Eureka! Found the genes! Heterozygous on FVL + Heterozygous on FV HR2 = pseudohomozygous

Last year, after decades of health issues and no answers, I sent $99 to 23andme and I did a genetic spit test and sent it back to them in the mail. From that DNA, I learned I was heterozygous for Factor V Leiden (FVL) (rs6025). I brought that result back to my doctors who tested me at a medical lab and said "yes you are".

I just checked my gene sequence on 23andme for the Factor V HR2 allele (rs1800595) and I am heterozygous for that also. I believe about 10% of the population has this allele (so it's not that unusual). Anyone with Factor V Leiden should be tested for it.

Being heterozygous for FVL and also heterozygous for Factor V HR2 automatically makes me pseudohomogzygous for FVL (link to study:

This result takes my already higher risk of thrombosis due to FVL (one gene) and multiplies that risk by 3 or 4 times. (link:

More info on the gene combination: bloodjournal.hematologylibr...

I will of course have the Factor V HR2 allele verified with my doctor through a medical lab. My question that I would like to put to all my doctors (but I probably won't) is "Why did I have to find Factor V on my own last year?" and "Why did I have find Factor V HR2 on my own this year?" Why aren't I being taken seriously and given the tests that these specialists should know to give me given my symptoms and history? Do doctors need to be better educated on these genes? Is it our responsibility to then go back to our our doctors and educate them?

I occasionally feel like I am paying the big dollars to the doctors in order for me to educate them. It's great to have answers, but it would have been nice to have a doctor let me know about it instead of it being the other way around.

My appointment with the APS specialist comes up in a few days. I am hoping he understands the above. Since his paperwork asks about many genes, but not the Factor V HR2, I am afraid that I'll have to pull out my copies of two dozen studies to educate him. Better to be prepared.

21 Replies

  • Well as one Miss Marple to another, I can only honestly say most of us are having to do this, it is also the same with Thyroid disease, due to faulty testing, yet it is so very prevalent especially around autoimmune disease. I partly volunteered to do this on here due to the amount of reading I had done... over the years on behalf of myself, siblings, late parents and my children. Also I wanted to put my energy to good use, as I had been quite cross due to misdiagnosis and at times some non listening medical ears, which thankfully has changed now.

    When you hand it over, do so in a way for them to read later.. that way the penny is more likely to drop more efficiently. MaryF

  • Great idea! I hadn't thought of that. Yes, leaving them reading will help. Thanks Mary! I will visit the copier.

  • I'm glad you have found some answers.

    Sadly it is mostly left to us to find our own diagnosis and hand it on a plate to the doctors.

    A prime example from today ...With all the blood tests I've had over the last few years no-one bothered to check my folate and it was only because I requested various vitamin tests be done and he threw in a folate test to discover I am folate deficient. ...and it was only because I had the results sent to me and prompted him about the folate results that he actually told me about it. And he is my reliable doctor ...hmmm

  • I totally agree with MaryF.

    Take it easy and ask the questions that are most important (you have written them down).

    Perhaps there are not so many APS-specialists around and you do not know how this professor reacts on a patient that throws irrelevant questions on him (irrelevant to him). You certainly do not have more than half an hour or up to one hour with him so do not waste that time. Few doctors are like professor Hughes. Doctors hate to be educated!

    Give him some papers to read later on.

    Good luck from one patient to another.


  • Please explain to me what Factor V HR2 allele is. I have Factor V Leiden Heterozygous, and APS. I went on the internet to find out what HR2 is, but no luck.

  • What is pseudo-homozygous Factor V Leiden and why is it important? Great question!

    Being heterozygous Factor V Leiden means that only one parent had the mutation and therefore you only have one copy of it (not two). Being homozygous Factor V Leiden means that both parents gave you a copy so you have two. Being pseudo-homozygous Factor V Leiden is where you are heterozygous Factor V Leiden and you also have one copy (heterozygous) of Factor V HR2 (also called R2 by some labs).

    Factor V HR2 is a null factor. That means if you have two copies of Factor V HR2 then you aren’t making any Factor V. People who are homozygous Factor V HR2 have a bleeding disorder because they aren’t producing the clots necessary to stop bleeds. However, people with one null factor for Factor V (so not producing any Factor V per one gene) and who are heterozygote Factor V Leiden on the other gene – these people produce half the Factor V and it’s only the bad (mutated kind). Therefore people with this combination have their blood act as if they are homozygous Factor V Leiden. That’s why it’s called pseudo-homozygous Factor V Leiden.

    Being pseudo-homozygous Factor V Leiden is important because it comes significantly more clotting risks. In fact, there have been a few studies that found that pseudo-homozygous FVL caused a more pronounced hypercoaguable state than homozygotes FVL. Per this study, Chapter 6 (begins page 111):

    “SUMMARY. The factor V Leiden (FVL) mutation causes activated protein C (APC) resistance and increases the risk of venous thrombosis. FVL pseudo-homozygotes are heterozygotes that carry a null mutation on the counterpart FV allele. Like homozygotes, they have only FVL in plasma, but their partial FV deficiency also predicts low plasma levels of tissue factor pathway inhibitor (TFPI), which may exacerbate their hypercoaguable state. We compared 9 FVL pseudo-homozygotes and 18 homozygotes. Pseudo-homozygotes had lower TPFI levels, higher thrombin generation and higher APC resistance than homozygotes, indicating a more pronounced hypercoagulable state and possibly a higher thrombosis risk than in homozygotes.”


    “The clinical implication of this finding is that protocols for VTE prohylaxis and treatment in FV Leiden pseudo-homozygotes should be similar to those used in FV Leiden homozygotes (or double heterozygotes for the FV Leiden and prothrombin G20210A mutations) according to the current antithrombotic guidelines.”

    Study link:

    I am finding that the really great hematologists here in the United States are completely unaware of pseudo-homozygous FVL. It’s not even on their screen. At first, I was bugged that my doctors were the ones oblivious to it – but now I realize that none of them know about it. I haven’t run into any yet that know about it.

    That is just scary when up to 10% of a population can carry the null FVL gene. So imagine that you are a hematologist and see many FVL heterozygotes. And now imagine that 10% (or more since the ones coming into you office are the ones not feeling good and more likely to have risky gene combinations) of your FVL heterozygote patients also have that null FVL gene. This means a lot of people who are not feeling well are not being treated with prophylaxis anticoagulant therapy (as mentioned in the study above).

    I am happy to report that the doctors I have met with are very interested in learning more. I am bringing to my appointments copies of the studies on pseudo-homozygous FVL to leave with them. Today I had a doctor ask if he could copy some of my additional studies I had with me today for fun reading tonight. :-) I am also providing them with the copies of LabCorp and Quest Diagnostics lab tests numbers that correspond to testing for this. It just makes their lives easier if they decide to test future patients for the HR2 mutation.

    Here are the two labs from LabCorp that test for R2:!ut/...!ut/...

    Here are the labs from Quest Diagnostics for R2:

  • Hi, How did the meeting with the APS-doctor go? I have been thinking of you. Were you satisfied with him?

    Best wishes from Kerstin in Stockholm

  • Me, too!

  • Yes, my appointment was yesterday and it went very well. I was very impressed with Dr. Doruk Erkan, MD. Please add him to the list of Antphospholipid specialists. He is Associate Professor of Medicine at Weill Medical College Cornell University..... and practices at the Barbara Volker Center for Women and Rheumatic Disease. 535 East 70th street, New York City, NY.

    He took a full hour and 15 minutes with me. He looked through all my records, told me about his practice, and listened to all my concerns and questions. I give him 5 stars. My assessment of him -- very intelligent, compassionate, no ego issues to get in the way. He looked at my test results and found my numbers to be so low that he wouldn't consider it antiphospholipid syndrome. That doesn't mean he wasn't concerned and isn't giving up.

    He was very interested in the pseudo-homozygous factor V Leiden. Since my original test on the heterozygote FV HR2 was just through 23andme, he did a blood test to confirm at a medical lab (results should be in next week). He also told me for my very low vitamin D to take one 50,000 IU Vitamin D3 (Replesta brand) once a week and 2000 IU vitamin D on the other days. He told me to do that for 12 weeks. I have heard a lot of people talk about the high dose VItamin D3 on this site. I hadn't realized it was over the counter here in the United States and that I could get it at a pharmacy without a prescription or online at I believe the coupon code HEALTH gives a 10% discount. Dr. Erkan said that with his patients, he sees a lot of improvement in quality of life by increasing their vitamin D when low on blood tests.

    He did many additional blood tests. He is rerunning the antiphospholipid panel and also running a homocysteine test.

    He was surprised that nobody had tried coumadin (Warfarin) on me in the past to see if it helped my symptoms (despite no clots on medical tests). He didn't see any reason why even my general practicing doctor couldn't prescribe a trial period of 3 months for it. I want to be with a specialist for my specific psuedo-homozygous FVL before I start with medicines. So I may wait to see how long I get into see the specialist. He is going to call me next week to discuss the results.

    He suggested that if it is confirmed that I am pseudo-homozygous Factor V, that my next stop should be with the hematologist that he finds excellent and who specializes in thrombosis. Her name is Maria DeSancho in NYC. Here is a link about her.

    While we didn't talk seronegative APS, I felt like he looks to the tests and antiphospholipid and rechecks the info and then tries to see if there are alternative reasons (lyme disease, genetic thrombosis, etc...) for the similar symptoms to APS. He had a ton of paperwork and handouts on APS. While I may not be specifically APS, he is the first doctor who I really felt listened to me, is following up with me, and is going to send me onto someone who specializes in what he believes I have. In addition, I was given a first appointment with him as a new patient within two weeks of calling his office. That is unheard of with the really good doctors.

    I am absolutely impressed. 5 stars. Progress. I am thrilled! :-)

  • Hi

    I just read your post about seeing Dr. Erkan. I have an appointment to see him next Wed. and I was happy to read that you were so impressed with him. I was diagnosed with APS last fall (no clots) , after seeing a dermatologist for livedo reticularus. I suffer from chronic migraines, have had numerous false positive VDRL tests and high titer levels for anticardiolipin, beta-2 glycoprotein and lupus anticoagulant. I was put on a daily dose of 325mg of aspirin and that is about it. I am hoping to get a little more clarity on the condition especially as it relates to the chronic migraines, as that is my greatest disability.

    Thank you for sharing!

  • Hi MigraineMom!

    That's wonderful that you are able to go and see Dr. Erkan. Please let me know how it goes. Remember to bring copies of all your tests. If you are like me (brain fog), you may also want to write out all your questions ahead of time.

    All the best!

  • Thank you ! I am in the process of getting all of my records, questions and notes together in anticipation of my appointment. I will let you know how it goes..

    Thanks again for responding...

  • Great! I hear you were satisfied with him. I wonder what he believes you have as you have so many APS-symptoms.

    Good luck from Kerstin

  • My LabCorp test came in positive for Factor V R2. I am confirmed pseudo-homozygous FVL. In LabCorp's statement with the results it states that my heterozygote FVL plus heterozygote FV R2 multiples my already higher risk of venous thrombosis due to being heterozygote FVL by 3 to 4 times. That's huge and explains a lot.

    Side note, I have been having stomach issues due to taking the low dose daily aspirin. I found the prior thread on aspirin upsetting people's stomachs and the repeated suggestion to try Clopidogrel (Plavix). I'll be at my pharmacy later today. Thanks for all the great information on this site. Hugs!

  • Have you tried the enteric coated aspirin? Much easier on the stomach.

  • Good morning Ann!

    Yes, I am trying the enteric coated aspirins for a few days while waiting on my Clopidogrel prescription. It does seem to have made a difference.

    But I'm keeping my options open. I have found a few studies that question enteric coated aspirin's impact on stomach bleeding and also wonder if it decreases the amount of aspirin that gets into the system. Here is a link to an article on the subject by University of California, Berkley Wellness. In the article, they state there is really no answer since there aren't enough studies and there are so many different impacting factors. Therefore, I'm going to listen to what my stomach says and what your experience has been. :-)

    Thanks as always and have a great day!

  • When my neurologist first suggested aspirin, I started taking one 325 aspirin. I took that dose because it was so much cheaper than "cardiac" dosages. I was taking it in the evening with my largest meal to avoid stomach distress. I had been having a constant "sinus" headache which ibuprofen or even Tylenol with codeine didn't help that much. After I took the aspirin the "sinus" headache would improve dramatically. Since the headache started as soon as I woke up I thought I'd try and aspirin with breakfast, too. And now I have pretty decent pain relief from the headache all day. But since I also have joint pain, I started taking two aspirin at a time, twice a day. My rheumatologist also gave me meloxicam at night. The aspirin did start to bother my stomach, and I bought the enteric coated aspirin. Since I get instant bodily feedback by the effect on my headache, using two enteric coated aspirin didn't work as well. So now I'm taking one plain aspirin and one enteric aspirin in the morning with breakfast which will help my headache go away, and in the evening I take two enteric aspirin. This is probably TMI, but I think the enteric aspirin gets into your system, but not a quickly as plain aspirin. I also am more comfortable taking old drugs than new drugs, since the side effects are known, and we are guinea pigs for new drugs. But if it's bugging your stomach, it's bugging your stomach. Since one small dose is usually the recommended dose, if you are worried about whether or not you are getting enough, you could just double it. I think you would be pretty much sure, then. But are you seeing any reaction with your neurological symptoms? Before, I started aspirin I would have been hard pressed to write this paragraph. After I started with the aspirin I was able to write more smoothly, at least some of the time. Or maybe I just think I can.

  • i have learnt and tried a low-dose Aspirin of 75 mg for APS. It worked well for several years. Then I started having more severe symptoms and we tried the double dose. That did not do any difference to APS but I had some stomach-problems. With warfarin I am fine.

    So I wonder if the double dose has any effect at all on the APS-symtpoms. Pain is something else.

    It says you shall take a low dose Aspirin.

    Kerstin in Stockholm

  • You may be right about that, but I'm also taking it for joint pain. The sinus pain I don't really understand, but for some reason taking aspirin twice a day works better than anything else I've tried, including ibuprofen and Tylenol with codeine--or taking aspirin just once a day.

  • It's just like the movies... If it less than what is expected you still have to pay for it or else find another and move on..Maybe you need to move on. Although it doesn't hurt to educate them, as the more who are informed, the safer we should be, tongue in cheek..ha ha. Print and give out copies of the APS fact sheets to them . You may want to charge them for the tutorials ha ha. It's late and I'm getting stupid, my apologies🤔

  • You can find the fact sheets on the Hughe's syndrome website listed above right side. Good luck!

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