Coagulation cascade
- intrinsic: factor XI, IX (measured with APTT, see below), extrinsic: factor VII (measured with PT, see below), common: factor X, V and II
- vitamin K dependent: factor VII, IX, X and II
- factor XII is not needed in coagulation cascade, but needed in laboratory
Measurements
- Using instruments such as ACL (Instrumentation laboratory) that measures among other chromogenic (absorption of the light of the coagulation).
- APTT:
- reagentia used should activate contact, for example silica, moreover cofactor such as Calcium is needed.
- PT:
- reagentia in the past was tissue (for example brain)
- antiheparine in reagentia.
- results can be measured in time and converted in % using calibration curve (normal is 100%, > 70% is International normalized ratio (INR) around 1.3)
- INR is measured by (PT of patient/ PT od reference) powered by International Sensitivity Index.
- PT is shorter than APTT (less factors to be activated)
- Fibrinogen
- QFA by adding trombin.
How to interpret PT and APTT increase
- When APTT is increased, think of factor deficiency --> perform a mix test (50% patient's sample 50% sample from normal person --> normalized: factor deficiency, not: inhbition (i.e. lupus anticoagulans, beeing ill).
- When PT is increased, think of factor VII deficiency.
- When both is increased, determine the factors from the common pathway: factor X, V and II.
Thrombophilia
- From higher to lower incidence: prothrombin gene mutation, antithrombin deficiency, Protein C and Protein S deficiency.
- Clinical relevant, mostly when the factor lower than 50%.
- Protein S is associated with hormones.
Oral anticoagulants
- Endeavour INR is 2-3 or 2.5 to 3.5 in mechanical valve. INR in normal person: 1.
Acenocoumarol (Sintrom)
- short t 1/2: 10 hours
- 1 tablet is 1 g
- adjustment:
- find first the reason why the INR is not reached.
- 5 to 10% adjustment.
- see the patient back in 1 week (for example too low, too high value), in 6 weeks (good value) or in between.
- booster dose can be given.
If the INR is really high >5
- ask what the probable cause:
- more alcohol
- diarrhea (due to loss of vitamine K)
- medication (antibiotics, cholesterol lowering drugs, antacid)
- skip the oral anticoagulants for 2 days and start with lower regime
the INR is low
- ask what the probable cause:
- compliance
- diarrhea
bridging oral anticoagulant in case of surgery
- stop acenocoumarol for 3 to 4 days prior to surgery, warfarin for 7 days.
- use fraxiparine in these days but nothing on the surgery day.
- restart oralanticoagulant together with fraxiparine for 4 days (acenoucoumarol) or 7 days (warfarin).
New oral anticoagulant
- one size fits all. Only one dose available and no PT (INR) control is needed.
- anti factor X (i.e. rivaroxaban, it can give PT increase) and anti factor II (i.e. dabigatran, it can give APTT increase).
Trivia
- Pregnancy and oral anti conceptiva can lower protein C.
- Factor V Leiden, mutation therefore this factor cannot be inhibit by activated factor C (APC).
- Corticosteroids is 'trombophile'.
- In dialysis patients, heparin is often used --> measure PT and APTT because the blood is often contaminated with heparine. If only PT is measured, this can be high but it cannot be derived whether this is falsely increased (very high APTT due to heparine contamination can also caue high PT).
- intrinsic: factor XI, IX (measured with APTT, see below), extrinsic: factor VII (measured with PT, see below), common: factor X, V and II
- vitamin K dependent: factor VII, IX, X and II
- factor XII is not needed in coagulation cascade, but needed in laboratory
Measurements
- Using instruments such as ACL (Instrumentation laboratory) that measures among other chromogenic (absorption of the light of the coagulation).
- APTT:
- reagentia used should activate contact, for example silica, moreover cofactor such as Calcium is needed.
- PT:
- reagentia in the past was tissue (for example brain)
- antiheparine in reagentia.
- results can be measured in time and converted in % using calibration curve (normal is 100%, > 70% is International normalized ratio (INR) around 1.3)
- INR is measured by (PT of patient/ PT od reference) powered by International Sensitivity Index.
- PT is shorter than APTT (less factors to be activated)
- Fibrinogen
- QFA by adding trombin.
How to interpret PT and APTT increase
- When APTT is increased, think of factor deficiency --> perform a mix test (50% patient's sample 50% sample from normal person --> normalized: factor deficiency, not: inhbition (i.e. lupus anticoagulans, beeing ill).
- When PT is increased, think of factor VII deficiency.
- When both is increased, determine the factors from the common pathway: factor X, V and II.
Thrombophilia
- From higher to lower incidence: prothrombin gene mutation, antithrombin deficiency, Protein C and Protein S deficiency.
- Clinical relevant, mostly when the factor lower than 50%.
- Protein S is associated with hormones.
Oral anticoagulants
- Endeavour INR is 2-3 or 2.5 to 3.5 in mechanical valve. INR in normal person: 1.
Acenocoumarol (Sintrom)
- short t 1/2: 10 hours
- 1 tablet is 1 g
- adjustment:
- find first the reason why the INR is not reached.
- 5 to 10% adjustment.
- see the patient back in 1 week (for example too low, too high value), in 6 weeks (good value) or in between.
- booster dose can be given.
If the INR is really high >5
- ask what the probable cause:
- more alcohol
- diarrhea (due to loss of vitamine K)
- medication (antibiotics, cholesterol lowering drugs, antacid)
- skip the oral anticoagulants for 2 days and start with lower regime
the INR is low
- ask what the probable cause:
- compliance
- diarrhea
bridging oral anticoagulant in case of surgery
- stop acenocoumarol for 3 to 4 days prior to surgery, warfarin for 7 days.
- use fraxiparine in these days but nothing on the surgery day.
- restart oralanticoagulant together with fraxiparine for 4 days (acenoucoumarol) or 7 days (warfarin).
New oral anticoagulant
- one size fits all. Only one dose available and no PT (INR) control is needed.
- anti factor X (i.e. rivaroxaban, it can give PT increase) and anti factor II (i.e. dabigatran, it can give APTT increase).
Trivia
- Pregnancy and oral anti conceptiva can lower protein C.
- Factor V Leiden, mutation therefore this factor cannot be inhibit by activated factor C (APC).
- Corticosteroids is 'trombophile'.
- In dialysis patients, heparin is often used --> measure PT and APTT because the blood is often contaminated with heparine. If only PT is measured, this can be high but it cannot be derived whether this is falsely increased (very high APTT due to heparine contamination can also caue high PT).
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