Bleeding Disorders Flashcards

1
Q

List the 4 main types of acquired bleeding disorder.

List the 4 main types of inherited bleeding disorders.

A
ACQUIRED:
Disseminated intravascular coagulation (DIC)
Drug effects (e.g. warfarin, DOACs)
Coagulopathy in liver disease
Lupus anticoagulant
INHERITED:
Clotting factor deficiencies (e.g. haemophilia A/B)
Von Willebrand factor deficiency
Platelet disorders
Thrombophilia
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2
Q

What are the 3 main features of disseminated intravascular coagulation (DIC)?

A

Microthrombi, due to inappropriate activation of coagulation cascade

Fragmentation anaemia, due to RBC damage by microthrombi

Bleeding, due to exhaustion of coagulation cascade

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3
Q

Describe the pathophysiology of DIC. (3)

A
  1. Systemic activation of coagulation causes:

a. Intravascular fibrin deposition, causing:
- Thrombosis of small vessels
- Organ failure

b. Depletion of platelets and clotting factors, causing:
- Bleeding

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4
Q

List 5 possible causes of DIC.

A
Sepsis
Malignancy
Massive haemorrhage
Severe trauma
Pregnancy complications, e.g.
-Pre-eclampsia
-Placental abruption
-Amniotic fluid embolism
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5
Q

Which investigations would you do for DIC? (7)

A

Investigate underlying cause

Coagulation tests:

  • PT
  • APTT
  • TCT

Blood tests:

  • FBC
  • Blood film
  • D-dimers
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6
Q

How would you treat DIC? (7)

A
Treat underlying cuase
Fresh frozen plasma
Platelet transfusion
Heparin (if thrombotic phenotype)
Antithrombin concentrate
Protein C concentrate
Activated protein C
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7
Q

What is the most significant side effect of warfarin?

A

Bleeding complications

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8
Q

What could you do if your patient is on warfarin, and their INR is too high? (5)

A
  1. Stop warfarin
  2. Reduce warfarin dose
  3. Give vitamin K (oral/IV)
  4. Give vitamin K dependent coagulation factors (2, 7, 9, 10)
  5. Give prothrombin complex concentrates (e.g. beriplex, octaplex)
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9
Q

List the 4 vitamin K dependent clotting factors.

A

2, 7, 9, 10

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10
Q

What type of drug is dabigatran? Outline its effect on:

a) PT
b) APTT
c) TCT

Which other test could you do to check dabigatran levels?

A

Direct factor 2a (thrombin) inhibitor

PT - no change
APTT - affected if very high levels of dabigatran
TCT - affected by slight changes in dabigatran levels

Ecarin clot time (ECT) - add snake venom to patient’s plasma; time taken for it to clot

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11
Q

What type of drug is rivaroxaban? What is its effect on:

a) PT
b) APTT

What other test could you do to check rivaroxaban levels?

A

Direct factor 10a inhibitor

PT - sensitive, dose depend change
APTT - weak, non-linear effect

Anti-10a assay - but calibration curve is still being established

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12
Q

In liver disease, why might you also see coagulopathy? (3)

A

Decreased clotting factor synthesis in liver
Vitamin K deficiency (e.g. poor diet, obstructive jaundice)
Poor clearance of activated coagulation factors

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13
Q

Describe the features of coagulopathy in liver disease. (5)

A
DIC
Hypersplenism
Low WBC
Low platelets
Decreased thrombopoietin synthesis
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14
Q

What is lupus anticoagulant?

What is its effect on:

a) PT
b) APTT
c) APTT 50:50

What other test could you do to detect lupus anticoagulant?

A

Phospholipid dependent antibody - i.e. binds to phospholipids

PT - normal
APTT - prolonged
APTT 50:50 - only partial correction

DRVVT ratio (dilute Russell's viper venom time) - snake venom added to plasma
-Results: prolonged (BUT corrected by excess phospholipid)
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15
Q

What are the main clinical features of antiphospholipid syndrome? (3)

Which antiphospholipid antibodies might be present? (3)

A

FEATURES:
Antiphospholipid antibodies
Thrombosis
Recurrent miscarriage

ANTIPHOSPHOLIPID ANTIBODIES:
Lupus anticoagulant
Anti-cardiolipin antibodies
Beta 2 glycoprotein 1 antibodies

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16
Q

Describe the pathophysiology of antiphospholipid syndrome. (3)

A
  1. Antiphospholipid antibodies disrupt the Annexin V shield and expose phospholipids
  2. This causes continuous activation of the clotting cascade
  3. This leads to thrombosis
17
Q

What is haemophilia A caused by?

How is it inherited?

A

Factor 8 deficiency

X-linked recessive inheritence

18
Q

How would you classify haemophilia A>

HINT: there are 3 levels of severity.

A

Mild:

  • Factor 8: 6-40 iu/dL
  • Surgical bleeding

Moderate:

  • Factor 8: 2-5 iu/dL
  • Minor trauma bleeds

Severe:

  • Factor 8: <1 iu/dL
  • Spontaneous bleeds
19
Q

In haemophilia, what would the following coagulation tests look like?

a) PT
b) APTT

Why?

A

PT - normal
APTT - prolonged

BECAUSE:
Haemophilia A is a factor 8 deficiency
Factor 8 is in the intrinsic pathway
APTT measures the intrinsic pathway, BUT PT only measures the extrinsic pathway (therefore isn’t affected)

20
Q

How would you treat haemophilia A? (5)

A

Patient/doctor education
Desmopressin (DDVAP)

Replacement therapy, e.g.

  • Recombinant produced factor 8 concentrate
  • FFP
  • Plasma derived factor 8 concentrate
21
Q

What is haemophilia B caused by?

A

Factor 9 deficiency

22
Q

Describe the features of Von Willebrand factor deficiency. (4)

A

Mucosal type bleeding pattern
Decreased VWF levels
Decreased platelet aggregation
Decreased factor 8

23
Q

How would you classify VWF deficiency?

HINT: there are 3 categories, but one of them has 4 subcategories.

A

Type 1 - partial quantitative VWF deficiency

Type 2 - qualitative VWF defiency:

  • 2A: absence of HMW VWF multimers
  • 2B: increased affinity for platelet GPIb-V-IX
  • 2M: decreased platelet dependent function NOT caused by lack of HMW VWF multimers
  • 2N: increased affinity for platelet GPIb-V-IX

Type 3 - almost complete VWF deficiency

24
Q

List 5 possible causes of thrombophilia.

A

Anticoagulant deficiencies, e.g.

  • Antithrombin
  • Protein C
  • Protein S

Specific gene mutations, e.g.

  • Factor 5 Leiden mutation
  • Prothrombin gene mutation
25
Q

If a bleeding disorder presents with a mucosal bleeding pattern, what is this associated with?

A

Platelet disorders