Re: Factor V Leiden and OCs
From: ainsron@msn.com
Mon Nov 6 10:06:59 2000
Thanks for the information.
>Found this on --Syllabus Seminar at San Juan -Feb 2000 Hope it comes out
>Ok Scan-OCR-Word-copy-paste
>
>ADVANCES IN MOLECULAR GENETICS THAT IMPACT OB/GYN PRACTICE
>Aubrey Milunsky, MB.B.Ch.,D.Sc.,F.R.C.P.,F.A.C.M.G.,D.C.H.
>SPECIFIC GENES AND THEIR MUTATIONS AS RISK FACTORS FOR VENOUS OR
>ARTERIAL THROMBOSIS
>Gene mutations that cause clots to form in veins or arteries or
>predispose individuals to such complications are responsible for a whole
>range of such disorders called the inherited thrombophilias. Genetic
>disorders involving platelets, protein C and S and fibrinogen,
>homocysteine as well as genes encoding antithrombin may all result in
>vascular thrombosis. The prevalence of defects in most of these factors
>appears to be relatively low, exceptions being venous thombosis due to
>mutations in the Factor V Leiden gene and the specific mutation (20210A)
>in the prothrombin gene, both of which are very significant causal or
>predisposing factors in thrombosis requiring special attention.
>Mutations in the Factor V Leiden Gene
>Thrombosis may occur as strokes, deep vein thrombosis in the legs with
>or without pulmonary embolism, or in myocardial infarction.
>· The most common hereditary blood clotting disorder is due to a
>mutation in the Factor V Leiden gene.
>· Autosomal dominant mode of inheritance.
>· About 5.27% Caucasians have a mutation in this gene.
>· Ethnic differences exist in the carrier frequency of Factor V Leiden
>deficiency:
>· In Hispanic-Americans (2.21 %)
>· African-Americans (1.23%)
>· Asian-Americans (0.45%)
>· Native-Ameri cans (1.25%)
>· Risks of thrombosis - 7-fold in heterozygotes 80- fold in homozygotes
>· Risks of venous thromboembolism increase several hundred-fold in women
>homozygous for this mutation and using oral contraceptives,
>· About 20% of patients with a first episode of deep vein thrombosis
>have this Factor V missense mutation.
>· About 60% with recurrent thrombosis or pregnancy-associated
>thrombosis/embolism have this mutation.
>· Since the gene for Factor V Leiden and the antithrombin III gene are
>both located on the long arm of chromosome 1, these two deficiencies are
>frequently co-inherited!
>· Adverse Pregnancy Outcome Increased risk for severe preeclampsia (risk
>about double in women heterozygous for this mutation)
>· Increased frequency reported of recurrent pregnancy loss, recurrent
>intrauterine fetal deaths, intrauterine growth retardation, and
>increased likelihood of placental infarction
>· Women with the HELLP syndrome (hemolysis, elevated liver enzymes, low
>platelets) have a higher incidence of Factor V LeidE mutations,
>· In about 70% with this mutation, a second "hit" or factor is necessary
>for thrombosis to occur. Second "hits" include,
>- oral contraceptive use
>- surgery
>- trauma
>- homozygosity for this mutation
>- protein C deficiency
>- protein S deficiency
>- antithrombin III deficiency
>- presence of lupus anticoagulant
>- hyperhomocystinemia
>· Do DNA analysis for the Factor V Leiden mutation in
>- Patients with previous deep vein thrombosis
>- Those with family history of early age stroke
>- Patients with thromboembolism
>- Patients with hyperhomocystinuria
>· Clinical implications and risk management following discovery of
>Factor V Leiden mutation
>- Inquire about family history (including partners of deep
>veinthrombosis, early strokes, thromboembolism, early cardiac
>infarction.
>- Offer DNA analysis for this mutation if family history positive for
>any of these problems.
>- Also test women with unexplained recurrent pregnancy loss, stillbirth
>> 10% placental infarction and those with preeclampsia.
>- Avoid oral contraceptives. {Avoid liability and document
>advice).
>- Some patients may need long-term anticoagulant therapy. - Give
>optimal antithrombotic prophylaxis following surgery (including
>C-Section), following pregnancy and if there will be prolonged
>immobility.
>- Watch for a familv history of deep vein thrombosis. If positive
>history, test patient for Factor V Leiden mutation and recommend family
>be tested. Since about 1 in 20 women carry the Factor V Leiden
>mutation, consideration should be given to screening all Caucasians in
>the preconception period.
>· Inquire about family hx (including partners) of DVT, early strokes,
>thromboembolism, early cardiac infarction."
>
>--
>"Do not take life too seriously. You will never get out of it alive."
>
>Marianne Williamson
>
--
Ronald E. Ainsworth, MD
