Antithrombin testing and treatment in pregnancy: Their real-world relationship to clinical outcomes.

BACKGROUND: Antithrombin (AT) deficiency is a severe thrombophilia associated with increased rates of maternal morbidity, mortality, and greater healthcare resource utilization during pregnancy and postpartum. METHODS: Two large U.S. healthcare databases were queried for women aged 15-44 with delivery-related encounters: Cerner Real-World Data (CRWD, 01/01/2000-12/31/2021) and Premier Healthcare Database (PHD, 01/01/2016-01/01/2019). Individuals receiving cardiopulmonary bypass were excluded. Three cohorts were created: 1) Individuals who had AT levels tested any time between 9-months pre- through 3-months post-delivery (CRWD Test Cohort); 2) individuals prescribed AT concentrate (ATc) within 1-year pre- or 1-year post-delivery in CRWD (CRWD Medication Cohort); and 3) the same criteria as 2) applied to PHD (PHD Medication Cohort). RESULTS: There were 5411 individuals in the CRWD Test Cohort, 13 in the CRWD Medication Cohort and 38 in the PHD Medication Cohort. Demographic and baseline clinical characteristics were similar across cohorts. AT level testing occurred pre-delivery in 47.9 % of the CRWD Test Cohort and 23.1 % of the CRWD Medication Cohort. ATc was administered during the delivery hospitalization to 0.1 %, 23.1 % and 50.0 % of the CRWD Test, CRWD Medication, and PHD Medication Cohorts, respectively. Across cohorts, 5.4-7.9 % of individuals experienced thrombosis during the delivery-related encounter. Mean (SD) total costs for delivery through 1-year post-delivery were $190,894 ($276,893) with $123,763 ($177,122) of total costs related to abnormal coagulation. CONCLUSION: Opportunities exist to enhance the care of pregnant individuals with low AT levels throughout pregnancy, aiming for optimal maternal outcomes.

Warfarin Therapy and Percutaneous Left Atrial Appendage Closure for a Patient with Atrial Fibrillation and Antithrombin-III Deficiency.

Some patients develop ischemic stroke despite taking direct oral anticoagulants because of the presence of other risk factors such as coagulopathies. A 65-year-old male patient with non-valvular atrial fibrillation (NVAF) taking rivaroxaban was diagnosed as having embolic stroke and antithrombin-III (AT-III) deficiency. Echocardiography revealed a thrombus in the left atrial appendage (LAA). He was prescribed warfarin, and after resolution of the thrombus, we successfully performed percutaneous LAA closure (LAAC), with no subsequent recurrence or device-related thrombosis. Warfarin and LAAC may be feasible for NVAF patients with AT-III deficiency.

A Rare Case of Antiphospholipid Syndrome With Concomitant Antithrombin III Deficiency: A Case Report.

Antithrombin (AT) deficiency and antiphospholipid syndrome (APS) are distinct but potentially overlapping disorders with significant implications for thrombosis. We present a case of a 28-year-old male with hereditary AT deficiency who subsequently developed primary APS. Despite the challenges of overlapping symptoms and anticoagulation therapy, a careful diagnostic approach revealed the coexistence of these rare conditions. The patient was successfully managed with long-term anticoagulation, hydroxychloroquine, and other supportive measures. This case underscores the importance of comprehensive laboratory testing, especially when managing patients with pre-existing anticoagulation needs.

Case report: A case of new mutation in SERPINC1 leading to thrombotic microangiopathy.

Introduction: Hereditary antithrombin-III deficiency can significantly increase the risk for thrombosis, which is common in limb deep vein and pulmonary cases. However, thrombotic microangiopathy (TMA) caused by hereditary antithrombin deficiency is rare. Case Presentation: We reported the case of a 32-year-old Chinese female patient with TMA with renal injury caused by decreased antithrombin-III activity due to a new mutation (chr1-173884049 c.50A>G) in SERPINC1, which encodes antithrombin-III. In this case, the patient had no history of relevant drug use, diabetes, or monoclonal plasma cells in the bone marrow puncture. Consequently, TMA of the kidney was considered secondary to hereditary antithrombin-III deficiency. Gene detection was the only clue that led us to suspect that TMA was caused by hereditary antithrombin deficiency. Conclusion: Our findings indicated that for patients with repeated findings of antithrombin-III activity less than 50%, the possibility of antithrombin-III deficiency and complete gene detection must be considered immediately after excluding the use of anticoagulants and lack of availability to facilitate early detection, diagnosis, and intervention.

The addition of Tirofiban infusión to heparin for intraoperative heparin resistance associated with Marfan Syndrome / Adición de una infusión de Tirofiban a heparina en caso de resistencia intraoperatoria a la heparina asociada al Síndrome de Marfan

Abstract Marfan syndrome classically presents with aortic root aneurysms. Aortic ectasia causes diverse blood flow alterations, influencing the behavior of coagulation factors and platelet activity. Heparin resistance has also been reported associated with Marfan Syndrome in a small number of patients, probably due to antithrombin III (ATIII) deficiency or various mutations. The ascending aorta and the aortic valve are replaced with prosthetic material during Bentall- de Bonno procedures. Resistance to anticoagulation during extracorporeal circulation, represents a significant challenge for both anesthesiologists and the surgical team. Resistance to heparin was observed in a patient with Marfan syndrome undergoing a Bentall procedure. ATIII concentrate was not available, and Activated Coagulation Time did not increase despite high doses of heparin. An alternate anticoagulation approach was used successfully.

Resumen El síndrome de Marfan clásicamente se presenta con aneurismas de la raíz de la aorta. La ectasia aórtica produce alteraciones en el flujo sanguíneo que influyen sobre el comportamiento de los factores de la coagulación y la actividad de las plaquetas. También se ha reportado resistencia a la heparina asociada al Síndrome de Marfan en un menor número de pacientes, probablemente debido a deficiencia de antitrombina III (ATIII) o a diversas mutaciones. La aorta ascendente y la válvula aórtica se reemplazan con material prostético en los procedimientos Bentall- de Bonno. La resistencia a la anticoagulación durante circulación extracorpórea significa un enorme desafío tanto para los anestesiólogos, como para el equipo quirúrgico. Se observó resistencia a la heparina en un paciente con Síndrome de Marfan sometido a un procedimiento de Bentall. No había disponibilidad de concentrado ATIII y no aumentó el Tiempo de Coagulación Activada a pesar de las elevadas dosis de heparina. Se utilizó exitosamente un abordaje alterno de anticoagulación.

Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension.

Background: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. Objectives: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. Methods: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. Results: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Conclusions: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

Cardiac Arrest Due to Pulmonary Embolism After Posterior Spinal Fusion in a Patient With Acute Paraplegia Caused by a Metastatic Spinal Tumor Associated With Congenital Antithrombin III Deficiency.

Congenital antithrombin (AT) III deficiency has a high incidence of deep vein thrombosis and pulmonary embolism due to reduced anticoagulation. In this study, we report a case of a patient who experienced cardiac arrest due to pulmonary embolism after emergency posterior spinal fusion for acute paraplesia due to a metastatic spinal tumor associated with AT III deficiency. A 49-year-old man with a history of familial AT III deficiency visited our hospital due to difficulty in walking caused by a progressive paralysis of the lower limbs. Clinical examination revealed multiple bone metastases due to prostate cancer and spinal cord compression caused by a pathological fracture of the T1 vertebral body. He had low AT III activity levels and high D-dimer levels. The following day, he underwent posterior spinal decompression and fusion. However, he had pulmonary embolism with cardiac arrest three days after surgery. He recovered without sequelae after emergency thrombectomy following resuscitation. Patients with AT III deficiency who cannot walk due to a metastatic spinal tumor inevitably develop deep vein thrombosis and pulmonary embolism. To avoid lethal pulmonary embolism, preventing deep vein thrombosis should be prioritized before surgery, even in the presence of acute progressive paraplegia.

[Thrombosis of the inferior vena cava and right atrium in a neonate with thrombophilia: diagnosis, treatment, result]. / Tromboz nizhnei poloi veny i pravogo predserdiia u novorozhdennogo s trombofiliei: diagnostika, lechenie, rezul'tat.

Hereditary thrombophilia is rare pathology giving rise to a ninefold increase in the risk for the development of thromboembolism in infants. The problem is multifactorial and characterized by high mortality, especially in neonates. Infants who develop thrombosis, particularly those with no family history, are often subjected to testing for hereditary thrombophilia. However, genetic testing for thrombophilia does not change the plan of treatment but makes it possible to perform prevention of thrombosis within the risk periods for the patient. Poor awareness of paediatricians, the complexity of carrying out genetic testing, the absence of approaches supported by evidence-based medicine due to shortage of high-quality clinical trials and no guidelines on prevention of thromboembolism in infants, as well as the frequent occurrence of diversified causes and diseases in different age groups make the problem significant for modern medicine. Further studies are needed to address many unanswered as yet questions.

Successful treatment with rivaroxaban of an extended deep vein thrombosis complicated by pulmonary embolism in a patient with familial antithrombin III deficiency: a case report.

BACKGROUND: Patients with low levels of antithrombin III (AT III) are at an increased risk of developing arteriovenous thromboembolic disease. CASE SUMMARY: We report a case of a 28-year-old woman who presented with a 1-week history of spontaneous right calf pain and swelling. A heterozygous AT III deficiency, phenotypically expressed as deep vein thrombosis, was reported in the patient's mother and sister. Blood workup revealed residual AT III activity at 58% with normal protein C and protein S levels. Computed tomographic angiography (CTA) revealed subsegmental bilateral pulmonary embolism (PE) and deep vein thrombosis in the right leg extending into the inferior vena cava up to the confluence of the left renal vein. Placement of an inferior vena cava filter was not considered. Given the patient's haemodynamic stability, anticoagulant therapy with 15 mg of rivaroxaban twice a day was initiated instead. Echocardiography after 10 days of treatment revealed complete resolution of the thrombus located in the inferior vena cava, while CTA revealed complete resolution of the PE. DISCUSSION: Patients with AT III deficiency are likely to be heparin-resistant and will require higher heparin doses or the administration of AT III replacement therapy for the treatment of thrombosis, both of which are associated with an increased risk for haemorrhagic complications. Direct factor Xa inhibition by rivaroxaban provided an alternative mechanism for anticoagulation, which was found to be particularly useful in this patient with familial AT III deficiency, deep vein thrombosis, and PE.

Searching for genetic variants associated with thrombophilia.

Thrombotic states are inherited or acquired predisposition for thrombosis in the human vascular system. Nowadays Leiden mutation and mutation in prothrombin G20210A contributing to congenital thrombophilia are routinely tested. These mutations have a high prevalence in the population. Congenital deficiencies of protein S, protein C and antithrombin III are rare thrombophilia with lower population frequency, but higher risk of thromboembolic event. The genetic causes are mutations in the genes, which encode these proteins. The choice of proper molecular genetic testing depends on the difference in the detection of well-known single nucleotide polymorphism or unknown/rare variant. For the detection of causative variant FV Leiden and prothrombin G20210A are mostly used PCR-RFLP, reverse Strip Assay®, allele-specific PCR, TaqMan real-time PCR and SNaPshot®. Precise patient selection should precede the genetic testing of rare variants in anticoagulant proteins. It is appropriate to use methodology of massive parallel sequencing supplemented by a methodology for the detection of larger gene rearrangements - MLPA. We are successfully employing this approach in our institute. This methodology is faster with larger analytic capacity compared to commonly used direct sequencing by Sanger method.

Spontaneous Carotid Cavernous Fistula in Young Female with Anti-thrombin III Deficiency.

A 27-year-old female patient presented with headache, vomiting, and visual disturbances who was evaluated and detected to have a direct carotid cavernous fistula (CCF). Secondary causes were ruled out, and she was treated with coil occlusion and glue injection. A month after almost complete clinical recovery, she developed deep vein thrombosis of left thigh. Subsequent work-up revealed antithrombin III (ATIII) deficiency in her. To the best of our knowledge, this is the first reported case of ATIII deficiency associated with CCF. This case shows the importance of working up for a primary etiology if any, to prevent further complications after surgery.

A case report of atrial fibrillation in a patient with heparin resistance associated with an antithrombin III deficiency successfully treated by radiofrequency catheter ablation using a direct thrombin inhibitor.

BACKGROUND: Pulmonary vein antrum isolation has proven to be a useful strategy for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) worldwide. Anticoagulation therapies are necessary to avoid thromboembolic events before, during, and after RFCA of AF. During the RFCA procedure for AF, it is recommended that the activated coagulation time be maintained between 300 s and 400 s using heparin as an anticoagulation therapy. CASE SUMMARY: An 81-year-old man with symptomatic and drug-refractory paroxysmal AF underwent RFCA. We found that he had a severe heparin resistance during the RFCA procedure, and heparin had little effect on him. Thus, a direct thrombin inhibitor, Argatroban Hydrate®, was used instead of heparin for anticoagulation therapy during the procedure. Finally, the AF was successfully treated by RFCA without any complications. With a post-procedural inspection, we found that he had a Type-1 antithrombin III (AT-III) deficiency. DISCUSSION: Atrial fibrillation is the most common clinical arrhythmia and is associated with significant clinical morbidity and increased mortality. An AT-III deficiency is a well-known autosomal dominant hereditary disease and congenital blood coagulation abnormality occurring in about 1:500-5000 live births that may sometimes cause thrombophilia. Thus, the physicians may occasionally come across patients with an AT-III deficiency in real-world clinical practice, even though they have no history of thrombophilia. Argatroban Hydrate® may be effective and feasible for anticoagulation therapy during the RFCA procedure of AF in patients with heparin resistance such as in this present case.

SERPINC1 variants causing hereditary antithrombin deficiency in a Danish population.

INTRODUCTION: Antithrombin deficiency is associated with increased risk of venous thromboembolism (VTE). We aimed to identify variants causing antithrombin deficiency in a Danish population. MATERIALS AND METHODS: We performed Sanger sequencing and, in relevant cases, multiplex ligation-dependent probe amplification analyses, in 46 individuals (23 index cases) with and 9 relatives without antithrombin deficiency. Furthermore, in order to explore whether a combination of antithrombin type II heparin binding site (HBS) deficiency and factor V Leiden single nucleotide variant (SNV) conferred a higher risk of VTE than either risk factor alone, we performed genotyping for factor V Leiden in most of the carriers of type II HBS deficiency (n = 25). RESULTS: We detected causal variants in all 46 carriers: three large and two small deletions, all causing type I antithrombin deficiency, and seven SNVs: one causing type I, one causing type II reactive site (RS), four causing type II HBS and one causing pleiotropic effect (PE) type II antithrombin deficiency. None of the relatives without antithrombin deficiency had the family variant. All detected SNVs have been reported previously. Majority (n = 27) of carriers had type II HBS deficiency, most often caused by the p.(Pro73Leu) SNV (n = 19). Heterozygosity for factor V Leiden was observed in three (3/25 = 12%) carriers of type II HBS deficiency. Only four (4/25 = 16%) carriers of type II HBS antithrombin deficiency experienced VTE, and two of these were heterozygous for factor V Leiden. CONCLUSIONS: In a systematic search to identify variants causing hereditary antithrombin deficiency in a Danish population, we achieved a variant detection rate of 100%.

Monitoring of heparins in antithrombin-deficient patients.

INTRODUCTION: Heparins exert their anticoagulant effect through activation of antithrombin. Whether antithrombin deficiency leads to clinically relevantly reduced anti-Xa activity of heparins is unknown. We investigated the relation between antithrombin deficiency and anti-Xa activity measurements of plasma samples spiked with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). MATERIALS AND METHODS: Plasma samples from 34 antithrombin-deficient subjects and 17 family controls were spiked with UFH and LMWH (nadroparin) aimed to correspond with an anti-Xa activity of 0.8 IU/mL. Antithrombin, ß-antithrombin and anti-Xa activities were measured. RESULTS: Mean anti-Xa activity with LWMH was 0.55 IU/mL (0.30-0.74) (recovery 69%, 38-93%) in antithrombin-deficient subjects and 0.82 (0.71-0.89) IU/mL in controls (recovery 103%, 89-111%). Expected anti-Xa measurements after LMWH spiking were found in 17/17 non-deficient subjects and in 8/34 antithrombin-deficient subjects. Anti-Xa measurements in the expected range (0.6-1.0 IU/mL) after UFH spiking were found in 17/17 non-deficient subjects and in 1/22 antithrombin-deficient subjects. Antithrombin activity correlated with anti-Xa activity of UFH (R = 0.77) and LMWH (R = 0.66). Mixing studies of pooled normal plasma and antithrombin-deficient plasma showed that anti-Xa recovery was linearly reduced with antithrombin activity decreasing below 100%. CONCLUSIONS: Reduced antithrombin activity causes significantly reduced anti-Xa levels. Standard LWMH- or UFH-doses are likely to lead to under treatment in antithrombin-deficient individuals.

Strategy for Cardiovascular Surgery in Patients with Antithrombin III Deficiency.

Antithrombin III (ATIII) deficiency is a rare disorder in which thrombosis can be induced by stimuli that do not usually lead to thrombus formation, including minor injuries and surgery. Therefore, patients with ATIII deficiency undergoing cardiovascular surgery that involves heparinization require careful perioperative management. We experienced five patients with ATIII deficiency who underwent cardiovascular surgery and were managed with ATIII replacement. By administration of ATIII concentrate, preoperative ATIII activity was maintained at ≥120% and postoperative ATIII activity at ≥80%. All five patients were treated successfully without postoperative complications such as hemorrhage or thrombosis. In patients with ATIII deficiency undergoing cardiac surgery, it is important to perform ATIII replacement to achieve preoperative ATIII activity ≥120% and postoperative ATIII activity ≥80%, while the activated clotting time (ACT) is maintained at >400 seconds during cardiopulmonary bypass. In addition, long-term postoperative anticoagulant therapy is necessary in hereditary ATIII deficiency patients with a history of thrombosis.

Successful treatment of a massive pulmonary embolism using rivaroxaban in a patient with antithrombin III deficiency.

We report a case of acute massive pulmonary embolism in a patient with antithrombin III deficiency. The patient was treated with rivaroxaban. The patient responded well to the therapy, and contrast-enhanced computed tomography showed nearly complete disappearance of the pulmonary embolism. Patients with low antithrombin III activity may have resistance to heparin therapy, leading to insufficient anticoagulation during the acute phase of thromboembolism. This case suggests that direct oral anticoagulants, such as rivaroxaban, may be effective first-line agents for treating venous thromboembolism in patients with antithrombin III deficiency. .

Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect.

UNLABELLED: Essentials We investigated the molecular base of antithrombin deficiency in cases without SERPINC1 defects. 27% of cases presented hypoglycosylation, transient in 62% and not restricted to antithrombin. Variations in genes involved in N-glycosylation underline this phenotype. These results support a new form of thrombophilia. Click here to listen to Dr Huntington's perspective on thrombin inhibition by the serpins SUMMARY: Background Since the discovery of antithrombin deficiency, 50 years ago, few new thrombophilic defects have been identified, all with weaker risk of thrombosis than antithrombin deficiency. Objective To identify new thrombophilic mechanisms. Patients/methods We studied 30 patients with antithrombin deficiency but no defects in the gene encoding this key anticoagulant (SERPINC1). Results A high proportion of these patients (8/30: 27%) had increased hypoglycosylated forms of antithrombin. All N-glycoproteins tested in these patients (α1-antitrypsin, FXI and transferrin) had electrophoretic, HPLC and Q-TOF patterns indistinguishable from those of the congenital disorders of glycosylation (rare recessive multisystem disorders). However, all except one had no mental disability. Moreover, intermittent antithrombin deficiency and hypoglycosylation was recorded in five out of these eight patients, all associated with moderate alcohol intake. Genetic analysis, including whole exome sequencing, revealed mutations in different genes involved in the N-glycosylation pathway. Conclusions Our study provides substantial and novel mechanistic insights into two disease processes, with potential implications for diagnosis and clinical care. An aberrant N-glycosylation causing a recessive or transient antithrombin deficiency is a new form of thrombophilia. Our data suggest that congenital disorders of glycosylation are probably underestimated, especially in cases with thrombosis as the main or only clinical manifestation.

Founder effect is responsible for the p.Leu131Phe heparin-binding-site antithrombin mutation common in Hungary: phenotype analysis in a large cohort.

BACKGROUND: Antithrombin (AT) is a key regulator of the coagulation. In type II deficiency, the heparin-binding-site defect (type II HBS) is considered to be relatively low thrombosis risk. OBJECTIVES: Our aims were to search for SERPINC1 mutation(s) and to describe the clinical and laboratory phenotype of a large number of AT Budapest3 (ATBp3, p.Leu131Phe) carriers and confirm the presence of a founder effect. PATIENTS/METHODS: AT-deficient patients were recruited and carriers of ATBp3, n = 102 (63 families) were selected. To investigate the founder effect, eight intragenic single nucleotide polymorphisms, a 5'-length dimorphism, and five microsatellite markers were detected. Clinical and laboratory data of the patients were collected and analyzed. RESULTS: In AT deficiency, 16 different causative mutations were found, and the great majority of patients were of type II HBS subtype. Most of them (n = 102/118, 86.5%) carried the ATBp3 mutation. The ATBp3 mutant allele was associated with one single haplotype, while different haplotypes were detected in the case of normal allele. The anti-factor Xa-based AT activity assay that we used could detect all ATBp3 patients with high sensitivity in our cohort. ATBp3 homozygosity (n = 26) was associated with thrombosis at a young age and conferred a high thrombotic risk. Half of the heterozygotes (n = 41/76, 53.9%) also had venous and/or arterial thrombosis, and pregnancy complications were also recorded. CONCLUSION: In Hungary, the founder mutation, ATBp3, is the most common AT deficiency. Our study is the first in which the clinical characterization of ATBp3 mutation was executed in a large population.

Manejo obstétrico de la deficiencia hereditaria de antitrombina durante el embarazo y puerperio. Dos casos clínicos / Obstetric management of hereditary antithrombin deficiency in pregnancy and postpartum. Two case studies

La deficiencia de antitrombina III hereditaria es una rara enfermedad que afecta al 0.02-0.2 por cento de la población. Puede presentar mayor frecuencia de complicaciones y resultados adversos tanto en la madre como en el feto. Se presenta el manejo obstétrico de dos gestaciones consecutivas en una mujer con deficiencia de antitrombina III. Descripción: en ambos embarazos la madre realiza profilaxis de la enfermedad tromboembólica con heparina de bajo peso molecular para evitar la aparición de esta patología tanto en el embarazo como en el puerperio y mejorar el flujo útero-placen-tario. Con respecto a las complicaciones obstétricas, sólo existe un enlentecimiento del crecimiento fetal que obliga a un control obstétrico estricto. En ambas gestaciones los estudios eco-Doppler están dentro de la normalidad lo que permite una conducta expectante, consiguiendo llegar a término. Discusión: la profilaxis con heparina de bajo peso molecular en las gestantes con esta trombofilia y las intervenciones preventivas de factores de riesgo de enfermedad tromboembólica, junto con un control obstétrico adecuado, ha conseguido evitar la apari-ción de complicaciones derivadas de esta patología en el embarazo y en el puerperio. Por otra parte, el control del crecimiento fetal y el estudio Eco-Doppler han permitido asegurar el bienestar fetal no adelan-tando el parto, consiguiendo partos a término...

Hereditary antithrombin III deficiency is a rare disease that affects 0.02-0.2 percent of the population. It may be associated with a higher rate of complications and adverse outcomes in both mother and fetus. The present study describes the management of a woman with antithrombin III deficiency and two consecutive pregnancies. Description: in both pregnancies, the woman under went prophylaxis with low molecular weigh heparin, to prevent thromboembolic disease and improve the utero-placental flow during pregnancy and the postpartum period. The only obstetric compli-cation was fetal growth retardation requiring strict obstetric control. In these two cases the eco-Doppler studies offeto-placentalflow were normal, leading to the expectation of managing a term birth. Discussion: low molecular weigh heparin prophylaxis in pregnant women with thrombophilia and preventive interventions for risk factors for throm-boembolic disease, together with appropriate obstetric care managed to avoid the emergence of complications of this disease in pregnancy and puer-perium. Fetal growth control and a Doppler study also help to ensure the well-being of the fetus and avoid a preterm birth...