Coagulation Tests Flashcards
(13 cards)
APTT
Purpose:
* Assesses the intrinsic pathway and final common pathway.
Factors Involved:
* Intrinsic: Factors XII, XI, IX, VIII
* Common: Factors X, V, II (prothrombin), I (fibrinogen)
Test Mechanism:
* Requires:
* Negatively charged particles (e.g., kaolin)
* Phospholipid + Calcium
* Simulates collagen exposure in injured tissue
Note:
* APTT does not detect extrinsic pathway defects (e.g., Factor VII).
PT and INR
- PT (Prothrombin Time)
Purpose:
* Assesses the extrinsic pathway and final common pathway of the coagulation cascade.
Factors Tested:
* Vitamin K–dependent factors: II, V, VII, X (except IV)
* Factor VII is key for extrinsic pathway and has a short half-life → very sensitive to vitamin K status.
Pathway Flow:
* Tissue Factor (extrinsic trigger) → Factor VII → Factor X → Prothrombin → Thrombin → Fibrin
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- INR (International Normalized Ratio)
Purpose:
* Standardized version of PT; allows comparison between labs.
Interpretation:
* INR of 2 = blood clots twice as slowly as normal.
Mixing studies
Purpose:
* Used to distinguish between factor deficiencies and factor inhibitors in patients with prolonged PT or APTT.
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How It Works:
1. If a sample has a high PT or APTT, add normal plasma to it in a 50:50 ratio.
2. Interpretation:
* If an inhibitor is present:
* It will inhibit the normal plasma too.
* The result will remain abnormal.
* If a deficiency is present:
* Normal plasma provides the missing clotting factors.
* The result will return to normal.
Note: Only 50% of the clotting factors are typically sufficient to normalize a PT or APTT result.
ACT
Activated Clotting Time
Function:
* Tests the entire clotting cascade, including:
* Activation of clotting factors
* Formation of fibrin
Test Procedure:
* Fresh blood is mixed with glass beads or kaolin balls.
* The time taken to form clot is calculated.
Purpose:
* Performed at the bedside to monitor anticoagulation during:
* Bypass surgery
* ECMO circuits
Reference Values:
* Normal ACT: 100–110 sec
(approx. 4–6× clotting time)
* Bypass circuit target: 400–600 sec
* ECMO circuit target: 200–300 sec
(approx. 2–3× clotting time)
Causes of Prolonged ACT:
1. Thrombocytopenia
2. Clotting factor deficiency
3. Clotting factor inhibitors
4. Low fibrinogen
5. Hypothermia
6. Heparinisation
Thrombin Time
Definition:
* Measures the final step of the clotting cascade:
* Thrombin converts fibrinogen → fibrin
Key Inhibitor:
* This step is antagonized by Antithrombin III
(especially in the presence of Heparin)
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Causes of Prolonged Thrombin Time:
1. Heparin therapy
2. Low fibrinogen level
3. Dysfunctional fibrinogen (e.g., congenital or acquired)
4. Direct thrombin inhibitors:
* Argatroban
* Dabigatran
5. Amyloidosis
6. Very high fibrinogen levels
→ Can paradoxically prolong TT
Reptilase Time
Definition:
* Reptilase is an enzyme secreted by the Pit viper.
* Like thrombin, it catalyzes the cleavage of fibrinogen → fibrin, initiating clot formation.
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Key Difference from Thrombin:
* Not affected by:
* Heparin
* Antithrombin III
* Direct thrombin inhibitors
(e.g., in APS – antiphospholipid syndrome)
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Uses:
* Helps differentiate between heparin effect and true fibrinogen abnormalities.
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Prolonged Reptilase Time Seen In:
1. Low fibrinogen levels
2. Abnormal fibrinogen
3. Very high fibrinogen levels
4. Amyloidosis
5. High levels of paraproteins/fibrin degradation products
Increased PT and Normal APTT
→ Extrinsic pathway failure
Causes:
* Warfarin therapy
* Vitamin K deficiency
* Liver disease
* Isolated Factor VII deficiency
Increassed APTT & Normal PT
→ Intrinsic pathway failure
Causes:
* Factor deficiencies:
* VIII (Hemophilia A)
* IX (Hemophilia B)
* XI (Hemophilia C)
* XII (rare, asymptomatic)
* von Willebrand Disease
* Factor inhibitors
* Anticoagulants (e.g., heparin)
To further clarify, perform Mixing studies- If APTT normalises- factor deficiency, if remains abnormal- Inhibitor present
If abnormal mixing studies- differentiate among causes with TT and RT
If Mixing Studies Are Abnormal:
→ Suggests anticoagulant factor or inhibitor
Use TT (Thrombin Time) & RT (Reptilase Time) to differentiate:
* Normal TT & RT:
* Antiphospholipid antibody
* TT ↑ & RT Normal:
* Heparin therapy
* Heparin-like anticoagulants
* Direct thrombin inhibitors (e.g., malignancy-related)
* TT ↑ & RT ↑:
* Low or abnormal fibrinogen
* Paraproteinemia
* Excess FDPs
* Amyloidosis
- Isolated ↑ PT – Causes:
- Vitamin K deficiency
- Liver disease (due to impaired Vit K storage or synthesis)
- Warfarin therapy
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Distinguishing Between These: Use Ecarin Clotting Time (ECT):
Distinguishing Between These: Use Ecarin Clotting Time (ECT):
* ECT bypasses prothrombin → fibrin by skipping intrinsic & extrinsic pathways.
* Not affected by warfarin or heparin.
* Used to measure activity of direct thrombin inhibitors.
* In severe liver disease, thrombin is not synthesized → ECT is prolonged.
Isolated Increase in APTT
Isolated ↑ APTT
Possible Causes:
* Intrinsic pathway inhibition:
* Factor deficiency or dysfunction:
* Factors VIII, IX, XI, XII
* Von Willebrand disease
* Disseminated intravascular coagulation (DIC)
* Factor inhibitors:
* Heparin
* Antiphospholipid syndrome (APLS)
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Discriminating Between Deficiency vs Inhibitor:
* Use Mixing Studies:
* Correction → suggests deficiency
* No correction → suggests inhibitor
APTT + Abnormal Mixing Study – Differentials and workup
APTT + Abnormal Mixing Study – Differentials:
1. Heparin
2. Heparin-like anticoagulants
3. Antiphospholipid syndrome (APLS)
4. Multiple myeloma
5. Thrombotic states
6. DIC (due to low clotting factors and ↑ FDPs)
Workup for ↑ APTT with Abnormal Mixing Studies (Page 23):
- Test for:
- Antiphospholipid antibodies
- Heparinase assay:
- Neutralizes heparin
- Reverses heparin-induced coagulo
pathy
. Compare Thrombin Time (TT) & Reptilase Time (RT):
Cause TT RT
Heparin increase Normal
HEP like anticoag. increase Normal
paraprot. Increase Increase
FDP and Amyloid
Important Note:
* APTT will NOT detect Factor VII deficiency
(Factor VII is part of the extrinsic pathway and affects PT, not APTT)
Causes of Total Coagulopathy
- DIC (Disseminated Intravascular Coagulation)
- ↓ Platelet count due to consumption
2. Snake bite - Can be pro-coagulant or anticoagulant
3. Thrombolysis
4. Primary Fibrinolysis - Normal platelet count
5. Heparin overdose - Fibrinogen levels normal
6. Massive transfusion - Can cause coagulopathy if clotting factors are not adequately replaced
7. Anticoagulation therapy - Includes direct thrombin inhibitors
- ↓ Platelet count due to consumption
