Point-of-Care INR

Point-of-care (POC) INR testing measures the international normalised ratio, a standardised prothrombin time ratio, from a finger prick sample of whole blood on handheld coagulometers (several commercial models). The strip contains thromboplastin and a clot detection electrochemical or optical method, and gives the INR in 1 to 2 minutes.

It is calibrated to the international sensitivity index of the thromboplastin and to laboratory plasma methods, and is validated for monitoring vitamin K antagonist therapy (warfarin, acenocoumarol, phenprocoumon) in the range 2.0 to 4.5.

POC devices tend to overestimate INR at values over 4.0 to 4.5 and in antiphospholipid syndrome, so high or unexpected values are confirmed by venous laboratory testing.

Oral anticoagulants are used by 1 to 2% of adults in high income countries, mostly for atrial fibrillation, venous thromboembolism and mechanical heart valves. Warfarin remains the only suitable drug for mechanical mitral and aortic valves, rheumatic mitral stenosis with atrial fibrillation, and antiphospholipid syndrome, and is widely used in low income countries.

Time in therapeutic range (target over 65 to 70%) is the main measure of quality, and each 10% rise reduces major bleeding and thromboembolism. Self-testing and self-management with POC devices improve time in therapeutic range and reduce thromboembolism compared with routine care.

Indications. Monitoring warfarin or other vitamin K antagonists in clinic, pharmacy, ward, home or remote settings. Dose adjustment after initiation, drug interactions, illness, or diet change. Patients with mechanical valves, recurrent thromboembolism, and unstable control.

Rapid check before invasive procedures, in emergencies (stroke, bleeding, trauma), and in obstetric haemorrhage. Not for monitoring direct oral anticoagulants (INR is insensitive), heparin or low-molecular-weight heparin, and not for diagnosis of coagulopathy in liver disease or disseminated intravascular coagulation without laboratory confirmation.

Specimen. Fresh capillary blood from the side of the fingertip (wash and dry hands, avoid alcohol residue, no squeezing, apply the first drop, one drop to the strip within 1 to 2 minutes of lancing), or venous whole blood without anticoagulant where the device allows. Use strips within date and in the lot calibration (code chip). Store strips at the correct temperature. Record the time of last warfarin dose and the current dose.

Reference values. INR 0.8 to 1.2 in people not on anticoagulants. Therapeutic range on warfarin: INR 2.0 to 3.0 (target 2.5) for atrial fibrillation, venous thromboembolism, bioprosthetic valves and most indications; 2.5 to 3.5 (target 3.0) for mechanical mitral valves, mechanical aortic valves with risk factors, and recurrent thromboembolism on therapy.

Interpretation.

• INR within range: continue the current dose and repeat at the planned interval (up to every 12 weeks in stable patients).
• INR just under range (1.5 to 1.9 for a target of 2.0 to 3.0): increase weekly dose by 5 to 20% and consider bridging in high risk patients (mechanical valve, recent stroke or embolism); check adherence and diet (vitamin K intake).
• INR over range up to 4.5: omit one dose or reduce the weekly dose by 5 to 15%, and recheck within a week.
• INR 4.5 to 10 without bleeding: omit warfarin for 1 to 2 doses and consider oral vitamin K 1 to 2.5 mg if the risk of bleeding is high; INR over 10 without bleeding: oral vitamin K 2.5 to 5 mg.
• Any INR with major bleeding: stop warfarin, give prothrombin complex concentrate and intravenous vitamin K 5 to 10 mg, and use fresh frozen plasma only if concentrate is unavailable.
• Unexpectedly high INR: acute illness (heart failure, fever, diarrhoea, liver disease, thyroid overactivity), drug interactions (antibiotics, azoles, amiodarone, allopurinol, paracetamol at high doses), reduced vitamin K intake, alcohol binge, or acute weight loss.
• Persistently low INR despite high doses: poor adherence, increased vitamin K in diet, enzyme inducing drugs (rifampicin, carbamazepine, phenytoin), or genetic resistance (VKORC1).
• Lupus anticoagulant and antiphospholipid antibodies prolong the baseline INR and cause overestimation with POC devices; laboratory chromogenic factor X is then used.

Critical values and findings needing immediate action.

• INR over 5.0 with bleeding, or over 8.0 at any time: urgent assessment, vitamin K and in major bleeding reversal with prothrombin complex concentrate.
• INR over 4.5 in a patient with head injury, intracranial bleeding, gastrointestinal bleeding or haematuria: immediate emergency care and reversal.
• INR under 1.5 in a patient with a mechanical mitral valve, recent stroke or acute venous thromboembolism: bridging with low-molecular-weight heparin until therapeutic.
• INR rising rapidly after starting a new drug (antibiotic, antifungal, amiodarone): dose reduction and early retesting in 2 to 3 days.
• Pregnant woman on warfarin: stop and switch to heparin because of embryopathy (6 to 12 weeks) and foetal bleeding, with specialist input for mechanical valves.
• INR over 1.5 before surgery: plan vitamin K and timing of surgery as the urgency requires.

Interferences and pitfalls.

• Haematocrit outside 25 to 55% (polycythaemia, severe anaemia), poor sampling (first drop contaminated with tissue factor, squeezing, delay in applying), and cold fingers cause errors.
• Antiphospholipid antibodies, lupus anticoagulant, liver disease, factor deficiencies, heparin, direct thrombin and factor Xa inhibitors, and some dyslipidaemias affect results. POC INR is less reliable in those with baseline prolonged INR.
• At INR over 4.5, POC devices read higher than laboratory values; confirm with venous plasma testing before a dose change or reversal.
• Differences between devices and lots; the same device and strip should be used for follow up.
• Strips damaged by heat, humidity, or expiry, and the wrong code chip, give errors; liquid controls are used regularly.
• Poor timing of the test relative to the dose, missed doses and inaccurate records cause inappropriate dose changes.
• Patient education (diet, alcohol, drug interactions, bleeding and clot signs, carrying an anticoagulation card) determines safety.
• Direct oral anticoagulants are preferred for atrial fibrillation and venous thromboembolism, but not in mechanical valves, severe renal failure, antiphospholipid syndrome or moderate to severe mitral stenosis.
• Monitoring in remote settings needs reliable supply, record keeping and referral for high or unstable values.

Special groups.

• Elderly patients: higher bleeding risk, variable diet, polypharmacy, and falls.
• Children: used for mechanical valves and thrombosis, with age related reference ranges and difficulty with sampling.
• Pregnancy: avoid warfarin in the first trimester and near term; low-molecular-weight heparin is the alternative.
• Liver disease and malnutrition: increased sensitivity to warfarin and low vitamin K stores.
• Peri-operative patients: bridging decisions depend on thrombotic risk.
• Regions: warfarin is the only available oral anticoagulant in many low income settings, and rheumatic heart disease with mitral stenosis, atrial fibrillation and mechanical valves create high demand for monitoring; POC INR in community clinics and self-testing increases time in range.

Follow up tests. Venous laboratory INR when POC is out of range or in antiphospholipid syndrome, full blood count, liver function, creatinine and eGFR, drug and diet review, thyroid function, antiphospholipid antibodies, echocardiography in valve disease and atrial fibrillation, genotype testing (CYP2C9, VKORC1) in resistance or sensitivity, stool occult blood, imaging for suspected bleeding, and monitoring of time in therapeutic range.