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Flashcards in Haematology Coagulation 2 Deck (76):
1

Haemophilia: Description

Defect in Factors that affect clotting factors downstream

2

Haemophilia A

Defect in F8 gene causing reduced FVIII

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Haemophilia B

Defect in F9 causing reduced FIX

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Haemophilia: Inheritance

Sex Linked – FIND OUT MORE

5

Haemophilia: Clinical features of Haemophilia

Mild provoked bleeding if factor level >5%
Severe spontaneous bleeding if factor level <1%
• Soft tissue and joint bleedings (leads to synovitis) – chronic inflammatory changes
• Life-threatening CNS or GI bleeds
• Chronic arthropathy
• Treatment acquired HCV and HIV

6

Haemophilia: Treatment

Recombinant factor concentrate – personalised prophylaxis regimes to ensure factor levels never drop to ‘severe’ levels

→ Implant venous access device for easier infusions

7

Venous Thrombosis: VTE disease

Formation of fibrin-rich clots in low-pressure venous system
Includes DVT, PR, or thrombosis in axillary/ subclavian/portal. Mesenteric/cerebral veins

8

Venous Thrombosis: Thrombophilia

Increased propensity to VTE
Acquired + genetic risk factors

9

Venous Thrombosis: National burden of VTE

PE
DVT – 25K deaths per year in the UK

Elective Hip and Knee surgery % risk with no prophylaxis:
• 45% Hip
• 60% knee

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Venous Thrombosis:DVT presentation common

Unilateral pain
Swelling
Tenderness
Discolouration

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Venous Thrombosis: DVT presentation rare

Dilated superficial veins
Venous gangrene (v. rare)

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Venous Thrombosis:Note

Size of clot doesn’t relate to symptoms

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Venous Thrombosis: DVT diagnosis

Clinical history
Physical examination
Wells Score (screening) (2+) SEE MORE
D Dimer blood test (screening) – low good/
Confirmatory tests

14

Venous Thrombosis: Confirmatory tests

Doppler ultrasound
(Venography)
CTV/MRV for VTE at unusual

15

Venous Thrombosis: Doppler Ultrasound

Flow (red colour is not visible in the main vein (arrows), indicating lumen filled with thrombosis (SEE image)

16

Pulmonary Embolism: Symptoms


SOB
Cough
(Pleuritic) chest pain
Haemoptysis
Syncope
Palpitations
Sweating

17

Pulmonary Embolism: Diagnosis and results

Wells Score
ECG - Sinus tachycardia. R heart strain
ABG – Low O2/Co2
CXR – Usually normal potentially with wedge infarcts
V/Q scan – indeterminate in 50-70%
CT pulmonary angiogram - definitive

18

Pulmonary Embolism: DVT and PE sequelae

PE →
• Pulmonary Hypertension → Chronic PE
• Death
Deep Vein insufficiency
• Post-thrombotic syndrome
• Venous ulcers

19

Pulmonary Embolism: Management of VTE

Fast acting anticoagulation minimum 3 moths (LMW Heparin or rivaroxaban)
• PE with haemodynamic effect may need thrombolysis or thrombectomy
• DVT graded compression stocking for PTS (minimum 6 months post DVT)
Long term anticoagulation?
Depends on individualised risk vs. benefit

20

Pulmonary Embolism: Who is at risk of VTE

Genetic risk factors
Acquired risk factors:
• Immobility
• Trauma and surgery
• Pregnancy and peurperium (post natal care)
• Oestrogen therapy (e.g. COCP, HRT)
• Inflammatory disorder (e.g. IBD)
• Myeloproliferative disorders (e.g. Essential Thrombocythaemia)
• Malignancy (e.g. Adenocarcinoma)
• Antiphospholipid syndrome

21

Factor V Leiden: Definition

Sequence change in Factor V prevents inactivation by Protein C
5-10% Caucasians

22

Factor V Leiden: Epi

5-10% Caucasians
Found in 20% of individuals with unexplained thrombosis
FVL – increased risk of VTE x 4
COCP – increased risk of VTE x4
COCP + FVL – increased risk of VTE x16

23

Anti-phospholipid syndrome: Clinical features


CLOTs:
C: Arterial or Venous thrombosis
L: Livedo reticularis
O: Obstetric complications - Recurrent miscarriage
T: Thrombocytopaenia

24

Anti-phospholipid syndrome: Caused by

Antiphospholipid antibodies – bind to membrane phopspholipid glycoprotein complexes

25

Anti-phospholipid syndrome: Primary or Secondary to

Connective tissue disease (SLE)
Lympjoproliferative disorders (e.g. Lymphoma, CLL)
Infection
Drug induced

26

Anti-phospholipid syndrome: Antiphospholipid antibodies

Anti-cardiolipin antibodies
Anti-beta2 glycoprotein antibodies
Lupus anticoagulants
• Prolonged aPTT in the test tube
• Is definitely not physiological anticoagulant – lab artefact

27

Antithrombotic drugs

Anti-platelet agents
Anti-coagulants

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Anti-platelet act to

Arterial: Inhibit arterial thrombosis (ACS, PVD, CVD)

29

Anti-coagulant drugs

Veins and low pressure vessels:
Inhibit coagulation pathway
Inhibit venous/low pressure thrombosis (DVT, PE, CVA in AF and mechanilca heart valves, CBP, dialysis)

30

UK Licensed anticoagulants

Inhibit production of thrombin:
• UF Heparin
• LMW heparin
• Warfarin
• Danaparoid
• Fondaparinux
• Bivalirudin
• Argatoban
• Apixiban
• Dabigatran
• Rivaroxaban

31

Heparin: Description

Paraentral antithrombotic
Naturally occurring glycosaminoglycan
Mixture of different wave lengths (UFH av. 50) (LMWH av. 15-20)

32

Heparin: MOA

Increases activity of natural anticoagulant Antithrombin
Inhibits active clotting factors esp. Factors IIa and Xa

33

UF Heparin Route

IV

34

UF Heparin bioavailability

Variable poor

35

UF Heparin Metabolism

Complex, renal

36

UF Heparin half life

1-2

37

UF Heparin adverse effects

Bleeding
(Heparin induced thrombocytopenia)

38

LMW Heparin route

SC

39

LMW Heparin bioavailability

Predictable, good

40

LMW Heparin metabolism

Predictable, renal

41

LMW Heparin half life

4-6

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LMW Heparin adverse effects

Bleeding

43

LMWH used in


1. Immediate management of VTE
2. Thromboprophylaxis
3. Acute coronary syndromes
4. Warfarin unsuitable esp pregnancy
5. Prophylaxis against venous thrombosis

44

UFH

6. 1. Extra-corporeal circuits
7. High risk ‘bridging’ for surgery

45

UHF Heparin: Absorption

Bolus Injection then IV infusion e.g. 5000 IU loading then 30,000 IU/24 hrs

46

UHF Heparin: Measure of heparin

• aPTT is best measure of heparin in ‘therapeutic’ activity range
• Expressed as aPTT ratio (patient aPTT/ normal aPTT)

47

UHF Heparin: Target aPTT range

1.5-2.5

48

UHF Heparin: Monitor

PLT count

49

LMW Heparin: Absorption

Four preparations – enoxaparin (Clexane)

50

LMW Heparin: Dosing

‘Prophylaxis’ 40 mg sc od
‘Treatment’ 1.5 mg/kg od or 1mg/kg bd

51

LMW Heparin:Monitoring

Not routine, won’t increased aPPt or PT at therapeutic levels
Anti-Xa test

52

LMW Heparin: Over-anticoagulation with heparin: mild or moderate bleeding

Stop Heparin

53

LMW Heparin: Over-anticoagulation with heparin: Severe

Stop Heparin
Protamine iv 1mg.100 IU heparin in lst hour max 40 mg)
Expect repeat treatment

54

Warfarin: Action

Oral anticoagulant
A coumarin derivative

55

Warfarin: MOA

Inhibits recycling of vit K
Vit K is needed for synthesis of clotting factors II, VII, IX and X

56

Warfarin: When do we use warfarin

Long term management of VTE
Stroke prevention in atrial fibrillation
Sometimes, prevention of arterial thrombosis (plus antiplatelet agent)

57

Warfarin: Absorption

Near 100% bio-availability

58

Warfarin: Half life

36 hours

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Warfarin:Metabolism

Liver

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Warfarin: Causes

Increased PT and increased aPTT

61

Warfarin: Monitoring

Longterm monitoring using INR (patient PT/ control PT)

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Warfarin:Typical dose

2-8mg od

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Warfarin: Interactions

Cranberry and grapefruit juice

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Warfarin:INR >5 and/or mild bleeding

STOP Warfarin

65

Warfarin INR >8 and/or serious bleeding

STOP warfarin
Vitamin K 1-3 mg poor iv
Consider Vitamin K factor concentrate (eg Octaplex) plus Vit K1

66

Rivaroxaban: MOA

Oral anticoagulant
Direct inhibitor of factor Xa

67

Rivaroxaban: When do we use rivaroxaban

• VTE after knee/hip replacement (10 md od)
• Stroke prevention in non-valvular AF (20mg od)
• Acute treatment of DVT (15 mg bd)
• Long-term prevention of DVT and PE (20 mg od)

68

Rivaroxaban: Peak plasma hours

• 3 hours

69

Rivaroxaban:Half life

• 8 hours

70

Rivaroxaban: Metabolism/excretion

• 75% liver metabolised/25% renal excreted

71

Rivaroxaban: Interactions

Some drug interaction and unsuitable in renal impairment.

72

Rivaroxaban: Monitoring

None

73

Rivaroxaban: May cause

• Increased PT and increased aPTT but doesn’t reflect anticoagulant effect.
• Anti-Xa test

74

Rivaroxaban: Accidental overdose or mild bleeding

• STOP rivaroxaban

75

Rivaroxaban: Serious bleeding

• STOP rivaroxaban
• General measures
• Specialist agents eg APCC

76

Rivaroxaban:Safety of anticoagulation

Anticoagulant bleeding leads iatrogenic mortality
High bleeding risk:
• Renal impairment (heparins and RIV)
• Previous bleeding edp. CNS or GI
• Other coagulopathy eg anti-platelet drugs
• Age >75 years, frequent falls, bw <50 kg

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