Category Archives: Amniocentesis

Amniocentesis

Discrepancy in Lamellar Body Counts (LBC) between the Sysmex XE-2100 and Sysmex XT-2000i instruments


Recently, we blogged about a paper by Kyle & Lawrence that demonstrated poor precision of the lamellar body counts (LBC) using the Coulter Unicel DxH 800 instrument. Now we want to make you aware of a study by Beaudoin and others that demonstrates a bias in LBCs between the Sysmex XE-2100 and Sysmex XT-2000i instruments.

Previous reports have demonstrated excellent concordance between the LBC when performed on Sysmex XE-2100 and the Coulter-brand instruments. However the Beaudoin  laboratory recently noticed a positive bias in LBC results using the Sysmex XT-2000i. Therefore, they conducted a study to compared LBC results in 52 specimens using two Sysmex models (Sysmex XE-2100 and Sysmex XT-2000i), with those of the Coulter LH-750.

The authors demonstrated a very small negative bias (mean = -8%) between the Coulter LH-750 and the Sysmex XE-2100. However, the Sysmex XT-2000i had significantly higher results than the Coulter LH-750 (mean bias = 56%). Interestingly, despite the difference in LBCs, similar results were obtained on all 3 instruments when platelets were counted using Sysmex e-CheckTM control material or whole blood specimens.

Using Deming regression to extrapolate the appropriate cutoff, the authors calculated that the medical decision limit for the Sysmex XT-2000i is closer to 77,000 counts/µL, which is 54% higher than the 50,000 counts/µL recommended for the Coulter LH-750. The reason for this difference is not understood, but is likely related to the different principles to count lamellar bodies on each instrument. Although, all three of the analyzers in this study use impedance principles to count platelets, each analyzer counts slightly differently. The authors speculate that the difference may be due to the fluid used for the hydrodynamic focusing of the samples.   

This study once again highlights the need for manufacturer- as well as model-specific LBC clinical decision limits. Laboratories performing LBCs on hematology analyzers should be aware of this important analytical variable. Individual laboratory LBC cutoffs need to be established even when using the analyzers from the same manufacturer if the models are different.

Screening or diagnostic test. What is the difference?


Today was an interesting day at work.  A genetic counselor I work with emailed me that a pregnant patient wanted to have "every single Down syndrome screening test that was available."  While this was problematic in and of itself (more about that later), this patient also planned to have an amniocentsis regardless of the results of the screening test.

Do you see a problem with this line of thinking?  If not, read on.

Let's start with what a screening test is.  I've written about this before here, but to recap: a screening test is NOT the same as a diagnostic test.  A test that screens for Down syndrome doesn’t identify if a woman is pregnant with a baby that has Down syndrome; it identifies women who are pregnant with babies that are at increased risk of having Down syndrome.  In other words, the screening test puts tested women into one of two camps: those without increased risk and those with incrased risk.  Women who screen positive and who are at increased risk are offered a diagnostic test that can confirm if their baby does or does not have Down syndrome.  A screening test cannot do that.

The diagnostic test for Down syndrome is determining the karyotype of the fetus in order to identify how many copies of chromosome 21 have been inherited (unaffected fetuses have 2 copies; affected fetuses have 3 copies).

The results of a Down syndrome screening test are used to identify women who should be offered diagnostic testing (karyotype).  Women who have a positive screening test result are offered amniocentesis in order to obtain  the amniotic fluid required for karyotyping the fetus.  However, because amniocentesis is an invasive procedure, there is a small risk of miscarriage (usually less than 0.5 percent).

The problematic request of the patient to have more than one Down syndrome screening test should now be apparent for two reasons:

  1. Her desire to have every available screening test is illogical if she has already made up her mind to have an amniocentesis and diagnostic testing.  The fetal karyotype is THE definitive (i.e. diagnostic) test and so screening for a disorder makes no medical or economic sense because, regadless of the results, the diagnostic test will still be performed.
  2. Requesting all available screening tests is a complete waste of health care resources.  Granted, the number of Down syndrome screening tests available is a source of much confusion for both physicians and patients.  That said, patients (with help from their doctors) should choose the screening test that is best for them.  Choosing multiple screening tests is not a wise idea.  Consider what might be done if the results of these tests don't agree with each other.

Consumers of health care often (mistakenly) believe that more testing is better.  Few take the time to consider that tests may have downstream consequences that they might not be prepared for.  In this case, the patient had already decided to have the "best" test.  That is her choice and one that I support.  What I don't support is the wasted time, money, and effort required to perform tests that are, in this specific situation, meaningless.

New blood test for Down syndrome screening


This is impressive!  A study reported yesterday in the British Medical Journal describes a new blood test that could vastly decrease the number of invasive procedures that are currently used to confirm if a fetus has Down syndrome.

Current blood tests used for Down syndrome screening can identify up to 90-95% of Down syndrome pregnancies but about 5% of normal fetuses are incorrectly identified as having Down syndrome.  That means that lots of women have follow-up tests, like amniocentesis, to definitively determine if their baby is affected.  That's a problem because amniocentesis is an invasive procedure that can lead to the loss of the pregnancy.  Current estimates put the risk of fetal loss due to amniocentesis at about 1 out of 300. 

914335_85510317 This new blood test measures the amount of DNA from chromosome 21 that is present in the mother's blood.  Down syndrome is caused by having an extra copy of chromosome 21.  We know that a pregnant woman's blood contains small amounts of her baby's DNA but that amount is very
low compared to the amount of her own DNA in her blood.  Using a technique called massively parallel sequencing, this test looks for increased amounts of pieces of chromosome 21 in the mother's blood.  In a Down syndrome pregnancy, the mother's blood will have more pieces of chromosome 21 because the fetus has an extra copy of that chromosome.

The study used blood collected from 753 women who were at high-risk of having a baby with Down syndrome.  86 of these pregnancies were carrying a fetus with Down syndrome and the test was able to correctly identify 100% of them.  While that alone is impressive, even more exciting is that only 2.1% of the unaffected fetuses were incorrectly identified as having Down syndrome.  Stated another way, in 98% of the cases Down syndrome could be ruled-out sparing the need for invasive follow-up testing.  Like some of the existing blood tests used to screen for Down syndrome, this new test can be performed in the first trimester of pregnancy.

Although the test is not yet available, there is a company that is working on making it available soon.