**Meet the editor**

Dr. Petar Ivanov has been involved in maternal thrombophilia state field since 2002. Initially, his PhD degree concerns the indication and individualization in Venous Thromboembolism inherited thrombophilia testing. Subsequently, based on more than 5000 consequently investigated women with pregnancy complications, he has published a repeatedly updated, expanded, and

frequently quoted recommendations for acquired / inherited thrombophilia panel testing. Currently, as OB/GYNs in a private IVF clinic, Pleven, Bulgaria, he is specializing in adverse gestation outcome treatment, which gives rare chance to match laboratory work with daily high risk pregnancies follow up.

Contents

**Preface VII**

Ludek Slavik

Chapter 1 **Genetics and Molecular Pathophysiology of**

P. Ivanov and Tsv. Tsvyatkovska

**Thrombophilia Testing 39**

**and Heparin 83**

Penkova

Chapter 2 **Placenta Changes During Pregnancy with Thrombophilia —**

Chapter 3 **Main Types of Clinical Appearance of Thrombophilic States**

Chapter 4 **Pharmacogenetics and the Treatment of Thrombophilia 67** Ivana Novaković, Nela Maksimović and Dragana Cvetković

Chapter 5 **Antiphospholipid Antibodies Syndrome and Reproductive Failures: New Therapeutic Trends Beyond Aspirin**

Chiara Tersigni, Silvia D'Ippolito and Nicoletta Di Simone

**Multiple Mechanisms and Resultant Clinical Outcomes 105**

P. Ivanov, Sl. Tomov, Tsv. Tsvyatkovska, E. Konova and R. Komsa-

Chapter 6 **Thrombophilia in Systemic Lupus Erythematosus: A Review of**

Chapter 7 **Thrombophilia in Assisted Reproductive Technology — Place**

**and Needs of Thromboprophylaxis 129**

Patricia J. Dhar and Robert J. Sokol

**During Pregnancy – Target Groups for**

**Influences of Low Molecular Weight Heparin Therapy 25**

Ricardo Barini, Joyce Annichino-Bizzache, Egle Couto, Marcelo Luis

Nomura, Adriana Goes Soligo and Isabela Nelly Machado

**Thrombotic States 1**

## Contents

## **Preface XI**



Preface

health involved practitioners.

and placenta.

anticoagulant treatment.

assisted reproduction.

Thrombophilia has appeared as a diverse group coagulation disorder associated with thrombosis development tendency. Both acquired and inherited thrombophilia shows relationship with a risk of pregnancy failure. Despite the extended researches, the influence of thrombophilia on gestation complications and potential management op‐

The main purpose of "Pregnancy Thrombophilia - The Unsuspected Risk" is to provide an update of the current statements of the place and treatment options of thrombophilic conditions during pregnancy. The thrombotic state and its control during pregnancy appears in a new direction in high risk pregnancy follow up. Providing continuous up‐ dated evidence concerning these pregnancy states is a sizable goal of mother-fetus

The authors of "Pregnancy Thrombophilia - The Unsuspected Risk" attempt to propose up-to-date, concise statements about pregnancy thrombophilia and current indications for treatment options encompassing both clinical and basic knowledge of the problem. The first and second book's chapters provide recent knowledge about molecular basis of thrombophilia state and its clinical and pathological appearance in mother, fetus,

The further two chapters discuss the main target groups of women with pregnancy complications needing thrombophilia testing and an incoming pharmacogenetic ap‐

Chapters five and six summarize the current view for the place of acquired thrombo‐ philia – antiphospholipid antibody syndrome and systemic lupus erythematosus dis‐ ease in adverse pregnancy outcome and supplemental therapy in concern with

Because of the specific processes concerning embryo implantation and placenta devel‐ opment after IVF, a separate chapter has been added to give contemporary position for the influence and treatment requirements in women with thrombophilia undergoing

Thanks to the different affiliation fields of the book's authors and editors, an extensive view of pregnancy thrombophilia conditions have been given using current published

"Pregnancy Thrombophilia - The Unsuspected Risk" has been faced to all specialists, being involved in mother-fetal health care and it gives a chance for them to form their

tions stays indistinct and undergoes frequent revaluations.

proach of individualized antithrombotic therapy.

clinical trials and still-in-laboratory investigations.

## Preface

Thrombophilia has appeared as a diverse group coagulation disorder associated with thrombosis development tendency. Both acquired and inherited thrombophilia shows relationship with a risk of pregnancy failure. Despite the extended researches, the influence of thrombophilia on gestation complications and potential management op‐ tions stays indistinct and undergoes frequent revaluations.

The main purpose of "Pregnancy Thrombophilia - The Unsuspected Risk" is to provide an update of the current statements of the place and treatment options of thrombophilic conditions during pregnancy. The thrombotic state and its control during pregnancy appears in a new direction in high risk pregnancy follow up. Providing continuous up‐ dated evidence concerning these pregnancy states is a sizable goal of mother-fetus health involved practitioners.

The authors of "Pregnancy Thrombophilia - The Unsuspected Risk" attempt to propose up-to-date, concise statements about pregnancy thrombophilia and current indications for treatment options encompassing both clinical and basic knowledge of the problem.

The first and second book's chapters provide recent knowledge about molecular basis of thrombophilia state and its clinical and pathological appearance in mother, fetus, and placenta.

The further two chapters discuss the main target groups of women with pregnancy complications needing thrombophilia testing and an incoming pharmacogenetic ap‐ proach of individualized antithrombotic therapy.

Chapters five and six summarize the current view for the place of acquired thrombo‐ philia – antiphospholipid antibody syndrome and systemic lupus erythematosus dis‐ ease in adverse pregnancy outcome and supplemental therapy in concern with anticoagulant treatment.

Because of the specific processes concerning embryo implantation and placenta devel‐ opment after IVF, a separate chapter has been added to give contemporary position for the influence and treatment requirements in women with thrombophilia undergoing assisted reproduction.

Thanks to the different affiliation fields of the book's authors and editors, an extensive view of pregnancy thrombophilia conditions have been given using current published clinical trials and still-in-laboratory investigations.

"Pregnancy Thrombophilia - The Unsuspected Risk" has been faced to all specialists, being involved in mother-fetal health care and it gives a chance for them to form their own opinion for studying and treating maternal thrombophilic state. The content is open for feedback, concerning further update, improvement of the scientific substance and applied clinical guidelines directions.

#### **Petar Ivanov, MD, PhD, OB/GYNs**

**Chapter 1**

**Genetics and Molecular Pathophysiology of Thrombotic**

Venous thrombosis is a multifactorial disease frequently related to the interaction of genetic and environmental risk factors. Testing for specific mutations in these patients helps to determine the decision on the duration of anticoagulant therapy, risk stratification for primary or secondary prophylaxis. Some of the recently discovered genetic risk factors, such as factor V Leiden and prothrombin G20210A mutations, are quite common in the population. When compared to functional assays, molecular assays provide clear results without different cutoff values. Accordingly, laboratory investigation of thrombophilic disorders has expanded due to incorporation of modern molecular assays. Criteria used to select specific DNA methodol‐ ogies reflect the issues of cost, automation, speed, reliability, and simplicity for specific diagnostics. A variety of currently used molecular methods fulfill many, but not all of these criteria. The new methods of real-time PCR and DNA microarrays offer the potential for widespread application and utility in the future. Problems arise with interpretation in many

Let's look at the history of molecular diagnosis of thrombophilia. Since the very beginning of the diagnosis of thrombophilic disorders, which arose from the study of families with a high frequency of thrombophilic complications, it was apparent that in a number of cases, the disorder was due to dominantly inherited conditions. Already the discovery of the first families presenting a defect in antithrombin (AT) led to the description of the genetic causes

Molecular genetic methods were implemented into the screening examinations for thrombo‐ philic disorders in the 1990's along with the first discoveries of coagulation inhibitors (AT, protein C and protein S). The discovery of the molecular cause of activated protein C (APC)

and reproduction in any medium, provided the original work is properly cited.

© 2013 Slavik; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

**States**

Ludek Slavik

**1. Introduction**

http://dx.doi.org/10.5772/56528

Additional information is available at the end of the chapter

new polymorphisms without significant clinical relevance.

of this defect. As such, over 150 causes of AT mutation were described.

resistance by Bertina in 1994 greatly expanded their utilization.

Clinical Institute for Reproductive Medicine, IVF Unit Medical University Pleven, Biochemistry Department Pleven, Bulgaria

**Chapter 1**
