Lab Investigation of Coagulation Disorders...including Reflex Tests Flashcards

1
Q

Mixing studies

- Principle of the test

A
  • If PT/APTT are normal, stop!
  • But if either or both are prolonged and can’t be explained by disease or drugs, then mixing studies are ordered
  • Determines if results are due to either factor deficiency or inhibitor to coagulation
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2
Q

Mixing studies

- Testing procedure

A
  1. Determine which part of the cascade is affected…possible factors
  2. Rule out heparin contamination
  3. Mix patient plasma w/ pooled normal plasma (PNP)
  4. Proceed w/ confirmatory testing
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3
Q

Mixing studies

- Interpretation of results

A

After ruling out heparin contamination, and mixing w/ PNP:

  • Correction: suspect a factor deficiency
  • No correction: suspect an inhibitor
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4
Q

How do you determine the presence of heparin?

A

Add protamine sulfate or hepzyme to the patient’s plasma and rerun abnormal test:

  • If tests are normal: stop, the increase was due to heparin
  • If tests are still prolonged: proceed
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5
Q

How do you determine the presence of a deficient factors?

A

Make a mixture of 50% patient: 50% PNP and run the mixtures

  • If mixture immediately corrects the abnormal results to w/in 10% of normal, suspect a factor deficiency
  • If mixture does not correct, suspect inhibitor (circulating anticoagulant)
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6
Q

How do you determine the presence of a circulating anticoagulant?

A

If 50:50 mixture does not correct, suspect an inhibitor (circulating anticoagulant)

  • Specific factor inhibitors or
  • LLAs (lupus-like anticoagulants)
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7
Q

Factor Assay

- Principle

A

The degree to which the patient plasma corrects (or fails to correct) a specific factor deficient substrate…is compared to a reference curve/standard curve

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8
Q

Functional Fibrinogen Assay

- Principle

A

(Modification of the TCT)
- When “excess” thrombin is added to “dilute” patient’s plasma, the time required for a clot to form is inversely proportional to the fibrinogen concentration (less fibrinogen would be slow to clot/more fibrinogen would be quick to clot)

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9
Q

Two classifications of circulating anticoagulants

A
  • Specific factor inhibitors

- LLAs (lupus-like anticoagulants)…aka non-specific inhibitors or antiphospholipid Abs

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10
Q

Specific factor inhibitors

- Definition

A

Ab that destroys a specific factor in progressive, time-consuming fashion

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11
Q

Specific factor inhibitors

- Occurrence

A
  • Secondary to factor infusions used in Hemophilia A and B treatment (approximately 30%)
  • Secondary to txn
  • Spontaneously
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12
Q

Specific factor inhibitors

- Lab results (screening and mixing studies)

A
Screening:
- Normal PT
- Prolonged APTT
Mixing studies:
- PNP does NOT correct (times will get progressively longer w/ extended incubation)
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13
Q

Specific factor inhibitors

- Confirmatory test(s)

A

Bethesda titer (to quantify inhibitor)

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14
Q

LLAs

- Definition

A

Antiphospholipid Abs, aka LLAs, are blood proteins that appear following a viral infection or during the course of a chronic inflammatory condition like arthritis (e.g., lupus) or cancer

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15
Q

LLAs

- Occurrence

A
  • Detectable in 1-2% of people, but usually disappear w/in 6 weeks
  • Those whose LLAs do not disappear present w/ a 30% risk of thrombosis
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16
Q

LLAs

- Lab results (screening and mixing studies)

A
Screening:
- Prolonged PT
- Prolonged APTT
Mixing studies
- PNP does NOT correct
- Times do NOT get progressively longer w/ extended incubation
17
Q

LLAs

- Confirmatory tests

A
  • Platelet neutralization test (PNT)

- Dilute Russell’s Viper Venom Test (dRVVT)

18
Q

LLAs

  • In vitro effects
  • In vivo effects
A

In vitro
- Inhibit the assembly of prothrombinase complex (Xa, Va, Ca2+, PL)
In vivo
- No effect

19
Q

Method to screen for a suspected deficiency of Fletcher factor

A
  • Rerun APTT and extend incubation to 15 minutes (instead of the usual 3-5 minutes)
  • If abnormal time “partially corrects” think of PK deficiency
  • WHY: allows time for “feedback mechanism” to help correct abnormal clotting time
20
Q

Typical results for deficiency of Fletcher factor

A

If abnormal time “partially corrects” think of PK deficiency

- WHY: allows time for “feedback mechanism” to help correct abnormal clotting time

21
Q

What test is used to confirm a Factor XIII deficiency?

A

Urea Solubility Test

22
Q

Expected test results for a vascular disorder

  • Platelet count
  • PT
  • APTT
  • BT
A
  • Platelet count: Normal
  • PT: Normal
  • APTT: Normal
  • BT: Abnormal
23
Q

Expected test results for a fibrinolytic disorder (acquired):

  • Platelet count
  • PT
  • APTT
  • BT
A
  • Platelet count: Abnormal
  • PT: Abnormal
  • APTT: Abnormal
  • BT: Abnormal
24
Q

Expected test results for a quantitative platelet disorder:

  • Platelet Count
  • PT
  • APTT
  • BT
A
  • Platelet Count: Abnormal
  • PT: Normal
  • APTT: Normal
  • BT: Abnormal
25
Q

Expected test results for a qualitative platelet disorder :

  • Platelet Count
  • PT
  • APTT
  • BT
A
  • Platelet Count: Normal
  • PT: Normal
  • APTT: Normal
  • BT: Abnormal
26
Q

Expected test results for a Factor disorder:

  • Platelet Count
  • PT
  • APTT
  • BT
A
  • Platelet Count: Normal
  • PT: Abnormal (dependent on factor def)
  • APTT: Abnormal (dependent on factor def)
  • BT: Normal
27
Q

What are some possible causes of the following test results:

  • APTT: abnormal
  • PT: abnormal
  • Thrombin time: normal
A
  • Vitamin K deficient
  • Liver disease
  • Inhibitor present
  • Factor deficiency in common pathway (X, V, III)
28
Q

What are some possible causes of the following test results:

  • APTT: abnormal
  • PT: normal
A
  • Factor deficiency in intrinsic pathway (XIII, Xi, IX, VIII, Fletcher, Fitzgerald)
  • Lupus anticoagulant
  • Specific factor inhibitor
29
Q

What are some possible causes of the following test results:

  • APTT: normal
  • PT: abnormal
A
  • Factor deficiency in the extrinsic pathway (VII)

- Specific factor inhibitor

30
Q

What are some possible causes of the following test results:

  • APTT: abnormal
  • PT: abnormal
  • Thrombin time: abnormal
A
  • Factor I deficiency
  • Severe liver disease
  • DIC
  • Potent inhibitor
  • Hypofibrinogenemia or dysfibrinogenemia
31
Q

What are some possible causes of the following test results:

  • APTT: normal
  • PT: normal
  • Thrombin time: normal
A
  • Factor XII deficiency
  • Specific factor inhibitor
  • Normal patient or lab error