Coagulation tests Flashcards
What pathway is affected if only APTT prolonged
Intrinsic or common
What pathway is affected if only PT prolonged
Extrinsic
What pathway is affected if both APTT and PT prolonged
Common pathway
What factors are part of intrinsic pathway
12,11,9,8
Count down from 12 missing 10
What factor represents extrinsic pathway
VII/7
Common pathway factors
I,II,V,X
What factor joins extrinsic and intrinsic pathways
X
Clotting cascade end
X+V - Ca2+ + lipids -> thrombin –prothrombin –> fibrinogen -> fibrin clot
Causes of isolated prolonged PT
Isolated vit K deficiency (early stages)
Liver disease (early stages)
Warfarin in therapeuti range - INR
Congenital and acquired FVII deficiency
Prolonged APTT
Lupus anticoagulant - misnomer
Unfractionated heparin
Congenital intrinsic factor deficiency
Acquired intrinsic factor inhibitors/acquired haemophilia
What is lupus anticoagulant
Misnomer - prolongs APTT
Not ass w increased bleeding risk - increased VTE risk
Ass transient transfusion, SLE, antiphospolipid syndrome
What factor deficiency causes haemophilia A
FVIII
What facotr deficiency causes haemophilia B
FIX
How to test for factor deficiencies singular vs multiple
50:50 mix blood test
1:1 patient blood and normal blood
What does non correction in the 50:50 bmix blood test show?
Specific or non specific inhibitor OR
multiple factor deficiencies
What does a correction of 50:50 mix tes suggest
Single factor deficiency as normal blood can provide the missing factor
Causes of combined prolonged APTT and PT
Severe vit K deficiency
Advance liver disease
DOACs
Supratherapeutic warfarin therapy
Factor consumption eg DIC
Congenital common pathway factor deficiency, acquired inhibitors to common pathway factors
What screening test can differentiate DIC, vit K deficiency/warafrin use and liver disease
Factor V, VII and VIII
Why do mild vit K def and early stage liver disease only prolong PT
Factor VII has shorter half life than other factors - first one to be affected
Why is DOAC monitoring unreliable
Prolonging of APTT and PT depends when checked, cant tell if tehrapuetic or not from levels
How is APTT measured
Incubate citrated plasma with contact activator first
ADD phospholopid and calcium - time for clot formation in seconds
What test for if low factor VIII
VWD screen
What does a normal VWD screen suggest
Haemophilia A
What does abnormal VWD screen suggest
Von willebrand disease
What test do if corect 50/50 mi and normal factor levels
Long incubation APTT for early contact factor deficiency
What time is not correcting for 50/50 mix
> 41 seconds
If non correction 50/50 mix and then non specific inhibitor what test for
Antiphospholipid antibody testing
What test do if consistent with inhibitor after non correction of 50/50 mix
Inhibitor assay for factor that is decreased
50/50 mix how works
APTT reported within 5 minutes of the mix (“immediate”)
after 60 minutes incubation at 37°C -detect progressive inhibitor (this usually indicates a factor VIII inhibitor)
What would find if factor VIII inhibitor on 50/50 mix
Progressive inhibitor after 60 mins incubation
What causes signiicantly prolonged APTT (>100s) but no bleeding
Contact factor deficiency (prekallikeren, HMW kininogen)+factor XII
What is INR
Standardised PT
What is ISI
International Sensitivity Index (indicates sensitivity of reagent to deficiencies in Vitamin K dependent factors compared to the WHO reference standard)
Prolonged PT tests to order after
Liver enzymes, albumin, bilirubin
50/50 mix for correction
What suspect if correction of 50/50 in prolonged PT
Deficiencies
What suspect if non-correction of 50/50 in prolonged PT
Specific or non sepcific inhibitors to Factor VII
Differentials for prolonged APTT AND PT
- Thrombin inhibitors (heparin, direct thrombin inhibitors or direct Xa inhibitors)
- Vitamin K deficiency (including use of Vitamin K antagonists)
- DIC
- Liver disease
- Paraproteinemia
- Congenital factor II, V, X or fibrinogen deficiencies
- Fibrinogen depletion (hemodilution, massive hemorrhage, fibrinolysis)
- Dysfibrinogenemia (acquired vs congenital)
- Acquired factor X deficiency from amyloidosis
- Acquired factor V inhibitors topical bovine thrombin, postoperatively, post-cardiac bypass
- Any common pathway factor inhibitors
Differentiating between factor V, factor VII and factor VIII
V - NOT vit K dependent, only made in liver, common
VII - Vit K dependent, only made by liver, exrinsic
VIII -NOT vit K dependent, Lliver and endothelial cells make, intrinsic
Why can FVIII be elevated in disorders such as liver disease
Acute phase reactant
