Lab Investigation of Coagulation Disorders...including Screening Tests

Question 1

What is the workup of a patient for bleeding disorders according to patient history?

Answer 1

Looking for past bleeding episodes, past surgeries, family history, drug history
- Has the bleeding been out of proportion to the challenge/injury???

Question 2

What is the work-up of a patient for bleeding disorder according to physical examination?

Answer 2

Does type of bleed point to a disorder (primary, secondary, both)?

Question 3

What is the workup of a patient for bleeding disorders according to lab testing (definitive test)?

Answer 3

• Manual (tilt tube) → “endpoint”
• Mechanical (Fibrometer, Start4) → “endpoint”
• Photo-optical (MLA, Coag-a-Mate, MDA II) → “endpoint”
• Chromogenic (Protein C assay) → measures proteins that don’t form a fibrin clot as an endpoint
• Immunological → Ag-Ab rxn

Question 4

What type of bleeding is seen w/ a platelet and/or vascular disorder?

Answer 4

???

Question 5

What type of bleeding is seen w/ a coagulation disorder?

Answer 5

???

Question 6

What is the workup of a patient for bleeding disorders according to lab testing (screening tests)?

Answer 6

• Platelet Count
• Bleeding Time
• Prothrombin Time
• INR
• APTT
• Activated Clotting Time (ACT)
• Thrombin Clotting Time (TCT or TT)

Question 7

Prothrombin Time (PT)
- Principle

Answer 7

• Tissue thromboplastin (containing Ca2+) is added to patient plasma
• Measures the time it takes for a clot to form

Question 8

Prothrombin Time (PT)
- Method of activation

Answer 8

Addition of reagent: tissue thromboplastin + Ca2+

Question 9

Prothrombin Time (PT)
- Factors being measured

Answer 9

Extrinsic pathway: VII, X, V, II, I

Question 10

Prothrombin Time (PT)
- Factor deficiencies/conditions yielding abnormal/↑/prolonged results

Answer 10

• Deficiency of factor(s) VII, X, V, II, I
• Liver disease
• Vitamin K deficiency
• Coumadin anticoagulant therapy
• Excessive amounts of heparin
• “Circulating anticoagulants” aka “inhibitors to coagulation”
• DIC

Question 11

Prothrombin Time (PT)
- Reference range

Answer 11

10-13 seconds

Question 12

Activated Partial Thromboplastin Time (APTT)

- Principle

Answer 12

A phospholipid substitute for platelets (“partial thromboplastin”) along with a negatively charged particulate activator is added to patient plasma to activate contact factors
- Ca2+ is re-added (re-calcification) and time required to clot is measured

Question 13

Activated Partial Thromboplastin Time (APTT)

- Method of activation

Answer 13

Particulate activator (negatively-charged surface)

• Elagic acid
• Kaolin
• Silica
• Celite

Question 14

Activated Partial Thromboplastin Time (APTT)

- Factors being measured

Answer 14

Intrinsic pathway: XII (Fletcher and Fitzgerald), XI, IX, VIII, X, V, II, I

Question 15

Activated Partial Thromboplastin Time (APTT)

- Factor deficiencies/conditions yielding abnormal/↑/prolonged results

Answer 15

• Deficiency of factor(s)
• Liver disease
• Heparin anticoagulant therapy
• Long term Coumadin anticoagulant therapy
• “Circulating anticoagulants” aka “inhibitors to coagulation”
• DIC

Question 16

Activated Partial Thromboplastin Time (APTT)

- Reference range

Answer 16

20-35 seconds

Question 17

Activated Clotting Time (ACT)

- Principle

Answer 17

An activator is added to fresh whole blood and clotting time is measured (used in surgery to monitor heparin therapy)

Question 18

Activated Clotting Time (ACT)

- Method of activation

Answer 18

Diatomaceous earth

Question 19

Activated Clotting Time (ACT)

- Factors being measured

Answer 19

Heparin inactivated serine proteases in the intrinsic pathway: XIIa, Fletcher, XIa, IXa, Xa, Thrombin

Question 20

Activated Clotting Time (ACT)

- Factor deficiencies/conditions yielding abnormal/↑/prolonged results

Answer 20

?

Question 21

Activated Clotting Time (ACT)

- Reference range

Answer 21

100-125 seconds

- Minimal ACT desired during bypass is 400 seconds

Question 22

International Normalized Ratio (INR)

- Definition

Answer 22

The ratio b/w the time it takes normal blood to clot and “Coumadin blood” to clot
- The more coumadin, the higher the INR

Question 23

International Normalized Ratio (INR)

- Anticoagulant therapy that it manages

Answer 23

Manages coumadin anticoagulant therapy (along w/ the prothrombin time)

Question 24

INR

- If on coumadin, implications of an INR < 2

Answer 24

At risk to form a new clot

Question 25

INR

- If on coumadin, implications of an INR > 4

Answer 25

Bleeding risk

Question 26

INR

- If not on coumadin, INR range

Answer 26

0.93-1.13

Question 27

Thrombin Clotting Time

- Principle

Answer 27

The reagent thrombin is added to plasma and the time required for clot formation is measured

Question 28

Thrombin Clotting Time

- Conditions yielding ↑/prolonged results

Answer 28

• Afribrinogenemia, Hypofibrinogenemia, Dysfibrinogenemia
• “Antithrombins” (Heprin and FDPs)
• “Circulating anticoagulants”
• DIC
• Thrombin inhibitors (Pradaxa)
• NOT COUMADIN

Question 29

Thrombin Clotting TIme

- Purpose of substituting reptiles for thrombin (Reptilase time)

Answer 29

It is capable of converting fibrinogen to fibrin (like thrombin) but it is unaffected by heparin
- So it is helpful in testing for functional fibrinogen when the TCT is prolonged due to heparin

Question 30

How is an INR calculated?

Answer 30

Patient PT result (in seconds) ÷ mean control PT value (in seconds)