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MBCHB3: Blood, Immunity and Infection > Lecture 13: Coagulation disorders > Flashcards

Lecture 13: Coagulation disorders Flashcards

1
Q

What are the laboratory tests for clotting?

A

APTT
PR (Prothrombin ratio)
TCT

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2
Q

What pathways do the various lab tests assess?

A

APTT = Intrinsic pathway

Prothrombin ratio = Extrinsic pathway

Thrombin clotting time = Thrombin / platelet function

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3
Q

What factors does the APTT assess?

A

All factors except factor 7.

Therefore prolonged APTT could be any factor deficiency except 7.

Xii, Xi, IX, Viii are APTT only.

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4
Q

What is APTT and how is it done?

A

Activated partial thromboplastin time

  • Venous blood sample collected into citrate (removes Ca and prevents clotting, chelate)
  • Spin down, plasma collected
  • Phospholipid + Activator + Ca added
  • Length of time to form clot is informative.
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5
Q

What are the contact factors for APTT?

A

Contact factor

  • Kaolin
  • Silica
  • Ellagic acid

Contact factor + Phospholipid + Ca

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6
Q

What is prothrombin time measuring and how is it done?

A

It is measuring the time for prothrombin to form, it reflects factors 5, 7, 10

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7
Q

How is prothrombin time expressed?

A
  • Converted to prothrombin ratio
  • Prothrombin time (patient) / prothrombin time (normal plasma)
  • Normally is around 1
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8
Q

What does prolonged PR and APTT indicate?

A

Common factor deficiency

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9
Q

What is thrombin clotting time? what can it be used to measure?

A

Measures fibrinogen

  • Can be used to measure impact of inhibitors such as heparin and dibigotran
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10
Q

Whats normal APTT?

A

25-37 seconds

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11
Q

What can be done to follow up on a prolonged APTT and how does it work?

A

Mixing studies: i.e is a factor deficiency or inhibitor present

1:1 mixing with normal plasma + incubation
= Sample corrects to normal and remains normal indicating a factor deficiency in patient.

Sample does not fully correct then an inhibitor is present

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12
Q

Describe the physiological inhibitors impact on APTT:

A

Antithrombin, protein C+S are natural inhibitors and DO NOT affect APTT

Inhibitors that affect APTT are different

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13
Q

What inhibitors prolong the APTT 1+1?

A

Lupus anticoagulant
Factor inhibitors i.e autoimmune antibodies
Heparin
Debigatran

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14
Q

How does lupus anticoagulant prolong APTT 1+1? whats its impact on bleeding?

A
  • Might be part of antiphospholipid syndrome
  • Can present transiently in patients whom are unwell
  • Antibodies in plasma interfere with APTT assay

DOES NOT CAUSE BLEEDING

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15
Q

Write some notes on factor autoantibodies and they impact on bleeding?

A
  • Usually anti-factor 8
  • Can be life threatening
  • Associated with bleeding including bruising

RARE but should be considered in bleeding patient

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16
Q

How does heparin interfere with ATPP 1+1 and its impacts on clotting:

A
  • Heparin causes prolonged 1+1
  • Confirmed by the addition of protamine (Corrects it)
  • Heparin upregulates antithrombin (GAG chains)
  • Biological GAGs dont affect APTT B/c heparin infusion is much larger amount
  • Thrombin clotting time also very prolonged. (but again corrected with protamine)
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17
Q

What is heparin commonly used for and how can it contaminate samples?

A
  • Commonly used to lock central lines…

- Contamination common if tube collected this way

18
Q

How does dabigatran affect APTT?

A
  • Prolongs APTT 1+1 and DOES NOT correct with protamine
  • Direct inhibitor of thrombin
  • Thrombin clotting time also very prolonged. (DOES NOT correct with protamine)
19
Q

Interpret: APTT prolonged, PT normal:

A

Deficiencies of factor(s): 8,9,11,12

20
Q

Interpret: PT prolonged, APTT normal:

A

Deficiency of factor 7 (extrinsic)

Occasionally mild deficiencies of 2,5,10 or 1

21
Q

Interpret: Both PT and APTT prolonged:

A
  • Deficiency of factors 2,5,10 or 1 (common)

- Multiple factor deficiency

22
Q

What does prolonged TCT indicate?

A
  • Deficiency of fibrinogen

- Thrombin inhibitor (i.e dabigatran or heparin)

23
Q

What are some other ways of assessing clotting?

A
  • Single factor assays
  • Whole blood clotting tests
  • Primary heamostasis: platelet function testing
  • D-dimers
24
Q

What commonly leads to multiple factor deficiencies?

A
  • Warfarin or Vit K deficient (Factors 2, 7, 9, 10)
  • Massive blood loss i.e loss of coag factors + fluids dilution
  • DIC (factors, platelets and fibrinogen used up)
  • Liver disease: Lack of factors and inhib production (except factor 8)
25
Q

What can cause a prolonged PT?

A

Extrinsic pathway (APTT normally prolonged also)

  • Warfarin or Vit K deficient (2,7,9,10)
  • Liver disease
  • Low factor 7 (APTT normal)
26
Q

How is a prolonged PT monitored?

A

Monitor with International Normalized Ratio

27
Q

How does warfarin function?

A

Inhibits recycling of Vit K

  • Doses are adjusted based on the INR
  • Used in atrial fibrilation, venous thromboembolism etc
28
Q

How is warfarin reversed?

A

Vit K (or plasma products replacing clotting factors)

29
Q

Describe the symptoms of severe heamophilia:

A

Spontaneous joint bleeds

  • Chronic arthropathy
  • Joint destruction
  • Arthritis

Soft tissue bleeds

  • Tissue damage
  • Nerve damage
  • Deformity
30
Q

Whats happening in heamophilia A?

A
  • Factor 8 deficiency
  • X linked
  • Mild to severe bleeding
31
Q

Whats happening in heamophilia B?

A
  • Deficient in factor 9
  • X linked recessive
  • Clinical features identical to A
32
Q

Whats the most common COD for heamophilia?

A

Intracranial bleed was the commenest cOD

33
Q

Whats the treatment for heamophilia?

A

Replace the missing factor, normal outcomes except when inhibitors develop

34
Q

How is heamophilia tested and diagnosed?`

A
  • Prolonged APTT, normal PR
  • Single factor assays; low factor 8 or 9
  • Genetic analysis
35
Q

What else can cause low factor 8?

A

Von willibrand disease

36
Q

What does VWF do?

A
  • Tethers platelets to vessel walls

- Serves as carrier for factor 8, stabilizing it and preventing degredation

37
Q

What is the most common inherited bleeding disorder?

A

Von willibrand disease

- Autosomal dominant

38
Q

How is von willibrands disease tested?

A
  • Abnormal platelet screen
  • Marginally prolonged APTT (not all)
  • Low factor 8
  • Low level and function of VWF
39
Q

What are the symptoms of VWF?

A

Mucosal bleeding

  • Epistaxis
  • Gum bleeds
  • GI loss

Bruising
Menorrhagia
Post-partum or perioperative bleeding

Autosomal family history

40
Q

What can cause DIC?

A

Sepsis-many bacteria
Malignancy
Organ damage i.e pancreatitis
Trauma

MBCHB3: Blood, Immunity and Infection (41 decks)

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