Hypercoagulable states - BB Flashcards

1
Q

Virchow’s triad

A

Endothelial damage

Stasis of blood

Hypercoagulability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Natural anticoagulants made by endothelial cells

A

NO, prostaglandins, antithrombin, tPA, APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Reasons why malignancy may cause hypercoagulable state:

A
  1. Some tumours produce pro-coagulants (TF)
    1b. Adenocarcinomas - some data that mucin is thrombogenic
  2. Normal cells may produce pro-coagulants (in reaction to the presence or growth of the tumour)
  3. Decreased activity, surgery and bed rest of the patient
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why does pregnancy cause hypercoagulable state?

A
  • Possible evolved to protect against blood loss at delivery
  • Many clotting factor level changes
  • – increased fibrinogen
  • – decreased protein S
  • Foetus obstructs venous return - pooling of blood in lower extremities (stasis)
  • – Hence DVT common
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why does oral contraceptive cause hypercoagulable state?

A

Oestrogen increases production of coagulation factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Elevated presence of which amino acid causes hypercoagulable state

A

Homocysteine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why does elevated homocysteine cause a hypercoagulable state?

A

High levels may cause - A+V clots

  • Endothelial injury
  • Activation of some clotting factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What causes elevated homocysteine?

A

Deficiencies:

  • Folate
  • B12
  • B6

Homocystinuria - (cystathionine beta synthase deficiency)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why does nephrotic syndrome cause a hypercoagulable state?

A

Multiple mechanisms - main one is:

- loss of anti-clotting factors in the urine (antithrombin III)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Inherited hypercoagulable states (thrombophilia)

x4

A
  1. Factor V Leiden Mutation
  2. Prothrombin gene mutation
  3. Antithrombin deficiency
  4. Protein C/S deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Factor V Leiden Mutation - how it works

A

Abnormal factor V - not inactivated by APC:S

Means that factor V remains active for longer -=> causing hypercoagulability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Genetics of factor V leiden mutation

A

Point mutation in factor V gene

Results in:

  • single amino acid substituion
  • guanine to adenine change

Occurs at position 506 on factor V molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Prothrombin gene mutation genetics:

A

Prothrombin 20210 gene

  • guanine to adenine change in prothrombin gene
  • occurs at position 20210

Heterozygous carriers have 30% increase in prothrombin
Homozygous carriers have even higher

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

ATIII deficiency (antithrombin) 2 types:

A
  1. Inherited due to gene mutations (number of different mutations can cause)
  2. Acquired deficiency
    a- Liver disease (impaired production)
    b- Nephrotic syndrome (Protein losses including ATIII)
    c- DIC (consumption of both anti-/coagulant factors)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Typical presentation of antithrombin III deficiency

A

Heparin resistance

  • escalating dose with little to no change in PTT
  • Because no ATIII for heparin to work on
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Protein C or S deficiency presentation:

A

Associated with warfarin skin necrosis (thrombosis of skin tissue)
—- Large dark purple skin lesions

  • Protein C has short half life and so is first vitamin K factor to fall when warfarin is administered
17
Q

Protein C or S deficiency: (why does it occur)

A

Because of loss of inhibitory actions of APC on Va and VIIIa

Excessive activation of clotting factors

18
Q

Antiphospholipid syndrome causes

A

Antiphospholipid antibodies

Occurs either in association with lupus or primary disease

19
Q

Clinical concequences of antiphospholipid syndrome (X3)

A
  1. Increased risk of V/A thrombosis
    - – Most commonly DVT but also stroke
    - – Recurrent foetal losses
  2. Increased PTT
  3. False positive for syphilis (RPR/VDRL)
    - - if this antibody is present
20
Q

3 Types of antiphospholipid antibodies

A
  1. Anti-cardiolipin
    • – False positive for syphilis (because it also produces these antibodies)

2 ‘Lupus anticoagulant’
— Interferes with PTT test (intrinsic)

  1. Anti-beta2 glycoprotein
21
Q

Antibody detection in antiphospholipid syndrome:

A

For anti-cardiolipin + anti-beta” glycoprotein:
— ELISA (enzyme linked immunosorbent assay testing)

For ‘Lupus anticoagulant’:
— Usually detected indirectly through coagulation assays (PTT)

22
Q

‘Lupus anticoagulant’ testing

A
  1. PTT mixing test - to show the presence of an inhibitor

– Clotting factor deficiencies (e.g. hemophilia) will correct to normal in a mixing PTT test
(only 50% of patients with lupus anticoagulant have a raised PTT)

(*if still suspicious despite no raised PTT move on)

  1. Dilute Russell Viper Venom Time
  2. Kaolin clotting time

(in remaining tests time to clot will be prolonged if LA is present)
—- Time will not correct with mixing study

23
Q

Criteria for antiphospholipid syndrome:

A

Many patients have antiphospholipid antibodies but no syndrome

To have syndrome you must have 1 lab and 1 clinicla criteria

Lab criteria (2 positive results 12 weeks apart)

  • Lupus anticoagulant
  • anti-cardiolipin
  • anti-beta2-glycoprotein

Clinical criteria:

  • A/V thrombosis
  • foetal death after 10 weeks of normal foetus
  • > =3 consecutive foetal losses before 10 weeks
24
Q

Workup that can be done in patients who are hypercoagulable:

A
Antithrombin levels
Protein C and S levels
Factor V Leiden gene mutation
Prothrombin gene mutation 
Antiphospholipid antibodies 
Cancer screening (age appropriate)