Pulmonary HTN and RHF

Question 33

3 conditions that increase the risk of DVT?

Answer 33

1. Antithrombin deficiency 2. Factor V Leiden 3. antiphospholipid syndrome

Question 34

Antithrombin deficiency mx

Answer 34

- Long term anticoagulation - short term AT concentrate

Question 35

Factor V Leiden pathology?

Answer 35

Reduces inactivation of Factor V by activated protein C

Question 36

Management of anti phospholipid syndrome?

Answer 36

- If thrombotic, long term anticoagulation (plus antiplatelet agent if arterial thrombosis)

Question 37

Immediate Management of DVT and PE?

Answer 37

- Fast acting anticoagulant minimum 3 months | - (Rivaroxaban or LMW heparin)

Question 38

long term Management of DVT and PE?

Answer 38

anticoagulation: - Rivaroxaban, - warfarin. - LMWH in cancer or pregnancy

Question 39

2 types of Anti-thrombotic drugs

Answer 39

1. Anti-platelet drugs | 2. Anti-coagulant drugs

Question 40

Anti platelet drugs used for?

Answer 40

Treatment/prevention arterial thrombosis | eg ACS

Question 41

Anti coagulant drugs used for?

Answer 41

treatment/prevention venous thrombosis or low pressure vessel thrombosis eg DVT, PE, CVA in AF

Question 42

NICE guidlines for VTE thromboprophylaxis

Answer 42

All patients at risk of VTE should: • Mobilise early • Receive pharmaceutical thromboprophylaxis (eg enoxaparin 40 mg once daily)

Question 43

mech of action of heparin

Answer 43

• Increases activity of natural anticoagulant antithrombin • Inhibits active clotting factors esp. Factors IIa (thrombin) and Xa

Question 44

Route of UF heparin

Answer 44

IV

Question 45

Route of LMW heparin

Answer 45

SC

Question 46

Metabolism of UF heparin

Answer 46

Renal

Question 47

Metabolism of LMW heparin

Answer 47

Renal

Question 48

Half life of UF heparin

Answer 48

1-2hours

Question 49

Half life of LMW heparin

Answer 49

4-6 hours

Question 50

Reversal of UF heparin

Answer 50

Protamine iv 1mg/100 IU heparin in last hr (max 40mg)

Question 51

Reversal of LMW heparin

Answer 51

Protamine iv 1mg/100 IU heparin in last hr (max 40mg)

Question 52

Direct oral anticoagulant (DOAC) example?

Answer 52

rivaroxaban

Question 53

Rivaroxaban mech of action

Answer 53

* Factor Xa inhibitor | * Reduces thrombin generation

Question 54

Rivaroxaban use?

Answer 54

I. VTE prevention after knee/hip replacement II. Stroke prevention in non-valvular AF III. Acute and long term treatment of DVT

Question 55

Rivaroxaban half life?

Answer 55

8 hours

Question 56

Rivaroxaban metabolised by

Answer 56

75% liver metabolised, | 25% renal excreted

Question 57

Rivaroxaban reversal?

Answer 57

Specialist products (APCC, specific reversal agents) for severe bleeding

Question 58

Warfarin mech of action?

Answer 58

Inhibits vitamin K metabolism (factors 2,7,9,10)

Question 59

Warfarin uses?

Answer 59

I. when DOACs are unsafe II. Long term VTE III. Stroke prevention in AF IV. With anti-platelet agent, to prevent arterial thrombosis

Question 60

when are DOACs unsafe

Answer 60

- Mechanical heart valves, - Antiphosphoilipid syndrome, - CKD

Question 61

Warfarin half life

Answer 61

Plasma half life ~36 hours

Question 62

Warfarin metabolised by

Answer 62

liver

Question 63

Warfarin reversal

Answer 63

- Vitamin K if INR >8.0 for mild bleeding | - Vitamin K factor concentrate (eg Octaplex) plus Vit K for severe bleeding