How to test for Pernicious Anemia? If you suspect you have PA — which for all practical purposes is an incurable B12 deficiency — you want to know about it quickly. That’s because once permanent neurological damage has kicked it, you won’t be able to revert back to your former self. Therefore, it’s crucial to hurry with Pernicious Anemia diagnosis.
Sadly, in most countries, doctors testing for Pernicious Anemia do a pretty awful job. In a survey done by the Pernicious Anemia Society, 44% of patients were misdiagnosed with another condition; 22% had to wait two years for a correct diagnosis; 19% for five years; 4% for 10 years; and 14% waited 10 years or more. That is a catastrophy.
When you have Pernicious Anemia and wait so much time before beginning to treat, you risk having some serious neurological damage.
Get a good Pernicious Anemia test early on!
Why Is Pernicious Anemia Misdiagnosed?
- Doctors do not test for B12 deficiency in first place. In most countries, you have to ask your doctor to check your B12 status.
- Before testing for B12 levels, doctors normally look for enlarged red blood cells (macrocytosis). But only ~60% of patients with B12 deficiency will show them. Even neurological symptoms, which indicate an advanced deficiency, may occur in the presence of normal red blood cells. What’s more, supplementing with folic acid (as pregnant women often do) prevents the red blood cells from becoming enlarged. An iron deficiency will also reduce their volume.
- In almost all countries, the current blood level range for determining B12 deficiency are way too low. People experience symptoms at even double those levels! Also, the range is different depending on where you’re from, which means being or not being diagnosed with B12 deficiency depends a lot on your… post code.
- The blood test doesn’t give you the full picture, because it shows both active and inactive forms of B12 in the blood. Also, what happens on the cellular level is far more crucial than how much B12 is circulating in the blood. Sometimes a patient’s levels are above the normal threshold even though he or she is symptomatic.
- The current B12 test, the Combined Binding Luminescence Test, gives false high results in 22-35% of patients, depending on the machine used. It’s not optimal:
It is important to be aware that failure of CBLA assays to detect cobalamin deficiency can occur, especially in cases of pernicious anemia where IF‐blocking antibodies have been implicated in causing assay interference.Laboratory testing for cobalamin deficiency in megaloblastic anemia.
Proper Pernicious Anemia Diagnosis
How to test for Pernicious Anemia then? If you’re diagnosed with a B12 deficiency and want to know if it’s a full-blown Pernicious Anemia — where your body is unable to absorb B12 unless you inject — there are tests to help you.
Which Pernicious Anemia Test to Do?
Which laboratory test is used to diagnose Pernicious Anemia? Remember, the cause of PA is the body producing antibodies that make it impossible to absorb B12. So when you think of getting a Pernicious Anemia blood test, ask specifically for the following two:
Gastric Intrinsic Factor Antibodies (IFA)
The guidelines indicate that all patients suspected of having Pernicious Anemia should go through a test for Intrinsic Factor antibodies, regardless of serum B12 levels. Even in the absence of anemia, patients with low B12 (who don’t have food-bound cobalamin malabsorption or other clear causes) should be tested.
Testing positive for this confirms the diagnosis of Pernicious Anemia. Testing negative doesn’t exclude diagnosis, because the test is not robust enough to detect all cases. Only 40-60% of PA patients test positive for Intrinsic Factor antibodies! This is why guidelines suggest to ignore negative test results, making diagnosis on symptoms alone.
When you take the test, avoid supplementing with B12 for 72 hours. If you had a recent injection, it may seriously compromise the results. And again, the test is not very robust, so if you test negative you may ask to do it several times.
Gastric Parietal Cells Antibodies (PCA, or Anti-GPC)
This Pernicious Anemia diagnostic test is not as specific as the Intrinsic Factor test above, because patients with diabetes and thyroid issues can also have those antibodies. Not only that, but a good chunk of the overall population will test positive for it as well.
If your B12 levels came low, and you test positive for PCA, doctors will often diagnose you with Pernicious Anemia. However, relying on this test to reach Pernicious Anemia diagnosis is not recommended. Further testing for IF antibodies is a smart move.
Important: Before trying to establish a Pernicious Anemia diagnosis, DO NOT supplement with B12. This could seriously skew your test results.
How to Diagnose Pernicious Anemia?
Got the results of your lab tests for Pernicious Anemia? Here’s what to make of them:
Positive for both IFA and PFA? Immunological evidence of Pernicious Anemia. Positive for both is the definitive test for Pernicious Anemia diagnosis.
Negative for both IFA and PFA? No immunological evidence of Pernicious Anemia.
Negative IFA but Positive PFA? 90%+ to have Autoimmune Gastritis, which may end up in Pernicious Anemia one day. Negative IFA does not exclude the possibility of Pernicious Anemia, since only about half of PA patients test positive for this antibody.
Positive IFA but negative PFA? Immunological evidence of Pernicious Anemia if the patient has low hemoglobin macrocytosis (enlarged red blood cells) and low B12 levels. If you’re older than 50, this test alone is usually enough to establish diagnosis. A gastric biopsy may follow to confirm. In the absence of macrocytosis or anemia, repeat in six months with serum gastrin, full blood count and fasting B12 to confirm.
Positive IFA but unknown PFA? Immunological evidence of Pernicious Anemia if the patient is older than 50. Test for PFA to confirm.
Negative IFA but unknown PFA? Test for PFA. About half of all Pernicious Anemia patients test negative for IFA. In contrast, PCA is an excellent indicator of Autoimmune Gastritis, which often ends in Pernicious Anemia with enough time.
Unknown IFA but positive PFA? Again, PFA is seen in more than 90% of patients with Autoimmune Gastritis, which often leads to PA. A small percentage may test positive and never reach the stage of Pernicious Anemia though, so we suggest testing for IFA too.
The Schilling Test For Pernicious Anemia Diagnosis
This test is no longer available. For forty years it was used for Pernicious Anemia diagnosis, but it involved radioactive substances that are no longer in use.
How to Establish a B12 Deficiency In First Place?
The serum blood test for B12 is far from accurate, as it takes into account your levels of inactive B12. A much better test is the holotranscobalamin II (active B12) test, which measures only the active levels in the blood. This will probably replace the current test one day, as sometimes there are significant differences between serum B12 and active B12 levels. Only a few hospitals offer this test though.
Methylmalonic acid (MMA) test is also useful. Increased MMA levels may indicate a B12 deficiency (it is elevated in ~95% of deficient patients), although testing positive could also mean something else, like renal disease, small bowel bacterial overgrowth or haemoconcentration. If plasma levels are exceptionally high (<0.75 µmol/l) though, it is almost certainly a B12 deficiency. It’s a great test, but it’s not common since it uses an expensive gas chromatography mass spectrometry.
Another useful test is the plasma total homocysteine (tHcy) test. It’s not necessarily indicative, because many other things — like low B6 and/or folate, as well as hypothyroidism and renal failure — can elevate homocysteine levels. But it’s a good supplemental test. Another problem is that this test must be carried out within two hours of sampling the blood, which must be kept cool until then.
Other tests are the Mean Corpuscular Hemoglobin (MCH) and the MCHC (Mean Corpuscular Hemoglobin Concentration), which measure the amount of hemoglobin per red blood cell. High levels may indicate a deficiency. The difference is that MCHC takes into account the volume of the cells.
Don’t Put Treatment Away Waiting For Diagnosis
The new guidelines by the British Committee for Standards in Haematology indicate that the most important factor is the clinical picture. So if you show clear Pernicious Anemia symptoms — even if your results look normal or if you are undiagnosed — begin treatment immediately. This is because B12 is a water soluble vitamin, which means any excess is out through the urine. No risk, you can’t overdose!
If you experience symptoms, we recommend asking your doctor for a therapeutic trial of B12 methylcobalamin injections. If they refuse, or if you’d just prefer to take control of your health, you can order from here. Then see if you feel better.
Best of luck with your Pernicious Anemia diagnosis. Don’t panic if you test positive. Luckily, simple and inexpensive B12 shots can take care of you. But don’t wait! When you have Pernicious Anemia, waiting could mean some serious neurological damage.
All the best.