Re: MTHFR for old doctors
From: Terrence.Jones@kp.org
Tue Oct 19 12:55:09 2004
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Where to begin? Think of HCY (homocysteine) as an ingredient in a
soup. It matters what other ingredients are present, and their
concentration, along with the properties of the bowl in which the soup is
placed. Rather than predict thrombosis risk on the basis of a single
ingredient, a better measure would be the viscoelastic properties of the
final product and how it interacts with endothelium (normal or damaged).
Someday... Maybe, in the meantime, SELDI + Mass Spec + a little data
mining = informative correlation coefficients? Waiting is...
Certainly has been some recent interest in folate supplementation
(co-enzyme for MTHFR) to reduce CVA. B-6 and B-12 are probably more impt
in the other two cysteine pathways.
You asked about Menostar a few weeks ago (ultra low dose ERT
patch) - check out O/G 104:443-51 (Ettinger). NA7, 0.014 mg/D, serum
increase from 4.8 to 8.6 pcg/ml. Hip BMD increase 0.4%, vs decrease of
0.8% in placebo. 1 Case hyperpl in Rx group; none in placebo ("not sig").
The oral ERT supps raise CRP (C-reactive protein) from first pass hepatic
FX, this is reduced with transdermal. The pro-inflam cytokine (CRP) may
aggravate pre-existing CAD (too much salt in the soup!). tj
garrys@mindspring.com (Garry E. Siegel, M.D.)
Sent by: ob-gyn-l@obgyn.net
10/18/2004 06:19 PM
Please respond to ob-gyn-l
To: Multiple recipients of list OB-GYN-L <ob-gyn-l@dns.obgyn.net>
cc:
Subject: Re: MTHFR for old doctors
I'll look up the articles.
Thanks, Art and Ron, and I do expect TJ to explain it, but I hope that I
can understand what he says.
Garry
At Mon, 18 Oct 2004, ainsron wrote:
>
>I believe this came from an article in Contemporary Ob/Gyn:
>
>The MTHFR mutation is an autosomal recessive trait with a thrombotic
effect
>which is generally low during pregnancy or in estrogen-replete women,
>dependent on level of homocysteine. This thrombophilia results in
increased
>amounts of the essential amino acid homocysteine build up in the plasma.
The
>elevated levels have a toxic effect on the endothelium, leading to clot
>formation. Approximately 11% of Caucasians are homozygous for the most
>common cause of homocysteinemia, a mutation in methylenetetrahydrofolate
>reductase, abbreviated MTHFR. (Patients call this the "Monday, Thursday,
>Friday" disease.) Because estrogen decreases homocysteine levels in the
>serum, this disease rarely causes DVT in pregnancy.
>Nonpregnant patients with mild hyperhomocysteinemia may take oral
>contraceptives or use hormone replacement therapy. However, the MTHFR
>mutation may induce thrombosis postpartum. Hyperhomocysteinemia, unlike
the
>other inherited thrombophilias, may be associated with recurrent
embryonic
>loss, as well as fetal loss.
>Homocysteinemia is both embryotoxic and mutagenic. As many as 50% of open
>neural tube defects may be associated with the MTHFR mutation. Cardiac
>mutations may also be associated with elevated homocysteine levels.
>Moreover, the MTHFR mutation has been associated with preeclampsia,
growth
>restriction, and abruption.
>Women with MTHFR mutation, are given 4 mg of folic acid, in addition to
>their prenatal vitamins, 250 µg of B12 and 25 mg of B6. Check a fasting
>homocysteine level 2 weeks later and, if that is abnormal, we increase
the
>folic acid to 5 mg a day and the B6 up to 100 mg. Women who fit this
profile
>do not need heparin therapy.
>With respect to changes in pregnancy management for women with
>thrombophilia, consider obtaining an ultrasound at 30 to 32 weeks to look
at
>fetal growth. Doppler studies are not helpful in these patients in the
>absence of growth restriction. Unexplained elevated maternal serum
>alpha-fetoprotein levels suggest placental disease.
>
>Ronald E. Ainsworth
>
>-----Original Message-----
>From: ob-gyn-l@obgyn.net [mailto:ob-gyn-l@obgyn.net] On Behalf Of Garry
E.
>Siegel, M.D.
>Sent: Monday, October 18, 2004 3:28 PM
>To: Multiple recipients of list OB-GYN-L
>Subject: OB: MTHFR for old doctors
>
>40 YO P1314 at 10 weeks, with no personal history of thromboembolism:
>
>Ob #1 1987, different hubby--spont PTL after uncomp preg, delivered at
>32 weeks.
>
>Ob #2, 1996, this hubby--35 week severe PIH due to IUGR, delivered due
>to same.
>
>Ob #3, 1999, 38 weeks, mild PIH, induced and delivered.
>
>Ob #4, 2001, 36+6, spont labor and delivery, no PIH.
>
>Ob #5, 2004, surprise(!), normal nuchal translucency/blood at 13 weeks,
>demise at 18 weeks. No studies done as they weren't having more
>children.
>
>Thus, given the above, did testing for the thrombophilias:
>
>Results negative for Lupus anti-coagulant, cardiolipin antibody, Factor
>V Leiden, ATT III, Protein S and C, yaday.
>
>MTHFR heterozygous positive, and MFM says no problem, but to test
>fasting homocysteine, which is being done.
>
>Here's my real question:
>
>I can't really find the basic science on this in anything I have. I've
>found a 1997 reference, and have ordered it. Does anyone have any
>articles for old doctors about thromobophilias in general?
>
>Thanks,
>
>Garry
>
>--
>Garry E. Siegel, M.D.
>Private Practice
>Roswell, GA
>
--
Garry E. Siegel, M.D.
Private Practice
Roswell, GA
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<br><font size=2 face="sans-serif"> Where to begin? Think of HCY (homocysteine) as an ingredient in a soup. It matters what other ingredients are present, and their concentration, along with the properties of the bowl in which the soup is placed. Rather than predict thrombosis risk on the basis of a single ingredient, a better measure would be the viscoelastic properties of the final product and how it interacts with endothelium (normal or damaged). Someday... Maybe, in the meantime, SELDI + Mass Spec + a little data mining = informative correlation coefficients? Waiting is... </font>
<br>
<br><font size=2 face="sans-serif"> Certainly has been some recent interest in folate supplementation (co-enzyme for MTHFR) to reduce CVA. B-6 and B-12 are probably more impt in the other two cysteine pathways.</font>
<br>
<br><font size=2 face="sans-serif"> You asked about Menostar a few weeks ago (ultra low dose ERT patch) - check out O/G 104:443-51 (Ettinger). NA7, 0.014 mg/D, serum increase from 4.8 to 8.6 pcg/ml. Hip BMD increase 0.4%, vs decrease of 0.8% in placebo. 1 Case hyperpl in Rx group; none in placebo ("not sig"). The oral ERT supps raise CRP (C-reactive protein) from first pass hepatic FX, this is reduced with transdermal. The pro-inflam cytokine (CRP) may aggravate pre-existing CAD (too much salt in the soup!). tj</font>
<br>
<table width0%>
<tr valign=top>
<td>
<td><font size=1 face="sans-serif"><b>garrys@mindspring.com (Garry E. Siegel, M.D.)</b></font>
<br><font size=1 face="sans-serif">Sent by: ob-gyn-l@obgyn.net</font>
<p><font size=1 face="sans-serif">10/18/2004 06:19 PM</font>
<br><font size=1 face="sans-serif">Please respond to ob-gyn-l</font>
<br>
<td><font size=1 face="Arial"> </font>
<br><font size=1 face="sans-serif"> To: Multiple recipients of list OB-GYN-L <ob-gyn-l@dns.obgyn.net></font>
<br><font size=1 face="sans-serif"> cc: </font>
<br><font size=1 face="sans-serif"> Subject: Re: MTHFR for old doctors</font></table>
<br>
<br><font size=2 face="Courier New">I'll look up the articles.<br>
<br>
Thanks, Art and Ron, and I do expect TJ to explain it, but I hope that I<br>
can understand what he says.<br>
<br>
Garry<br>
<br>
At Mon, 18 Oct 2004, ainsron wrote:<br>
><br>
>I believe this came from an article in Contemporary Ob/Gyn:<br>
><br>
>The MTHFR mutation is an autosomal recessive trait with a thrombotic effect<br>
>which is generally low during pregnancy or in estrogen-replete women,<br>
>dependent on level of homocysteine. This thrombophilia results in increased<br>
>amounts of the essential amino acid homocysteine build up in the plasma. The<br>
>elevated levels have a toxic effect on the endothelium, leading to clot<br>
>formation. Approximately 11% of Caucasians are homozygous for the most<br>
>common cause of homocysteinemia, a mutation in methylenetetrahydrofolate<br>
>reductase, abbreviated MTHFR. (Patients call this the "Monday, Thursday,<br>
>Friday" disease.) Because estrogen decreases homocysteine levels in the<br>
>serum, this disease rarely causes DVT in pregnancy.<br>
>Nonpregnant patients with mild hyperhomocysteinemia may take oral<br>
>contraceptives or use hormone replacement therapy. However, the MTHFR<br>
>mutation may induce thrombosis postpartum. Hyperhomocysteinemia, unlike the<br>
>other inherited thrombophilias, may be associated with recurrent embryonic<br>
>loss, as well as fetal loss.<br>
>Homocysteinemia is both embryotoxic and mutagenic. As many as 50% of open<br>
>neural tube defects may be associated with the MTHFR mutation. Cardiac<br>
>mutations may also be associated with elevated homocysteine levels.<br>
>Moreover, the MTHFR mutation has been associated with preeclampsia, growth<br>
>restriction, and abruption.<br>
>Women with MTHFR mutation, are given 4 mg of folic acid, in addition to<br>
>their prenatal vitamins, 250 µg of B12 and 25 mg of B6. Check a fasting<br>
>homocysteine level 2 weeks later and, if that is abnormal, we increase the<br>
>folic acid to 5 mg a day and the B6 up to 100 mg. Women who fit this profile<br>
>do not need heparin therapy.<br>
>With respect to changes in pregnancy management for women with<br>
>thrombophilia, consider obtaining an ultrasound at 30 to 32 weeks to look at<br>
>fetal growth. Doppler studies are not helpful in these patients in the<br>
>absence of growth restriction. Unexplained elevated maternal serum<br>
>alpha-fetoprotein levels suggest placental disease.<br>
><br>
>Ronald E. Ainsworth<br>
><br>
>-----Original Message-----<br>
>From: ob-gyn-l@obgyn.net [mailto:ob-gyn-l@obgyn.net] On Behalf Of Garry E.<br>
>Siegel, M.D.<br>
>Sent: Monday, October 18, 2004 3:28 PM<br>
>To: Multiple recipients of list OB-GYN-L<br>
>Subject: OB: MTHFR for old doctors<br>
><br>
>40 YO P1314 at 10 weeks, with no personal history of thromboembolism:<br>
><br>
>Ob #1 1987, different hubby--spont PTL after uncomp preg, delivered at<br>
>32 weeks.<br>
><br>
>Ob #2, 1996, this hubby--35 week severe PIH due to IUGR, delivered due<br>
>to same.<br>
><br>
>Ob #3, 1999, 38 weeks, mild PIH, induced and delivered.<br>
><br>
>Ob #4, 2001, 36+6, spont labor and delivery, no PIH.<br>
><br>
>Ob #5, 2004, surprise(!), normal nuchal translucency/blood at 13 weeks,<br>
>demise at 18 weeks. No studies done as they weren't having more<br>
>children.<br>
><br>
>Thus, given the above, did testing for the thrombophilias:<br>
><br>
>Results negative for Lupus anti-coagulant, cardiolipin antibody, Factor<br>
>V Leiden, ATT III, Protein S and C, yaday.<br>
><br>
>MTHFR heterozygous positive, and MFM says no problem, but to test<br>
>fasting homocysteine, which is being done.<br>
><br>
>Here's my real question:<br>
><br>
>I can't really find the basic science on this in anything I have. I've<br>
>found a 1997 reference, and have ordered it. Does anyone have any<br>
>articles for old doctors about thromobophilias in general?<br>
><br>
>Thanks,<br>
><br>
>Garry<br>
><br>
>--<br>
>Garry E. Siegel, M.D.<br>
>Private Practice<br>
>Roswell, GA<br>
><br>
<br>
--<br>
Garry E. Siegel, M.D.<br>
Private Practice<br>
Roswell, GA<br>
</font>
<br>
