I. Introduction

Throughout an entire normal pregnancy, the mother's ability to produce blood clots in the uterus and the placenta is suppressed. Non-clotting blood freely flows to and nourishes the baby. Some mothers may have certain conditions, both acquired and inherited, where clotting of the blood nourishing the baby is not suppressed. This increased tendency for the blood to clot is called thrombophilia. The resulting clots may cause the following complications to occur:

1. Implantation failure
2. Miscarriages
3. Pre-eclampsia
4. Intrauterine growth retardation
5. Oligohydramnios (low levels of amniotic fluid) 6. Abruptio placenta
7. Premature labor (often caused incompetent cervix syndrome)
8. Unexplained intrauterine fetal death
9. Thrombophlebitis (blood clots in the veins or the arteries during pregnancy)

Any woman experiencing any of these complications needs to be evaluated for thrombophilia.

At the time of attachment of the embryo with the endometrium, the endometrium has reached a certain thickness of (10-14 mm link uterine biophysical profile) and blood vessels have grown into zone three, the top most layer of the endometrium. The hormones of ovulation have opened these blood vessels wider than others and the blood flow never stops. Within 24 hours of attachment the embryo (placental cells) have found these blood vessels, bored into them, opened them up and the nourishment process for the baby begins. In this document we discuss how inherited or acquired thrombophilia can cause the blood to begin to clot off and starve the embryo. This may occur either early or late in pregnancy. This is why you see the long list above of nine complications that can occur when this happens.

Once diagnosed as acquired or inherited, thrombophilia can be treated and healthy, normally grown babies can be born. The treatment for each is different.

II. Diagnosis of Inherited Thrombophilia

1. Lieden Factor V mutation R560Q (DNA test by PCR);
2. Hyperhomocysteinemia MTHFR C677T and A1298C mutations (DNA test by PCR);
3. Prothrombin Gene Mutation 20210 (GA) DNA test by PCR;
4. Protein C levels;
5. Protein S levels; and
6. Activated Protein C activity.
7. PAI-1 gene mutation
8. Factor XIII mutation

These tests can be done by most local laboratories.

III. Diagnosis of Acquired Thrombophilia (Antiphospholipid Antibodies) Return to Contents

1. Antibodies to six phospholipids of the IgM, IgG and IgA classes;
2. Lupus anticoagulant antibody;
3. Russell Viper Venom Time;
4. Activated Partial Thromboplastin Time (APTT);
5. and Prothrombin Time (PT), Partial Prothrombin Time (PTT).

These laboratory assays are available to doctors dealing with most reference laboratories. If assistance is needed, please This e-mail address is being protected from spambots. You need JavaScript enabled to view it .

IV. Evaluation of the Placenta from Complicated Pregnancies Return to Contents

Slides and paraffin blocks of the placenta are saved in the pathology department of the hospital that served the patient when the baby was born or lost. Registered patients can send these blocks to me for immune pathology. Clotting in the placenta or the blood vessels to the uterus can be diagnosed by doing immune pathology. Couples are encouraged to ask pathologists to send these blocks for study before embarking on another pregnancy since the most effective treatment must be initiated during the cycle of conception before the baby is conceived.

V. Advice

Since patients with inherited thrombophilia suffer clotting complications throughout life with a higher frequency than those without, monitoring for this complication is essential. The incidence of clotting disorders is from eight to 40 times higher than in patients without the thrombophilia disorder. Women with thrombophilia should

* have their children tested so that life style or dietary changes can be made from the beginning.
* choose contraception other than birth control pills.
* see a hematologist and check if you need anticoagulation treatment.
* consult with a hematologist if facing a surgical procedure, prolonged inactivity or if experienceing an injury or a fracture.
* alert other female family members of the inherited condition and urge testing of relatives prior to initiating a pregnancy.

VII. Conclusions

Thrombophilia, inherited or acquired, is very common. Any woman experiencing any of the above complications of pregnancy deserves to be tested. Any relative of any woman experiencing the above complications should demand testing before a pregnancy is planned or initiated.

Much of the information in this simple document is very new. Many doctors who deal with pregnant women may not know about this problem. We are living in an age where up-to-date information is readily available to the consumer. Most individuals are sufficiently bright and capable to begin to collect information about the problems they have experienced and understand this information.

The reproductive system is incredibly overbuilt for success and when it fails, something is surely wrong. We do not have all the answers but we have answers to many of them. Preventive medicine, often required during the cycle of conception, can insure the safe arrival of your child in your home after you have experienced an incredibly long and disappointing journey of trying.

Thrombophilia is much more common in women than in men. Perhaps there is survival advantage to women to have thrombophilia. Perhaps they are less prone to die of post partum hemorrhage, the chief cause of death in pregnant women.

VIII. References

1 Kupferminc MJ, Eldor A, Steinman N, Many A, Barm A, Jaffa A, Fait G, Lessing JB: Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999;340:9–13.

2 Coulam CB, Jeyendran RS, Fishel LA, Roussev R: Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol 2006; 55:360–368.

3 Goodman CS, Coulam CB, Jeyendran RS, Acosta VA, Roussev R: Which thrombophilic gene mutations are risk factors for recurrent pregnancy loss? Am J Reprod Immunol 2006; 56:230–236.

4 Cowchock S: Antiphospholipid antibody syndrome. Lupus 1998; 7(Suppl. 2):S95–S97. 5 Qublan HS, Eid SS, Ababneh HA, Amarin ZO, Smadi AZ, Al-Khafaji FF, Khader YS: Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Hum Reprod 2006; 21:2694–2698.

6 Kutteh WH: Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol 1996; 174:1584–1589.

7 De Carolis S, Ferrazzani S, De Stefano V, Garofalo S, Fatigante G, Rossi E, Leone G, Caruso A: Inherited thrombophilia: treatment during pregnancy. Fetal Diagn Ther 2006; 21:281–286.

8 Sarto A, Rocha M, Geller M, Capmany C, Martinez M, Quintans C, Donaldson M, Pasqualini RS:Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia. Medicina (B Aires) 2001; 61:406–412.

9 Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis JS: Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 2000; 83:693–697.

10 Noble LS, Kutteh WH, Lashey N, Franklin RD, Herrada J: Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil Steril 2005; 83:684–690.

11 Kupferminc, JF, Eldor, A. et al : Increased frequency of Genetic Thrombophilia in Women with complications of Pregnancy. New England Journal of Medicine 1999; 340 pp 9-13.