Basic coagulation tests, such as activated partial thromboplastin time (aPTT), D-dimer, fibrinogen levels, international normalised ratio (INR), and prothrombin time (PT)

What the tests measure

Screening tests measure time to clot formation in vitro - they test the initiation phase only
- They say nothing about clot strength, platelet function, fibrinolysis or bleeding risk in vivo

Test	Pathway	Factors measured
PT / INR	Tissue factor ("extrinsic")	VII, X, V, II, fibrinogen
APTT	Contact ("intrinsic")	XII, XI, IX, VIII, X, V, II, fibrinogen
Thrombin time	Fibrinogen -> fibrin	Fibrinogen, thrombin inhibitors
Reptilase time	As TT, snake venom	Fibrinogen only - unaffected by heparin or DTIs
Fibrinogen (Clauss)	-	Functional fibrinogen
D-dimer	Fibrinolysis	Cross-linked fibrin degradation

INR = PT ratio corrected by the reagent ISI - only validated for warfarin; "INR" in liver disease is not comparable

Factor half-lives set how fast each test moves
- VII ~4-6 h -> PT/INR is the first to prolong in warfarin, vitamin K deficiency and liver disease
- II ~60 h, fibrinogen ~4 days
Newborns have physiologically low vitamin K-dependent factors -> longer PT/APTT for the first months
~1 in 30 healthy people have a mildly prolonged APTT on screening - usually lupus anticoagulant or FXII deficiency, not a bleeding disorder

A test prolongs when a factor in its pathway falls below ~30-40% activity
- This is why mild haemophilia and mild VWD have a normal APTT
Prolongation from deficiency vs inhibitor is separated by the mixing study

Corrects -> factor deficiency
Does not correct -> inhibitor
- Immediate non-correction -> lupus anticoagulant or heparin
- Non-correction only after 2 h incubation at 37 degrees -> factor VIII inhibitor (time- and temperature-dependent)

Underfilled citrate tube (excess citrate), heparin contamination from a line, polycythaemia (high haematocrit -> relative citrate excess -> falsely long), clotted or old sample, high bilirubin/lipaemia

Prolonged PT, normal APTT

Normal PT, prolonged APTT

Both prolonged

Both normal but the patient bleeds

*A normal PT and APTT do not exclude a bleeding disorder*
Platelet function disorders, mild von Willebrand disease, factor XIII deficiency, alpha-2-antiplasmin or PAI-1 deficiency, vascular disorders (HHT, Ehlers-Danlos, scurvy), mild/masked factor deficiency

*Factor XII deficiency prolongs the APTT markedly but causes no bleeding* - a laboratory finding only
*Lupus anticoagulant prolongs the APTT in vitro but causes thrombosis in vivo*
Factor VIII is normal or high in liver disease (endothelial synthesis) but low in DIC - the single best discriminator

Fibrin degradation product from plasmin lysis of cross-linked fibrin
- -> a raised level means thrombus has formed and is being lysed, not simply that fibrinogen is being broken down
High sensitivity, poor specificity - use for rule-out in low/intermediate pre-test probability only
- Age-adjusted cutoff: age x 10 microg/L if >50 years
Raised in: VTE, DIC (the most sensitive single marker), pregnancy, sepsis, surgery, trauma, malignancy, AF, aortic dissection, age, renal failure, liver disease

ISTH score: platelets, PT prolongation, fibrinogen, fibrin marker (D-dimer) - >=5 = overt DIC
Pattern: dec platelets, inc PT and APTT, dec fibrinogen, inc D-dimer, dec factor VIII, schistocytes
Fibrinogen is an acute phase reactant - a "normal" fibrinogen in sepsis may be falling and still abnormal. Track the trend

Platelet function analyser / light transmission aggregometry - platelet disorders
VWF antigen, activity (GPIbM/ristocetin cofactor), multimers, factor VIII
Urea clot solubility or FXIII antigen - factor XIII deficiency
Anti-Xa - LMWH, fondaparinux, apixaban/rivaroxaban levels
Dilute thrombin time / ecarin - dabigatran
Thromboelastography/ROTEM - global clot formation and lysis in bleeding and trauma

What each abnormal result actually requires

Finding	Action
Prolonged INR on warfarin, no bleeding	Withhold; vitamin K 1-2 mg oral if INR >4.5-10
Warfarin + major bleeding	Prothrombinex-VF 25-50 IU/kg + vitamin K 5-10 mg IV (+ FFP if unavailable)
Vitamin K deficiency	Vitamin K 10 mg IV/oral; correct cause
DIC	Treat the trigger. Platelets <50 if bleeding, cryoprecipitate if fibrinogen <1.5 g/L, FFP for factor replacement
Isolated prolonged APTT, no bleeding history	Mixing study; check for lupus anticoagulant and FXII before further work-up
Acquired FVIII inhibitor	Bypassing agent (rFVIIa/aPCC) + immunosuppression (steroid + rituximab/cyclophosphamide)
Dabigatran + major bleeding	Idarucizumab
Apixaban/rivaroxaban + major bleeding	Andexanet alfa where available, else Prothrombinex

*Do not "correct" an abnormal number in a non-bleeding patient before a procedure* - FFP for a mildly raised INR in liver disease does not reduce bleeding and causes volume overload and TRALI

Liver disease - rebalanced haemostasis; a raised INR is not a marker of anticoagulation or of bleeding risk
Vitamin K deficiency bleeding of the newborn - reduced II, VII, IX, X with prolonged PT and APTT (distinct from haemolytic disease of the newborn, which is immune haemolysis)
Antiphospholipid syndrome - lupus anticoagulant
Amyloidosis - acquired factor X deficiency
Nephrotic syndrome - antithrombin loss
Massive transfusion - dilution, hypothermia, acidosis, citrate-induced hypocalcaemia (all impair clotting independently of factor levels)

Screening tests were designed to detect factor deficiency, not to predict bleeding - they perform poorly as pre-operative screens in unselected patients
- A structured bleeding history outperforms routine pre-operative coagulation screening
Where the history is positive and the screen normal, escalate to VWF studies, platelet function testing and FXIII - do not stop at a normal APTT

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