A 25-year-old woman presents to the emergency department having syncopized in the waiting room, where she was triaged with the chief complaint of abdominal pain. Ectopic pregnancy immediately bubbles to the top of your differential diagnosis.
A 25-year-old woman presents to the emergency department having syncopized in the waiting room, where she was triaged with the chief complaint of abdominal pain. Ectopic pregnancy immediately bubbles to the top of your differential diagnosis.
The patient is too dizzy to walk to the bathroom to give you a urine specimen to check a urine pregnancy test. Plus, she admits that she just urinated in the waiting room bathroom a few minutes ago – so no urine now.
Quick Trick
Apply several drops of whole blood (instead of urine) into the pregnancy test cassette. In the photo, the patient was pregnant with a serum beta-HCG level of 250 mIU/mL whose urine and whole blood qualitative tests were both positive.
Did you know that most urine pregnancy test kits are approved for both urine and serum samples? A quick Google search reveals that Accutest, Cardinal Health, ICON, OSOM, and Rapid Response all are approved for both. The question is whether this will work for whole blood. Recall that serum is the extracellular component of whole blood.
One study in the Journal of Emergency Medicine by Dr. Fromm from Maimonides Medical Center looked at exactly this issue(1). Whole blood pregnancy test performed extremely well, especially if positive:
- Sensitivity 95.8%
- Specificity 100%
- Negative predictive value 97.9%
- Positive predictive value 100%
In their study, very low beta-HCG values (<159 mIU/mL) occasionally yielded a false negative for whole blood pregnancy tests. The whole blood testing approach missed a total nine of 425 pregnancies. Interestingly, the urine pregnancy test was also negative in five of those nine and not performed in the other four.
Bottom Line
Believe a positive test. Confirm all tests with a urine qualitative test or quantitative serum beta-HCG.
Tips
Be sure to wait at least 5 minutes when using whole blood in the kit. It sometimes takes a while.
Do not apply additional drops of water or saline to the whole blood sample. This causes unnecessary dilution. Just wait for the blood to osmose across the entire test strip.
References
1. Fromm C, Likourezos A, Haines L, Khan AN, Williams J, Berezow J. Substituting whole blood for urine in a bedside pregnancy test. J Emerg Med. 2012 Sep;43(3):478-82.
2. Habbousche JP, Walker G. Novel use of a urine pregnancy test using whole blood. Am J Emerg Med. 2011 Sep;29(7):840.e3-4.
more on the web
Content for this column taken from
AcademicLifeinEM.com
Michelle Lin, MD
Editor-in-Chief of Academic Life in Emergency Medicine
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Methotrexate for Ectopic Pregnancy
ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479-85.
ECTOPIC PREGNANCY
• 2% of all first-trimester pregnancies and 6% of all pregnancy-related deaths
• Risk factors:
– Prior tubal, pelvic, or abdominal surgery
– Genital infections leading to pelvic inflammatory disease
– Prior ectopic pregnancy
– In utero exposure to diethylstilbestrol (DES)
– History of infertility
– Use of assisted reproductive technologies (in vitro fertilization)
– Tobacco use
METHOTREXATE (MTX
• Dihydrofolate reductase inhibitor – inhibits DNA synthesis, repair, and cell replication
• Overall success rate for treating ectopic pregnancy = 71-94%
• Success rate of single-dose MTX for B-hCG > 5,000 mIU/mL = 85.7%
Side effects: Abdominal pain, nausea/vomiting, stomatitis
Eligibility criteria for MTX in ectopic pregnancy:
• High clinical suspicion or confirmed ectopic pregnancy,
• Hemodynamically stable,
• Unruptured mass,
• Able to comply with close follow-up
• Normal creatinine, liver transaminases, WBC, hematocrit, and platelet counts
Contraindications for MTX in ectopic pregnancy:
• Breastfeeding
• Overt or lab evidence of immunodeficiency
• Alcoholism, alcoholic or chronic liver disease
• Preexisting blood dyscrasias or significant anemia
• Known sensitivity to MTX
• Active pulmonary disease
• Peptic ulcer disease
• Hepatic, renal, or hematologic dysfunction
• Gestational sac > 3.5 cm on U/S (relative contraindication)
• Embryonic cardiac motion on U/S (relative contraindication)
Single-dose regimen:
• MTX 50 mg/m2 IM on Day 1
• Measure B-hCG on Days 4 and 7
• Check for 15% B-hCG decrease between days 4 and 7
• Measure B-hCG weekly until nonpregnant level
• If B-hCG dose not decrease by >15% as expected, re-dose 50 mg/m2 IM and repeat B-hCG on days 4 and 7 after 2nd dose.
Alternative regimens: Two-Dose and Fixed Multidose regimen
(consider for BhCG level > 5,000 mIU/mL)
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>>from the comment stream
Great idea. Could have used this a few years ago when an 18 year old female patient presented unresponsive with a positive FAST exam and hypotensive – we got a urine after cath but, this would have been easier to just use blood sample. She did fine but still less pucker time!
-Brian Rike, DO
… We’re trying to implement Whole-Blood HCG testing as a Department, and are running into the not “FDA-Approved” barrier. Has anybody else discussed with Lab/Pathology departments about this?
-Daniel Lakoff, MD
I have not implemented formally. I am using only in very time-sensitive, active scenarios (hypotensive young woman whose chief complaint is abdominal pain and vag bleeding). We also get a standard urine pregnancy test or serum beta-hcg as a confirmatory test.
-Michelle Lin, MD
Response letter from Dr. Christian Fromm, first author of the cited study, Substituting Whole Blood for Urine in a Bedside Pregnancy Test
To date we have not formalized a process through our laboratory department. Similar to your shop, we use whole blood to make time-sensitive clinical decisions and then try to confirm. But in light of all the recent interest – I have received several inquiries about this matter – I am considering taking this the next step, and I will keep you abreast of any developments.
I should like to add some detail to your discussion of the cases in which there were discrepancies between the urine or whole blood POC tests and the quantitative serum hCG testing. You correctly point out that the whole blood testing missed 9 out of 425 pregnancies and that the urine test was also negative in 5 of those (those 5 hCGs were 5, 16, 18, 47, and 50). Keep in mind that the test is intended to be 100% sensitive only for hCG >25, so that probably explains the false negatives for 3 of them, but is somewhat troubling that both the urine and whole blood missed the hCGs of 47 and 50.
On that point, we do know that false negative urine pregnancy testing can occur in the presence of high levels of hCG variants [please refer to the very interesting recent article by Dr. Richard T. Griffey: “Hook-Like Effect” Causes False-negative Point-of-Care Urine Pregnancy testing in Emergency Patients. J Emerg Med 2013;44(1)155-160], but I’m not sure how likely that is to be the case here with such low hCG values.
As you point out, the urine test was simply not performed due to oversight in 4 of the other discrepant cases in which the whole blood tests were falsely negative, so we will never know if the urine would have missed those too, but I suspect the urine would not have picked those up either because of the low hCG values, which were 6, 9, 12 and 22 (all below the test’s threshold of 25).
There were no discrepant cases in which the whole blood test was negative but the urine test was positive. However, there were two discrepant cases in which the urine tested negative but the whole blood was positive (those hCGs were 83 and 159). So, according to our data, there is a suggestion that the whole blood may actually be more sensitive than urine, but that might require a larger sampling to establish.
16 Comments
Quote:”Keep in mind that the test is intended to be 100% sensitive only for hCG >25, so that probably explains the false negatives for 3 of them, but is somewhat troubling that both the urine and whole blood missed the hCGs of 47 and 50.”
Why do you consider it troubling? IF the patient’s urine is DILUTE, the level of bHCG would likely be below the 25 mIU threshold.
This is yet another reason why the LAB must and DOES maintain authority over all laboratory testing-whether Point of Care – or Laboratory based.
Have you considered that performing the test using whole blood voids the “Waived” testing status, and moves it to High Complexity off label use? By doing so, without approval from your Pathology department, you are putting the entire hospital in jeopordy of losing their CLIA Certificate of Accreditation? Meaning, this one seemingly simple change to the test system could cost you having your entire lab shut down for investigation? As the person in charge of Point of Care Lab for my hospital system, it is things like this that really make me shake my head. Please consult your laboratory before changing the tests you have been approved to use at your institution!
How irresponsible to give these types of directions without laboratory knowledge or approval…not that any lab in the world would approve an alternate sample type for a kit that has not been validated by the manufacturer of the kit!
Can you defend this answer in a court of law since you are using the kit “off label” and contrary to the FDA requirements for the test? Do you have the studies to back up the reliablity and accuracy of this kit with the whole blood?
If so, I hope that they are in the hundreds of samples….
1. Use of a test in a unapproved fashion voids the manufacturer’s instructions, recommendations and cautions.
2. As the test has not been validated for blood in more than just this one study, there is no data on false negative or false positive rates when using a different matrix (blood instead of urine).
3. due to #2 (and as stated in several comments and the letter to the editor) this practice jeopardizes the hospital’s CLIA licence which could have ramifications to the JC certification.
4. Laboratory testing works in a very tightly controlled environment of approved testing controlled exquisitely by the FDA to prevent the mistesting and poor lab practices exemplified by the PAP SMEAR issues of the 80s and before.
5. Your practices should be reviewed by the hospital compliance and risk officers.
David Alter MD
I applaud your desire to take the extra step to take care of your patient in a rapid manner. However, I would suggest that rather than making modifications to the pregnancy test to use whole blood, call your Lab Director (either Administrative or Medical) and ask them to help you get a faster turn around time with serum.
Make the Lab part of your diagnostic team. Inspire them with patient case studies. And I bet your Lab Team will jump through burning hoops of fire to get you the turn around time that you need while still keeping compliant with Federal Laws. After all, we are all here for the same reason – The Patient.
Dr. Lin,
Thank you for this article. I am a paramedic, however, I really enjoy EP Monthly.
There is a substantial benefit and no additional risk of whole blood pregnancy testing in the prehospital setting, if testing were performed at the same time as an IV start or blood glucose measurement.
Dr. Fromm, please consider publication of your study in Prehospital Emergency Care, journal of the National Association of EMS Physicians.
Dr Lin totally rules !
Michelle’s “Homer Simpson” spin on her CME Download fracture lectures is outstanding…
I completely agree with others who have recommended that this type of modification to an FDA-approved test not be implemented without input from the director of the clinical laboratory.
See http://www.pregnancylab.net/2013/09/a-rapid-pregnancy-test-without-using-urine-not-so-fast.html for more information.
I have actually tried this at home due to the fact the we are trying to conceive and I always have dilute urine due to a medication I have to take. I am trained in the medical field so I am aware of how to use sterile technique. There is a study out on this for the person asking about it. The link is http://www.ncbi.nlm.nih.gov/pubmed/21875776 Thank you for such interesting information.
Most of the qualitative hCG kits are manufactured for urine or serum samples (Quickvue, Cardinal Health, etc). However, if we are to change the manufacturer’s instructions for use to include plasma or whole blood testing then we just need to support plasma/whole blood qualitative hCG testing with an internal study. If the study shows statistical significant results then present the finding to the Laboratory pathologist for consult and apporval. An approved study in an institution will comply with most of the Laboratory accreditating agencies. Laboratory science is not a fixed science. We continue to evolve and we should not resist or be afraid of “change”. Let us contemplate a study using whole blood hCG testing and let science evolve.
It’s not fear of “change” or wanting to impede evolution of science in this matter but a very real fear of losing a hospital’s ability to perform and bill for lab testing if the facility loses it’s CLIA license because someone takes a test “Off Label”. There are very strict and extensive guidelines involved in test method validation. Validation (what you are referring to as an internal study) is completely different than a test method verification which alone, is a good deal of work. There are reasons why the tests aren’t approved for whole blood and they come from the manufacturer and government, not the lab. Most manufacturers would most likely be very happy to open their kits up to whole blood but can’t get the approval from FDA for usage with that specimen. Instead of trying to skirt around regulations, cath the patient and do the test. Most qualitative tests for hCG that I am familiar with that use urine or serum take less urine than serum to run and less time to perform (3 vs. 5 minute incubation due to specimen consistency). So spend that time getting a cath specimen if patient is unable to void.
Hmmmm….never knew that was possible. Thanks for sharing this. Anyway, do check this out when you get the time as it has some excellent advise and articles available: https://preganews.com/
If the above scenarios happen we don’t need to cath the patient or send blood to the lab and wait on results. The FDA finally approved a lateral flow blood based pregnancy test- The ADEXUSDx hCG cassette. I wouldn’t risk putting whole blood into a combi (urine/serum) hCG test when none of them on the market are approved for whole blood. I agree with the statements above- you are technically using that off label. Why risk it??
When should we use this blood test? After missing period 2 weeks? 3 weeks? or even 1 month? Thanks for your sharing!
In addition to the above comments, using whole blood invalidates the internal negative control (clear background) so how would you recognize an bad test kit? This kind of wild west lab testing is the entire reason CLIA was enacted. The fact the author specifically states that this hasn’t been validated through the lab should be a giant red flag.
This just in….
I just heard about this practice yesterday. I had a 35 y/o with h/o ectopic and severe and pain. I performed a quick FAST. She had free fluid. I was then told the hcg was negative!! What!? Of course, when I question the nurse, she informs me blood was used. I had a Cath performed and, you guessed it, hcg positive.
Beware! This test is operator dependent. Use only as a last resort. Even then, don’t believe it.