Lab Investigation of Coagulation Disorders...including Reflex Tests Flashcards
Mixing studies
- Principle of the test
- 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
Mixing studies
- Testing procedure
- Determine which part of the cascade is affected…possible factors
- Rule out heparin contamination
- Mix patient plasma w/ pooled normal plasma (PNP)
- Proceed w/ confirmatory testing
Mixing studies
- Interpretation of results
After ruling out heparin contamination, and mixing w/ PNP:
- Correction: suspect a factor deficiency
- No correction: suspect an inhibitor
How do you determine the presence of heparin?
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
How do you determine the presence of a deficient factors?
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)
How do you determine the presence of a circulating anticoagulant?
If 50:50 mixture does not correct, suspect an inhibitor (circulating anticoagulant)
- Specific factor inhibitors or
- LLAs (lupus-like anticoagulants)
Factor Assay
- Principle
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
Functional Fibrinogen Assay
- Principle
(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)
Two classifications of circulating anticoagulants
- Specific factor inhibitors
- LLAs (lupus-like anticoagulants)…aka non-specific inhibitors or antiphospholipid Abs
Specific factor inhibitors
- Definition
Ab that destroys a specific factor in progressive, time-consuming fashion
Specific factor inhibitors
- Occurrence
- Secondary to factor infusions used in Hemophilia A and B treatment (approximately 30%)
- Secondary to txn
- Spontaneously
Specific factor inhibitors
- Lab results (screening and mixing studies)
Screening: - Normal PT - Prolonged APTT Mixing studies: - PNP does NOT correct (times will get progressively longer w/ extended incubation)
Specific factor inhibitors
- Confirmatory test(s)
Bethesda titer (to quantify inhibitor)
LLAs
- Definition
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
LLAs
- Occurrence
- 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