Prothrombin gene variant- clotting

[blissa]

Just wondered if there was anyone around with any experience or knowledge of this?

I was hospitalised with a Pulmonary Embolism nearly 9 months ago. I was on Warfarin for 6 months and came off in July.

The results of my thrombophilia screen has shown that I have PGV. I was negative for Factor V Leiden.

The gp said that I do not need to go back onto warfarin, but if I am pregnant or need to have surgery I will need to temporarily(sp?).

I've tried googling but nothing really helpful has come up, just a lot of case studies.

Hi blissa
PGV is a form of thrombophilia, a condition which means there is a higher level of a clotting factor in your blood than in other people. As you have experienced, this can lead to blood clots. Your risk of developing a blood clot is up to 5 times higher than in someone else your age. However, most people with this condition never develop a clot and your risk of developing another one is probably still quite low. This is why your gp has taken you off the warfarin.

However there are certain circumstances that increase the risk of developing a blood clot in everyone, not just people with thrombophilia. This would include pregnancy and surgery. To put this into context, the risk of an average woman developing a blood clot during pregnancy is about 6 times higher than if they were not pregnant. So this is higher than your risk while not pregnant-if you get me?

So as you can see (if I have explained well enough), during pregnancy, you would be at an increased risk of a clot because of your PGV and a further increased risk because of the pregnancy. It is therefore recommended that you take warfarin to thin your blood during this 'high-risk' period, but only temporarily. As soon as the pregnancy/surgery was over and the increased risk had gone back down to your 'baseline' risk you wouldn't need to take warfarin anymore.

Is that helpful? I was going to write more but don't want to bombard you with too much pointless info!

Hi mooncupnovice- like the name

I had actually gone to the rd about something else and so wasn't ready for this and have since thought of loads of questions!

Thankyou so much for your post, it is very helpful to have it put into English for me! The dr I see gives minimal info, it can be very frustrating.

It is reassuring to be told that even with this condition, the risk of another clot is still quite low. I have been wondering over the past couple of days about aspirin? I am scared of developing another clot, and have recently started councelling to help me through the anxiety I have suffered since Christmas.

I have also been wondering how this has come about. Have I always had this condition, or has it developed recently. I have had 3 children, my youngest is 3, with no problems.

Thankyou for taking the time to post

Sorry- another question!

Is there any connection with PGV and antiphospholipid syndrome? The reason I ask is my sister has this, as well as Lupus SLE.

thanks

Hi again blissa
Firstly I should have put a disclaimer before posting as I am not a doctor, but I have trained in genetics and have a reasonably good understanding of the theory. BUT - If you have been put on any medication by your doctor or he gives you any advice, definitely do as your doctor says rather than going on my advice!

In terms of the anxiety, it is great that your are getting counselling as this can be very helpful. Is it a haemotologist that you are seeing for your PGV? It annoys me that doctors don't take the time to explain things well and listen to your concerns. They really should be willing to address things to put your mind at rest. I dont want to over-reassure you about the risks as I am not 100% sure but it is likely that your risk of developing another clot is low you might be worrying for no reason ( I dont mean NO reason but you know what I mean..? You have every right to worry, I would just prefer it if you didnt have to).

I wouldnt think taking aspirin to prevent clots is advisable but it is definitely worth discussing your concerns with the doctor as there might be other options that would reduce your risk or just clarify the risk for you. I havn't given you risk in percentages as it may be confusing, but I will if you like as I think you would be reassured by some numbers to put it into context?

Oops, I didnt answer half your questions! Yes you have always had this condition, it is something that may not show itself until later in life. But it is something you are born with. It is caused by a 'spelling mistake' in one of your genes. As I said before, the risks of developing a clot will depend on other risk factors on top of your 'genetic' risk if you like. Your blood has always contained more prothrombin than other peoples but this tends not to be a problem unless there is something else that might make your blood clot more easily as well. The fact that you have gone through 3 pregnancies without a clot means that your body was able to deal with this added risk on those occasions.

It is difficult to say why a clot develops. Sometimes you can identify one or more of the 'risk factors' that I keep banging on about (sorry) and sometimes you might not be able to. As far as I understand it, thrombophilias are quite variable. Some people with PGV might develop a clot because they are pregnant. Someone else with PGV might not. But say for example the second person had PGV, were pregnant and went on a long haul flight then they might develop a clot. The risks all add up.

Have you been advised about other situations that would increase your risk?

I dont know if there is any connection with PGV and antiphospholipid syndrome, but perhaps. I will look into it and get back to you. PGV is a genetic condition which can be passed through families. It is possible that other people in your family might not know that they have it. It would be worth asking for a referral to your local genetics service to discuss this. Thats where people like me come in

Hi mooncup

I do intend on going back to see my dr with my questions, but it is great to be able to chat to you and get some info. I really appreciate it.

I won't ask you for percentages as I may or may not be in that percentage iykwim?

I have only seen the gp who runs the INR clinic at our health centre. I do trust him as he's been right every time I've been to him worrying about a DVT!

I've been told I musn't take the pill any more- I've been taking it for 11 years! The dr only mentioned pregnancy and surgery as potential risks. As for the cause of the pe, I did sit for 3 hours on the pc the night before I first felt it. I don't know if that would be the cause?

Ah

I've been wondering whether my dcs will need testing as they get older. A part from my sister, my grandmother suffered a PE but she was in her 80s at the time.

Yep blame mumsnet for keeping you inactive for long periods of time.

Inactivity could be a factor. Other things to bear in mind are the pill as you said, long haul travel, smoking and being overweight. The more of these you can avoid the better. I dont mean dont go on holiday-if you want to fly I think you could ask for warfarin to help short term.

Given your diagnosis and your sisters condition which can also cause clotting problems (I think), seeing someone about the genetics is something you might want to investigate. Speak to the gp and say you would like to be referred to genetics or there might be a haematology clinic locally that also look at family history.

You certainly shouldnt be worrying, it isnt good for you! But finding out as much information as possible can often help put your mind at rest. x

Sorry X posts. It is possible you could have passed it onto your children. In theory they each have a 1 in 2 (or a 50%) risk of inheriting it from you. But again I should emphasise that even if they have, they are still at a very low risk of having any problems. But it might be good to know at some point x

My councellor told me that when we get anxious our body releases anticoags into the blood, so I haven't been doing myself any favours! I am a lot better than I was.

It wasn't mumsnet so I can't blame that. I was downloading music onto dd2s mp3player for her birthday. I am not that great with technology so it took me ages!

Glad to hear that you are feeling a bit better than you were. Try not to let this all worry you- I know its hard having gone through a bad experience. But if you think about pregnant women, they are at a greater risk of developing a clot than you and they probably dont know it! It sounds like you are being monitored now so hopefully they should pick up anything issues early.

I'm off now for the night but I will check back to see how you are doing. Keep me updated. Night night x

Good night and thankyou x

Hi blissa,
I have Factor V Leiden not PGV, but I can speak as someone with a clotting disorder who has had clots, and has since had to negotiate both surgery and pregnancy.

I had a PE some years ago, spent 6 months on warfarin, then came off only to have another PE. My haematologist then put me on lifelong warfarin - this was depressing at the time but, I have since come to realise, not nearly as bad as some other lifelong medications you can be on. Since then I have been fine. Don't know the stats for PGV, but I know that many, many people with FVL never discover their condition, regardless of having children, long haul travel etc.

You're unlikely to need to use warfarin again unless you have another clot and are therefore considered even higher risk for future clots. Again, this has happened to me, and I can say - even this is not as bad as people might think.

One of the limitations of warfarin, though, has come into play for me when having surgery and also when having my DS. Warfarin is relatively slow-acting and it takes a while to get the dose right for each person; it's usually adjusted up and down until it's at the right level. So in contrast to the advice above, you aren't going to be able to use it for flying because it'd take too long for your doctors to get you on the right dose. However, there is an alternative drug, low molecular weight heparin or LMWH (brand names Fragmin or Lovenox) that can be used for certain situations - flying or surgery, as it passes into and out of the system more quickly. (Therefore if after surgery you started bleeding, the situation could be reversed quickly as the LMWH left your system, unlike warfarin which would hang around for ages.) I also went onto LMWH in pregnancy, because warfarin has been linked with serious birth defects and crosses the placenta - in fact, my consultant moved me onto it while TTC to be on the safe side. The downside is that it is given by injection - however, I got used to administering these myself, and again, they are really not as bad as you think. Plus all this is very much a worst case scenario - you have already had 3 pregnancies without problems, and for all I know you may not plan any more anyway!

Most people now seem to be given Fragmin after surgery anyway to prevent blood clots, so this would probably be done for you if needed. Nothing to worry about. I don't know what doctors would do in case of pregnancy with you having had one clot - they might well decide to monitor you closely rather than give you anything; it varies from person to person. But if you developed another clot, you could still be treated with Fragmin during pregnancy.

If it helps, I sailed through my pregnancy with no clotting problems and have since flown to Australia, and have been fine. Happy to try to answer any other questions you have.

Thanks for clarifying the warfarin thing eightieschick, I was unsure about the medication aspect - hence the disclaimer! I knew there were treatments that can be used on a short term basis but have no experience of the details. Thinking about it, warfarin is a nuisance to get right-my nan has been on it for years and the dose has to be constantly adjusted.

It sounds like you have good control over your condition now and I am sure blissa will be reassured to hear from someone who has coped well with a similar condition. It is great to hear your experience, as you say most things aren't as bad as you might think.

Thanks for that EightiesChick, it is good to hear from someone with similar experience.

I only had to inject myself twice with Heparin following my PE, my INR went through the roof so they stopped it and I just carried on with warfarin. My sister has had to inject herself through 2 of her pregnancies.

I am getting my head around it now, and sort of seeing it as a good thing as at least we know I am higher risk, should I ever need surgery.

Thank you both for your help

Hi, I have a question about gene variant for clotting factor 5 and 8. Drs. told me this is inherited from one of my parents. Neither have it. Nor my sibblings. I was on tomaxafin about 10 years ago for stage 1 breast cancer. Used as a preventive measure for it not to reocurr. Six months while on it, I devloped massive and multi DVTS in the legs to which I was rushed to hospital and had a groin filter inserted immediately. Been on warfarin for life now. If I was to get tested for this prothrombin gene variant now, would it show anything since i have been on coumadin for 10 years. I fell the drs blamed it on the factor 5 nd 8 and not the tomaxafin that caused the clots. In my earlier years, I have numberous surgeries in which I would bleed easily and I was given vitamin K shots before surgery. If I had this gene variant, I would have been born with it. It doen't add up bleeding during surgeries and throwing massive clots while on tomaxafin. This was way before I had breast cancer or diagnosed with gene variant.

It seems that I might be a little late to the party here but may be able to help a bit. I am a haemaology lab scientist AND also have Factor V Leiden thrombophilia.

So - like eightieschick, I had to be injected with heparin (clexane) throughout my pg. Warfarin is contraindicated in pregnancy because of the risk to the foetus, but is ok in breastfeeding apparently. I did make sure that I agreed to the vitamin K injection for DS when he was born though, just in case. I have not had any clots, but my Dad has had 2 DVTs, one after surgery, the day after he flew back from Russia (so two risk factors in very short time) and the other some time later but I can't remember what he'd been doing; I think he'd been ill in bed and the inactivity brought it on. He is still not on lifelong warfarin though - although his mother was. But then a paternal aunt of his died of a DVT (PE from it, more likely) 2 days after her hip replacement operation, so we're not sure which side Dad got it from.

However, I always take a shot of heparin before I travel from Australia to the UK and vice versa, just to be on the safe side. I have no wish to get a clot!

Re. the connection with your sister's conditions - SLE is an autoimmune condition, that may or may not be linked to genetic variants but is unlikely to be directly linked to your PGV.
From what I can see, your sister's APS is secondary to her SLE, a common combination, and again is an autoimmune condition where loads of antibodies are made and clog the place up. So again, not directly linked to your PGV, just bloody unlucky.

As you have stated, you now have to come of the combined OC pill, but you may still be able to use the progesterone-only OC pill. If you get pg, you will need to go under a haematology consultant anyway, and have heparin injections. Because you've already had a PE, it's likely that you would need your heparin earlier than me or my sister (we started at 16w) so you would need to go to the doc asap and get a haematology appt sorted asap. Talk to your haematology consultant about pg, if this is a possibility, and see what he/she advises.

Anyway.

babs - assuming that you are talking about Tamoxifen in relation to the breast cancer, it's a hormone-receptor regulator - it is supposed to block oestrogen receptors in the body, thus preventing oestrogen-sensitive cancers from being stimulated. This may or may not affect free oestrogen levels in the blood, I'm not sure - but if it does AND you have a thrombophilic condition, then that explains the tamoxifen's contribution to your DVTs/PEs. Just like the combined OC pill, which also contains a form of oestrogen; and pg, which also increases oestrogen levels.

You cannot be tested for thrombophilia by normal lab clotting tests while on warfarin, as it will interfere with the results. Factor 8 is more usually linked with clotting deficiency, rather than excessive clotting - Factor 5 Leiden is the most common cause for genetic thrombophilia, but there are other factors that can cause it.

I doubt you would get anyone to get gene testing done, given that you are already being medically managed for the situation - you'd probably have to get it done privately, and your use of the word coumadin suggests that you may not be in the UK, so it could be extremely expensive (well, it probably would be in the UK as well, tbf).

HTH.

oh ha ha - a LOT late to the party as far as the OP is concerned!! I didn't realise how old the original thread was. [bublush]

Well, Babs, hope what I've written for you helps anyway![bugrin]

thanks, thumbbunny for the info. One question unaswered: Did the med tomaxifin create the multi DVTs or did I have the gene variant prothrombin being predisposed to clots cause the clots? I think DRs. blamed it on the gene variant. I blame it on the tomaxifin! To cary factor 5, doesn't one of my parents have to have it also.? I believe I never had the clotting disorder because I had several surgeries years ago and never had problems clotting. As a matter of fact, I used to bleed a lot during surgeries. I would get a vitamin K shot before surgery. Doesn't make sense.

The amount you actually bleed isn't that relevant, in all honesty - I bleed a lot whenever I cut myself (haven't had surgery so can't answer that) and it seems to take ages to clot, which also goes against the whole thrombophilia thing - but actually, the thing about thrombophilia is not so much to do with how fast you clot - it's to do with once you start clotting, you don't stop when you should. The control mechanisms that are in place in normal people are defective in thrombophilics.
Clotting happens inside the body as well as when you cut yourself - any blood vessel damage can activate platelets to initiate a clotting cascade. Bruising will initiate the clotting cascade. So the warfarin you takes prevents you from making intravenous clots whenever you damage a blood vessel.

I would say it's likely you have some gene variant causing you to be more sensitive to raised levels of oestrogen, hence your reaction to the tamoxifen - but they can't test you while you're on warfarin/coumadin, so you're not going to find out unless you take the highly risky step of coming off the warfarin for a minimum of 6weeks (6-8w is recommended) to allow your clotting processes to "normalise".

Although most genetic variants are inherited, it is possible that you had a random gene mutation, first in your line, and still have a gene variant giving you thrombophilia.

So - although I thought I had answered it, perhaps too vaguely - I would say that the tamoxifen may have caused the clots, but only because you probably have a form of thrombophilia that made you sensitive to raised levels of oestrogen that may have resulted from your use of the tamoxifen. OR, if it's easier, if you weren't on tamoxifen, you probably wouldn't have had the DVTs.

HTH. Just so you know, the rate of Factor 5 Leiden in the UK population is 1 in 20 (or 5%) of people. That's actually pretty high.