People who have had a clot are often told that "all the tests were done" or that "there's a genetic test for that", and neither is usually true in the way they imagine. This chapter is the full list: the tests everyone should have, the ones the three-month review should include, the thrombophilia and genetic tests with what each one means, the extended tests for unusual clots, and the tests that are sold but not worth doing. It applies to a DVT and a pulmonary embolism alike; the blood clots topic links here rather than repeating it.
1. Tier one: at diagnosis, everyone
| Test | Why | What an abnormal result can mean |
|---|---|---|
| Full blood count | Baseline before anticoagulation (NG158 1.3.4) | Low platelets: bleeding risk, or antiphospholipid syndrome, or heparin-induced thrombocytopenia if on heparin. Very high haemoglobin or platelets: a possible myeloproliferative neoplasm (tier four). Anaemia: bleeding, or cancer |
| Kidney function (creatinine, eGFR, and creatinine clearance calculated from weight) | Chooses the anticoagulant and its dose | Clearance under 30 restricts most DOACs; under 15 excludes them. Protein in the urine with low albumin points to nephrotic syndrome, which loses antithrombin and causes clots |
| Liver function | Baseline; drug choice | Severe liver disease restricts DOACs and lowers the clotting proteins measured in tier three; a clot in the liver veins needs its own workup |
| Clotting screen (PT or INR, APTT) | Baseline before the first dose | A prolonged APTT before any anticoagulant, in someone who clots rather than bleeds, is the classic clue to a lupus anticoagulant |
| D-dimer | Diagnosis only, and only in the "unlikely" arm of the pathway | Has no role after the diagnosis is made; a raised level later does not mean the clot is back |
| Troponin, BNP, lactate, blood gas | Severity of a pulmonary embolism, not the diagnosis | See the hospital checklist |
| Glucose | Routine | Undiagnosed diabetes is common and changes the long-term picture |
| Pregnancy test | Anyone who could be pregnant | Changes the drug (heparin, not tablets), the imaging and the follow-up |
| Urinalysis | Cheap and often omitted | Blood: kidney or bladder cancer to exclude. Protein: nephrotic syndrome |
| Calcium, CRP or ESR | Not required by NG158; commonly added | A high calcium or a high inflammatory marker with no infection is a cancer or inflammatory-disease clue and prompts examination, not a scan |
None of these results is waited for before the first dose. They are reviewed within 24 hours and the drug adjusted if they demand it.
2. Tier two: the three-month review, after an unprovoked clot
The purpose of this tier is cancer, and the evidence is that a careful clinical assessment finds what a body scan finds (see the after-hospital chapter). NICE's list (1.8.1): the history, a physical examination, and a review of the tier-one bloods. In practice that should mean:
- Weight and any weight loss; appetite; night sweats; a change in bowel habit; a cough that has not gone; a new lump; unexplained bleeding from anywhere.
- Examination of the chest, abdomen, lymph nodes, breasts, testes or prostate, and skin.
- Repeat full blood count, liver function, kidney function; urinalysis; calcium if not done.
- Screening programmes brought up to date for the person's age: bowel (FIT test, 50 or 54 to 74 depending on nation), breast (50–70), cervical (25–64), abdominal aortic aneurysm (men at 65), and lung screening for current and former heavy smokers aged 55–74 where the programme has reached their area.
- Not routinely: CT of the chest, abdomen and pelvis, tumour markers (PSA, CA-125, CEA, CA19-9), endoscopy, or mammography outside the programme. Each generates false alarms and none finds more cancer than the examination does. Any of them is done when a symptom or sign points to it, through the suspected-cancer pathway.
3. Tier three: thrombophilia, and what each test means
Ordered only when the result would change the plan (NG158 1.9): after an unprovoked clot when stopping anticoagulation is being considered, or where a family pattern makes a high-risk inherited deficiency plausible. Not after a provoked clot; not in someone who will continue anticoagulation regardless; not routinely in relatives. When it is ordered, this is what is on the form.
| Test | What it detects | How common; how much it raises risk | What a positive result changes |
|---|---|---|---|
| Lupus anticoagulant (a clotting-based test, two methods) | Antiphospholipid syndrome: an acquired autoimmune tendency to clot in veins and arteries, and to lose pregnancies | Around 1 in 10 people with an unprovoked clot has some antiphospholipid antibody; persistent triple positivity is much rarer and carries the highest recurrence risk of any thrombophilia | Continue anticoagulation, and if triple-positive use warfarin rather than a DOAC (the TRAPS trial, and NG158 1.3.20). A positive result must be repeated at least 12 weeks later to count. Changes pregnancy management completely |
| Anticardiolipin antibodies (IgG and IgM) | — | ||
| Anti-β2-glycoprotein I antibodies (IgG and IgM) | — | ||
| Factor V Leiden (a genetic test; some laboratories screen first with an "activated protein C resistance" clotting test) | A variant that makes factor V resistant to being switched off | The commonest inherited thrombophilia: about 1 in 20 people of European ancestry carry one copy, which raises first-clot risk roughly 3–5 fold; two copies (rare) raise it far more. Its effect on recurrence is modest | Rarely the duration of treatment on its own. Firms up advice never to use combined oestrogen, prophylaxis in pregnancy and after surgery, and counselling for relatives |
| Prothrombin G20210A (genetic) | A variant that raises prothrombin levels | About 1 in 50 of European ancestry; raises first-clot risk 2–3 fold; modest effect on recurrence | As for factor V Leiden. Carrying both variants is more significant |
| Antithrombin activity | Deficiency of the protein that heparin works through | Rare, about 1 in 2,000–5,000; the highest-risk inherited deficiency, raising clot risk 10–20 fold, with clots often before 40 | Usually long-term anticoagulation; heparin may work less well ("heparin resistance"); antithrombin concentrate around surgery and childbirth; selective testing of first-degree relatives is reasonable (BSH 2022) |
| Protein C activity | Deficiency of a natural anticoagulant | About 1 in 300–500; raises risk several-fold | Often long-term anticoagulation; starting warfarin needs heparin cover to avoid skin necrosis; selective relative testing |
| Protein S (free antigen, and activity) | Deficiency of protein C's cofactor | Similar to protein C; the hardest of the three to measure reliably | As for protein C |
| Monogenic thrombophilia gene panel (Genomics England) | Sequencing of the antithrombin, protein C, protein S, factor V, prothrombin and fibrinogen genes, among others | For clots under 40 that were spontaneous or weakly provoked and are also present in a first-degree relative, requested by a haematologist or geneticist | Confirms a deficiency found on activity testing, explains a strong family history, and allows cascade testing of relatives who want it |
The timing rules, which is where most of these tests go wrong. Antithrombin is lowered by heparin and by the clot itself. Protein C and protein S are lowered by warfarin, the acute clot, liver disease, pregnancy and oestrogen. The lupus anticoagulant test gives false results on heparin, warfarin and especially DOACs, and the clotting-based screen for factor V Leiden is unreliable on DOACs too. So: the clotting-based tests are done four to six weeks after anticoagulation stops, or with the laboratory's advice on neutralising the drug in the sample; the genetic tests can be done at any time; and a low protein C, protein S or antithrombin found in hospital is repeated before anyone is told they have a deficiency. Positive antiphospholipid tests are repeated at twelve weeks before the diagnosis is made.
4. Tier four: extended tests for unusual, young or recurrent clots
Justified by a clot in an unusual site (arm, abdomen, brain veins), clots at a young age, clots in both arteries and veins, a clot despite anticoagulation, an abnormal blood count, or features of another disease. Ordered through a haematologist.
| Test | Looks for | When | What it changes |
|---|---|---|---|
| JAK2 V617F mutation (then CALR and MPL if negative) | A myeloproliferative neoplasm, which can present with a clot before the blood count is abnormal | Any abdominal or brain-vein clot; any clot with a raised haemoglobin or platelet count; recurrent unexplained clots | A haematology diagnosis with its own treatment; usually long-term anticoagulation |
| PNH clone (flow cytometry for CD55/CD59 or FLAER) | Paroxysmal nocturnal haemoglobinuria, a rare acquired condition that clots in unusual veins | Abdominal or brain-vein clots; clots with haemolysis or a low blood count | Treatable with a specific antibody drug |
| Autoimmune screen (ANA, anti-dsDNA, complement, ANCA; ESR) | Lupus and other connective tissue disease, vasculitis, Behçet's | Antiphospholipid antibodies positive, or symptoms: rash, joint pain, mouth ulcers, eye inflammation, fever | Rheumatology referral; immunosuppression treats the cause |
| Urine protein-to-creatinine ratio and serum albumin | Nephrotic syndrome (loses antithrombin in the urine) | Protein on the dipstick; swollen ankles | Renal referral; the clot risk falls when the kidney disease is treated |
| Myeloma screen (serum protein electrophoresis, free light chains) | Myeloma and related conditions, which thicken the blood | Older people with unexplained clots, bone pain, anaemia or high calcium | Haematology diagnosis |
| Heparin-induced thrombocytopenia antibodies (anti-PF4) | An immune reaction to heparin that causes clots and a falling platelet count | Platelets fall by half between day 5 and 10 of heparin, or a new clot on heparin | Stop all heparin; use argatroban or fondaparinux; never heparin again |
| Homocysteine | Homocystinuria, a rare inherited metabolic disease | Only with the features: clots young, tall thin build, dislocated lenses, learning difficulty. Not as a routine "risk factor" test: lowering a mildly raised level with vitamins does not prevent clots | Metabolic referral; a specific diet and vitamin treatment |
| Factor VIII level | Persistently high levels associate with clots | Sometimes measured in unexplained recurrence | Nothing specific; it is a research marker more than a clinical one |
| Fibrinogen and thrombin time | Dysfibrinogenaemia, a rare structural defect | Unexplained recurrence with a family history and odd clotting-screen results | Haematology-led |
| Cancer investigation directed by a finding | The cancer the examination or bloods pointed to | Any symptom or sign, a high calcium, blood in the urine, anaemia | The suspected-cancer pathway for that site |
5. Tests that are sold but not worth doing
- MTHFR (C677T, A1298C): a common variant with no clinically significant link to clots. The BSH guideline states outright that it should not be tested for; nor should PAI-1 (SERPINE1) variants.
- "Full thrombophilia screens" ordered on the ward in the first week or on an anticoagulant: half the results will be uninterpretable and need repeating.
- Direct-to-consumer genetic panels that report factor V Leiden or prothrombin status alongside dozens of unvalidated variants: the two real ones are worth knowing only in the situations above, and the rest are noise.
- Homocysteine as a routine risk marker, for the reason above.
- Repeated D-dimers after diagnosis to "check the clot is gone" or to decide on stopping treatment: NICE says not to use D-dimer for that decision.
- Tumour markers and whole-body scans as cancer screening after a clot (tier two).
6. For your relatives
Routine testing of family members is not recommended (NG158 1.9.5; BSH 2022). The exception is a first-degree relative of someone with a confirmed protein C, protein S or antithrombin deficiency, where the result can change decisions about the combined pill, pregnancy and surgery; testing is offered selectively and with counselling. What a relative of anyone who has had a clot should do regardless of testing: mention the family history at every admission, operation and pregnancy; avoid combined oestrogen where an alternative exists; and know the symptoms.
7. The list, in one paragraph, for the review appointment
"Were the baseline bloods normal, including the blood count, kidney, liver and clotting?" "Has a physical examination been done and is my screening up to date?" If stopping anticoagulation is being discussed after an unprovoked clot: "Should antiphospholipid antibodies be tested, and if a relative has had a clot, should the inherited tests be done, and when, given my treatment?" If the clot was in an unusual place or you are under 40: "Have JAK2 and PNH been tested, and have I been referred to haematology?" And if anyone offers MTHFR or a full panel on the ward: "What would that result change?"
8. Where UK and US guidance differ
The American Society of Hematology's 2023 guideline and the BSH's 2022 guideline reach the same conclusions: test when it changes management, not routinely; nothing for MTHFR or PAI-1; mind the timing. The US guideline is slightly more willing to suggest testing after a clot provoked by hormones or a minor trigger, where a positive result would tip a borderline stopping decision, and US laboratories run wider panels by default. NICE's rules are the narrowest of the three and are the ones that apply on the NHS.