Tests of Coagulation

Question 1

What are the factors involved in primary hemostasis? What areas are at risk?

Answer 1

Platelets, von Willebrand’s, fibrinogen
areas at risk of damage: skin, mucosa, endothelium
Petechiae and ecchymoses associated with primary

Question 2

What are the factors involved in secondary hemostasis? What areas are at risk?

Answer 2

clotting factors of the cascade

Areas at risk of damage if those proteins not present: joints, deep tissue

Question 3

What is bleeding time test used for?

Answer 3

A Screening test for the primary platelet plug.

• In vivo measure of time to clot for skin incision
• Indirect assessment of platelet number & effective interaction with subendothelial vWf (IbIX), other platelets (IIbIIIa, fibrinogen)
• Normal adult <9 mins (simulate)
• Highly performer-dependent
• Not a reliable predictor of procedure-associated hemorrhage in patients without a bleeding hx
• Normal bleeding times do not reliably rule out the possibility of operative hemorrhage
• Not reliably correlated with exposure to aspirin or NSAIDS

Question 4

What is the PFA-100 test used for?

Answer 4

A screening test for the primary platelet plug

• Anticoagulated whole blood is passed through a narrow tube with a membrane coated with collagen + ADP or EPI
• Closure Time (CT) = time it takes to occlude (clot) the aperture
• Superior to bleeding time as a screen for platelet dysfunction, mod-severe vWD, Aspirin effect

Question 5

What are the specific tests of platelet function?

Answer 5

1. Platelet aggregometry: a series of tests performed on whole blood or platelet-rich plasma, using several agonists (platelet activators). Measure of platelet clumping is recorded. agonists include thrombin, ADP, etc.
2. von Willebrand factor antigen- quantitative measure of vWf:Ag
3. Ristocetin Cofactor Assay- often used with #2, tests the ability of vWF to bind platelet GP1b. A functional tests of vWF, usually parallels vWF: Ag, if it doesn’t, then there’s something wrong

Question 6

What does the activated Partial Thromboplastin Time test? (aPTT) How does the test work?

Answer 6

The intrinsic pathway, also affected by deficiencies in common pathway
-Citrated plasma (which binds calcium=anticoag) is combined with phospholipid and contact activator.
-Calcium is added and the time to clot is measured
-the test is most sensitive for deficiencies in VIII, IX, XI, XII when their concentration is <30%
-mild but significant deficiencies might be missed
-correlation between degree of prolongation and factor level better for VIII than others
Normal range: 23-33 s

Question 7

What does the Prothrombin time test? How does it work?

Answer 7

The extrinsic pathway
tests for deficiency in factor VII, also affected by deficiencies in common pathway
-brain tissue (thromboplastin)+citrated plasma
-add calcium and measure time to clot
-PT begins to prolong with 50-60% factor deficiency

Question 8

What are the factors in the common pathway?

Answer 8

X, V, II, I
which affect both PT and aPTT
I = fibrin
II =prothrombin

Question 9

What is the order of clotting factors that get activated in the intrinsic pathway?

Answer 9

XII, XI, IX, VIII

12, 11, 9, 8

Question 10

When can you get spurious prolongation of aPTT?

Answer 10

1. elevated HCT (elevated citrate: plasma)
2. heparin in tube (anticoag)
3. clotted sample (pulls factors out of sample)

Question 11

How should you workup a prolonged aPTT?

Answer 11

50: 50 mixing study where 50% patient’s plasma mixed with 50% control plasma
- deficiency: only 30-40% normal factors needed for normal aPTT, so if deficiency, it should be corrected
- –> follow up with assay for factors XII, XI, IX, VIII
- inhibitor: if doesn’t correct, an inhibitor is present and inhibits the same factor in control plasma and in patient
- —>follow up with test for lupus anticoagulant, anticardiolipin antibodies
- if negative, test for specific factor inhibitors

Question 12

What are inherited factor deficiencies that are not associated with bleeding?

Answer 12

XII, PK, HMWK

Question 13

How would you workup a prolonged PT?

Answer 13

50: 50 mixing study
- corrects: deficiency
- prolonged still: inhibitor

Question 14

What does the thrombin time test for? How does the test work?

Answer 14

Thrombin+citrated plasma, measure thrombin clotting time

• measures rate of conversion of fibrinogen to fibrin
• depends on: quality and quantity of fibrinogen (need min of 75-100mg/dL of fibrinogen for normal time)

Question 15

What are conditions associated with prolonged thrombin time?

Answer 15

• Congenital afibrinogenemia, dysfibrinogenemia
• Heparin (confirm with Reptilase test which still clots fibrinogen in presence of heparin)
• Excess Fibrinogen degradation products (FDPs – as in DIC)
• Paraproteinemia (inhibits polymerization)
• Renal failure

Question 16

What are tests used to test for defects in fibrinolysis?

Answer 16

1. Euglobulin Lysis time
2. dilute whole blood clot lysis time
   - Screening for accelerated fibrinolysis
   - Measures the time to clot breakdown in a sample of plasma (ELT) or whole blood (DWBCLT)
   - Shortened in: advanced cirrhosis, alpha2-antiplasmin deficiency, plasminogen activator inhibitor-1 deficiency, systemic fibrinolysis
   - Occasionally prolonged in venous thrombosis and renal disease (increase PAI-1 levels)

Question 17

What are the screening tests for defects in primary hemostasis?

Answer 17

• Patient and family hx
• blood smear
• bleeding time
• PFA-100

Question 18

What are some conditions that prolong bleeding time?

Answer 18

-Inherited:
Glanzmann’s Thrombasthenia (IIbIIIa)
Bernard Soulier (IbIX)
Von Willebrand’s Disease
\+/- Platelet granule defects
-Acquired:
Uremia
Paraproteinemia
Severe anemia
Liver disease
Drugs: Aspirin, NSAIDS, other