Haem: Thrombosis - aetiology and management Flashcards

1
Q

What is the triad of symptoms in thrombophlebitic syndrome?

A

Recurrent pain

Swelling

Ulcers

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2
Q

What catalyses the conversion of fibrinogen to fibrin?

A

Thrombin

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3
Q

Which anticoagulant molecules are expressed on the blood vessel wall?

A

Thrombomodulin

Endothelial protein C receptor

Tissue factor pathway inhibitor

Heparans

NOTE: it does not normally produce tissue factor

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4
Q

What antiplatelet factors are secreted by the vessel wall?

A

prostacyclin

NO

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5
Q

What is expressed in the subendothelial wall which triggers coagulation?

A

TF, collagen

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6
Q

Recall 5 effects of inflammation on the blood vessel wall

A
  1. Anticoagulant molecules are downregulated
  2. TF expressed
  3. Prostacyclin decreased
  4. Adhesion molecules upregulated
  5. VWF released (leading to neutrophil capture, and formation of NETs)
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7
Q

How do neutrophils contribute to immunothrombosis?

A

Neutrophils release DNA via NETosis, which is procoagulant

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8
Q

Give 4 ways in which blood stasis promotes thrombosis

A
  1. Accumulation of activated factors
  2. Promotes platelet adhesion
  3. Promotes leukocyte adhesion (NET) and transmigration
  4. Hypoxia produces inflammatory effect on endothelium (adhesion, vWF release)
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9
Q

Causes of stasis

A

immobility: surgery, paraparesis, travel
compression: tumour, pregnancy
viscosity: polycythaemia, paraprotein
congenital: vascular abnormalities

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10
Q

What is the broad mechanism of action of heparins?

A

Potentiate antithrombin

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11
Q

Give some examples of immediate and delayed anticoagulants

A

immediate: heparin (unfract or LMWH), direct acting anti-Xa and anti-IIa

delayed: vit K antagonists (warfarin)

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12
Q

Give an example of an LMWH

A

Enoxaparin/ Tinzaparin

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13
Q

How is unfractionated heparin monitored?

What about LMWH?

A

Unfractionated heparin: it has variable pharmacokinetics and a variable dose-response

Must be monitored with APTT or anti-Xa levels

IV

LMWH: reliable pharmacokinetics so monitoring usually not required

Monitor anti-Xa levels if there is renal failure, extreme weight or extreme risk

sub-cut

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14
Q

What are the disadvantages of heparin?

A

Administered by injection

Risk of osteoporosis

Variable renal dependence

Risk of heparin-induced thrombocytopaenia

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15
Q

How does warfarin affect vit K?

A

Warfarin inhibits vitamin K epoxide reductase

Prevents recycling of Vit K

indirectly acting

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16
Q

Which procoagulant factors fall as a result of warfarin medication?

A

II, VII, IX and X

*Also impairs Protein C and Protein S (which are natural anticoagulant molecules)*

17
Q

How can the action of warfarin be reversed?

A

Administering vitamin K – takes 12 hours

Giving factors 2, 7, 9 and 10 – immediate

18
Q

How is warfarin monitored?

A

Pro-thrombin time/INR

19
Q

What are the problems with warfarin?

A

Teratogenic so cannot give during pregnancy

Initial hypercoagulable state due to inhibition of protein C and protein S - that’s why heparin is co-administered until INR stabilises

Interactions with other drugs: metabolised by cytochrome

Variable absorption

Dietary vit K

20
Q

List some properties of DOACs

A

Oral administration

Immediate action (peak = 3-4 hours)

Useful in long-term

Short half-life

No monitoring needed

NOTE: contra-indicated in valvular AF

21
Q

Which DOAC inhibits factor IIa?

Which DOACs inhibit factor Xa?

A

IIa: Dabigatran

Xa: Rivaroxiban Apixaban Edoxaban

22
Q

Which surgeries carry the highest risk of thrombosis?

A

Orthopaedic

23
Q

Which of these factors are associated with a higher risk of recurrence of DVT?

Male sex

Female sex

Proximal thrombosis

Distal thrombosis

Post surgery

Idiopathic

A

Male sex

Proximal thrombosis

Idiopathic

24
Q

Risk factors for thrombosis

A

Cancer

Surgery

Obesity

Elderly

Immobility

*Antithrombin deficiency confers the highest risk*

25
Q

What should all patients > 60 years old with idiopathic thromboembolic disease be offered?

A

CT scan to check for an underlying cause

26
Q

Outline the treatment of DVT/PE.

A

Start LMWH (e.g. tinzaparin 175 u/kg) + warfarin

Stop LMWH when INR > 2 for 2 days

ALTERNATIVE: start a doac

These should be continued for:

  • Known cause: 3 months
  • Unknown cause or cancer VTE: 3-6 months
  • Thrombophilic/recurrent: lifelong
27
Q

How do you prevent venous thrombosis recurrence?

A

After a surgical precipitant: no long-term anticoagulation needed

After a minor precipitant: 3 months anticoagulation usually adequate

If idiopathic cause: long-term anticoagulation (10-20% recurrence within 2 years)

28
Q

Mortality of VTE

A

5% and 20% recur in first 2 years

29
Q

Consequences of VTE

A
  • death
  • recurrence
  • thrombophlebitic syndrome
  • pulmonary hypertension
30
Q

VIRCHOWS triad

A

blood

vessel wall

blood flow

31
Q

Blood factors affecting VTE

A

haematocrit and protein levels

platelet count high

excess of coagulation factors

32
Q

Thromboprophylaxis methods

A

LMWH: low dose i.e. tinzaparin 4500units/ enoxaparin 40mgOD

TED stockings for surgery/ heparin CI

intermittent pneumatic compression

sometimes DOAC +/ aspirin

33
Q

Where on the leg does distal thrombosis occur

A

below popliteal bone, low risk recurrence but proximal high risk