ABSTRACT
BACKGROUND: Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE). METHODS: Among 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months. RESULTS: Among the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45-36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001). CONCLUSIONS: About 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.
Subject(s)
Antithrombin III Deficiency/physiopathology , Conjunctivitis/physiopathology , Plasminogen/deficiency , Protein C Deficiency/physiopathology , Protein S Deficiency/physiopathology , Skin Diseases, Genetic/physiopathology , Thrombophilia/physiopathology , Venous Thromboembolism/physiopathology , Adult , Aged , Antithrombin III/genetics , Antithrombin III Deficiency/complications , Antithrombin III Deficiency/diagnosis , Antithrombin III Deficiency/genetics , Conjunctivitis/complications , Conjunctivitis/diagnosis , Conjunctivitis/genetics , Female , Gene Expression , Humans , Male , Middle Aged , Plasminogen/genetics , Protein C/genetics , Protein C Deficiency/complications , Protein C Deficiency/diagnosis , Protein C Deficiency/genetics , Protein S/genetics , Protein S Deficiency/complications , Protein S Deficiency/diagnosis , Protein S Deficiency/genetics , Republic of Korea , Retrospective Studies , Sequence Analysis, DNA , Skin Diseases, Genetic/complications , Skin Diseases, Genetic/diagnosis , Skin Diseases, Genetic/genetics , Thrombophilia/diagnosis , Thrombophilia/etiology , Thrombophilia/genetics , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Venous Thromboembolism/geneticsABSTRACT
Protein S (PS) is a vitaminK-dependent glycoproteinwhich plays an important role in the regulation of blood coagulation. PS deficiency has been found in 1.5-7% of thrombophilic patients. Here, we report the first Polish case with PS deficiency caused by the p.Arg451* in the PROS1 gene detected in a 21-year-old man with trauma-induced venous thromboembolism. To our knowledge, we provided the review of all the available data on this mutation (a total of 56 cases). The proband, his mother and his sister were screened for thrombophilia. To elucidate genetic background of PS deficiency, all PROS1 genes were subjected to direct sequencing. The free PS levels were 35% in the proband, 21% in the proband's mother and 28% in the proband's sister and their PS total levels were 37.1, 47.5 and 55.1%, respectively. Type I PS deficiency was diagnosed. In all patients, genetic analysis revealed the presence of heterozygous nonsense mutation (c.1351C>T; p.Arg451*) located in exon 12 of PROS1 gene. This mutation interrupts the reading frame by premature termination codon at position 451 and may lead to the production of truncated protein. The present case combined with the review of the literature suggests that p.Arg451* in the PROS1 gene mainly leads to clinically evident thrombosis following trauma, surgery or serious comorbidities especially malignancy.
Subject(s)
Blood Proteins/genetics , Protein S Deficiency/genetics , Venous Thromboembolism/genetics , Exons/genetics , Female , Humans , Male , Mutation , Pedigree , Poland , Protein S/genetics , Protein S Deficiency/physiopathology , Venous Thromboembolism/physiopathology , Young AdultABSTRACT
INTRODUCTION: In adolescents, the occurrence of priapism is commonly related to sickle cell disease and rarely to other causes. We hereby report a case of priapism due to an acquired protein S (PS) deficiency. AIM: The aim of this study was to describe a young man who developed a priapism with a thrombosis of the corpora cavernosa associated with an anti-PS antibody (anti-PS Ab). METHODS: One week after the onset of an influenza-like illness, a young male developed multiple extensive venous thromboses including a thrombosis of the corpora cavernosa causing painful partial priapism. These thromboses along with purpuric lesions with necrotic vesicles of the feet skin were linked to an acquired PS deficiency due to an anti-PS Ab. The optimal treatment of anti-PS Ab-associated thrombosis is debated but we chose to initiate (i) heparin; (ii) corticosteroids; and (iii) plasmapheresis. RESULTS: Even if priapism lasted more than 4 days, a full recovery of erectile function was observed within 3 months. As compared with priapism due to sickle cell disease, which is commonly associated with definitive erectile dysfunction, this favorable outcome is noteworthy. The skin healing was complete only 6 months later. CONCLUSION: Acquired PS deficiency complicating an infectious disease is a rare, life-threatening condition, associated with substantial morbidity related to amputations of limbs or digits. This is the first report of priapism due to acquired PS deficiency.
Subject(s)
Autoantibodies/adverse effects , Priapism/etiology , Protein S Deficiency/complications , Protein S/immunology , Adolescent , Humans , Male , Penis/physiopathology , Protein S Deficiency/physiopathologyABSTRACT
Dural arteriovenous fistula (DAVF) may present with a variety of neurological symptoms, ranging from tinnitus to fatal hemorrhage. We report a case of rapidly progressive cognitive impairment due to cerebral venous engorgement that reversed after endovascular treatment in a patient with DAVF, cerebral sinus thrombosis and protein S deficiency. DAVF may be a cause of vascular cognitive impairment and should be considered particularly in cases with a rapidly progressive course because they are potentially treatable.
Subject(s)
Central Nervous System Vascular Malformations/physiopathology , Central Nervous System Vascular Malformations/therapy , Cognition Disorders/physiopathology , Protein S Deficiency/physiopathology , Sinus Thrombosis, Intracranial/physiopathology , Aged , Angiography, Digital Subtraction , Brain/pathology , Central Nervous System Vascular Malformations/pathology , Cerebral Angiography , Cognition Disorders/diagnosis , Cognition Disorders/pathology , Cognition Disorders/therapy , Disease Progression , Embolization, Therapeutic , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Protein S Deficiency/pathology , Sinus Thrombosis, Intracranial/pathologyABSTRACT
TITLE: Reoclusion arterial recurrente tras recanalizacion endovascular en un paciente con deficit de proteina S.
Subject(s)
Carotid Artery Thrombosis/etiology , Endovascular Procedures , Infarction, Middle Cerebral Artery/etiology , Protein S Deficiency/complications , Thrombectomy , Adult , Angiography, Digital Subtraction , Animals , Aphasia/etiology , Carotid Artery Thrombosis/diagnostic imaging , Carotid Artery Thrombosis/surgery , Combined Modality Therapy , Decompression, Surgical , Dogs , Heparin/therapeutic use , Humans , Infarction, Anterior Cerebral Artery/diagnostic imaging , Infarction, Anterior Cerebral Artery/etiology , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/surgery , Male , Paresis/etiology , Protein S Deficiency/physiopathology , Rats , Recurrence , Reperfusion , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic useABSTRACT
OBJECTIVES: The clinical relevance of protein S deficiency in pregnant women remains controversial. Major debate exists regarding which parameter (total protein S antigen, free protein S antigen or functional protein S) should be evaluated in order to define protein S deficiency. The present study aimed to identify which of these parameters correlate with intrauterine growth restriction (IUGR). STUDY DESIGN: A retrospective case-control study of women with IUGR (n=27) and healthy controls (n=123) in the third trimester of pregnancy. RESULTS: The maternal serum of women in the IUGR group had significantly lower levels of functional and free protein S compared with the control group: 54.07 ± 24.72% vs 65.20 ± 17.95% (p<0.005) and 42.88 ± 11.01% vs 56.64 ± 13.30% (p<0.0001), respectively. No significant correlation was found between total protein S and IUGR. CONCLUSIONS: Levels of functional and free protein S are correlated with IUGR.
Subject(s)
Fetal Growth Retardation/blood , Fetal Growth Retardation/etiology , Pregnancy Proteins/blood , Protein S Deficiency/physiopathology , Protein S/analysis , Adult , Blood Coagulation Tests , Case-Control Studies , Female , Fetal Growth Retardation/diagnosis , Humans , Ligands , Pregnancy , Pregnancy Proteins/metabolism , Pregnancy Trimester, Third , Protein S/metabolism , Protein S Deficiency/blood , Protein S Deficiency/diagnosis , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Protein S deficiency (PSD) is an inherited or acquired disorder associated with an increased risk of thrombosis. We describe the unusual case of a previously healthy 45-year-old man with PSD. The patient was admitted for work-up of hematochezia and was diagnosed with colorectal cancer. Preoperative evaluation was unremarkable, and he subsequently underwent an uneventful laparoscopic total colectomy. The next day, he complained of chest tightness, and a computed tomography enterography revealed acute thrombosis throughout the entire superior mesenteric vein. Further laboratory evaluation revealed decreased free protein S levels. Polymerase chain reaction and direct sequencing of the PROS1 gene revealed a heterozygous transition (NM_000313.3 c.1907Aâ>âG), resulting in an amino acid change (p.Tyr636Cys). Although several case reports have described mesenteric venous thrombosis (MVT) in individuals with PSD, most have just reported decreases in the activity or concentration of protein S. We confirmed a nucleotide alteration of PROS1 associated with PSD. This patient, who had hereditary thrombophilia, may have developed MVT after transient exposure to abdominal surgery. We may need to implement more comprehensive coagulation testing prior to surgery considering the prevalence and possible risk of thromboembolic event.
Subject(s)
Adenocarcinoma/surgery , Colectomy/adverse effects , Colorectal Neoplasms/surgery , Protein S Deficiency/blood , Protein S/analysis , Thrombophilia/blood , Venous Thrombosis/blood , Adenocarcinoma/pathology , Blood Coagulation Tests , Blood Proteins/genetics , Colorectal Neoplasms/pathology , Heterozygote , Humans , Male , Mesenteric Veins/diagnostic imaging , Mesenteric Veins/physiopathology , Middle Aged , Point Mutation , Protein S Deficiency/complications , Protein S Deficiency/diagnostic imaging , Protein S Deficiency/genetics , Protein S Deficiency/physiopathology , Radiography , Thrombophilia/complications , Thrombophilia/diagnostic imaging , Thrombophilia/genetics , Thrombophilia/physiopathology , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Venous Thrombosis/genetics , Venous Thrombosis/physiopathologyABSTRACT
Protein C (PC) and protein S (PS) are vitamin K-dependent glycoproteins that play an important role in the regulation of blood coagulation as natural anticoagulants. PC is activated by thrombin and the resulting activated PC (APC) inactivates membrane-bound activated factor VIII and factor V. The free form of PS is an important cofactor of APC. Deficiencies in these proteins lead to an increased risk of venous thromboembolism; a few reports have also associated these deficiencies with arterial diseases. The degree of risk and the prevalence of PC and PS deficiency among patients with thrombosis and in those in the general population have been examined by several population studies with conflicting results, primarily due to methodological variability. The molecular genetic background of PC and PS deficiencies is heterogeneous. Most of the mutations cause type I deficiency (quantitative disorder). Type II deficiency (dysfunctional molecule) is diagnosed in approximately 5%-15% of cases. The diagnosis of PC and PS deficiencies is challenging; functional tests are influenced by several pre-analytical and analytical factors, and the diagnosis using molecular genetics also has special difficulties. Large gene segment deletions often remain undetected by DNA sequencing methods. The presence of the PS pseudogene makes genetic diagnosis even more complicated.
Subject(s)
Protein C Deficiency/genetics , Protein S Deficiency/genetics , Blood Coagulation/physiology , Genotype , Humans , Phenotype , Protein C Deficiency/epidemiology , Protein C Deficiency/physiopathology , Protein S Deficiency/epidemiology , Protein S Deficiency/physiopathologyABSTRACT
Protein S (ProS) is a blood anticoagulant encoded by the Pros1 gene, and ProS deficiencies are associated with venous thrombosis, stroke, and autoimmunity. These associations notwithstanding, the relative risk that reduced ProS expression confers in different disease settings has been difficult to assess without an animal model. We have now described a mouse model of ProS deficiency and shown that all Pros1-/- mice die in utero,from a fulminant coagulopathy and associated hemorrhages. Although ProS is known to act as a cofactor for activated Protein C (aPC), plasma from Pros1+/- heterozygous mice exhibited accelerated thrombin generation independent of aPC, and Pros1 mutants displayed defects in vessel development and function not seen in mice lacking protein C. Similar vascular defects appeared in mice in which Pros1 was conditionally deleted in vascular smooth muscle cells. Mutants in which Pros1 was deleted specifically in hepatocytes, which are thought to be the major source of ProS in the blood, were viable as adults and displayed less-severe coagulopathy without vascular dysgenesis. Finally, analysis of mutants in which Pros1 was deleted in endothelial cells indicated that these cells make a substantial contribution to circulating ProS. These results demonstrate that ProS is a pleiotropic anticoagulant with aPC-independent activities and highlight new roles for ProS in vascular development and homeostasis.
Subject(s)
Blood Coagulation Disorders/embryology , Blood Coagulation Disorders/physiopathology , Blood Vessels/embryology , Protein S Deficiency/embryology , Protein S Deficiency/physiopathology , Protein S/physiology , Animals , Blood Circulation , Blood Coagulation , Blood Coagulation Disorders/pathology , Blood Vessels/abnormalities , Blood Vessels/physiopathology , Brain/abnormalities , Brain/blood supply , Brain/embryology , Brain/pathology , Embryo Loss , Endothelial Cells/metabolism , Gene Targeting , Hemorrhage/embryology , Hemorrhage/metabolism , Hepatocytes/metabolism , Heterozygote , Homeostasis , Mice , Mice, Knockout , Protein C/metabolism , Protein S/genetics , Protein S/metabolism , Protein S Deficiency/pathology , Spinal Cord/blood supply , Spinal Cord/embryology , Thrombin/metabolismABSTRACT
PURPOSE OF REVIEW: Protein S has been one of the least mechanistically understood amongst the vitamin K-dependent coagulation proteins, and diagnosis of protein S deficiency and quantification of the associated thrombotic risk are not straightforward. In this review, the regulation of thrombin generation by protein S and the pathophysiological implications of protein S deficiency are discussed in the light of recent findings on the anticoagulant function(s) of protein S. RECENT FINDINGS: Protein S expresses both activated protein C-dependent and activated protein C-independent anticoagulant activities, but the former is generally believed to be lost upon binding of protein S to C4b-binding protein. Recently it has been shown that protein S acts as a cofactor of tissue factor pathway inhibitor in the down regulation of factor X-activation, which provides a mechanistic basis for the activated protein C-independent anticoagulant activity of protein S in plasma. In addition, reevaluation of the role of the protein S/C4b-binding protein complex has demonstrated that C4b-binding protein-bound protein S does express activated protein C-cofactor activity, especially during the inactivation of factor Va Leiden. SUMMARY: These findings underscore the central role of protein S in the regulation of coagulation and may have important implications for the evaluation of the thrombotic risk associated with protein S deficiency.
Subject(s)
Blood Coagulation , Protein S/physiology , Humans , Protein S Deficiency/physiopathology , Thrombin/metabolismABSTRACT
Protein S (PS) is an extensively studied protein with an important function in the down-regulation of thrombin generation. Because of the presence of a pseudogene and two different forms of PS in plasma, a bound and a free form, it is one of the most difficult thrombophilias to study. A deficiency of PS predisposes subjects to (recurrent) venous thromboembolism (VTE) and foetal loss. However, the conundrum of diagnosing PS deficiency has led to conflicting reports of PS as a risk factor for VTE. In this review, we aim to present a clinical perspective of PS deficiency.
Subject(s)
Blood Proteins/genetics , Pregnancy Complications, Hematologic/genetics , Protein S Deficiency/genetics , Protein S/metabolism , Venous Thromboembolism/etiology , Adult , Age of Onset , Anticoagulants/administration & dosage , Blood Coagulation Tests , Contraceptives, Oral, Hormonal , Contraindications , Estrogen Replacement Therapy , False Positive Reactions , Female , Heterozygote , Humans , Immunoassay , Infant, Newborn , Male , Middle Aged , Mutation , Polymerase Chain Reaction/methods , Pregnancy , Pregnancy Trimesters , Protein S/genetics , Protein S Deficiency/diagnosis , Protein S Deficiency/physiopathology , Recurrence , Risk Factors , Thrombophilia/genetics , Venous Thromboembolism/drug therapySubject(s)
Protein S Deficiency , Blood Coagulation/physiology , Blood Coagulation Factors/physiology , Enzyme Activation , Humans , Mutation , Protein C/physiology , Protein S/chemistry , Protein S/genetics , Protein S/physiology , Protein S Deficiency/blood , Protein S Deficiency/complications , Protein S Deficiency/genetics , Protein S Deficiency/physiopathology , Recurrence , Thromboembolism/etiology , Thrombophilia/geneticsABSTRACT
We report the case of a young Omani man, a regular blood donor, who presented twice in two months, with painful penile erection lasting more than 12 hours. The patient is known to have sickle cell trait [HbS 34.6%]. Although the first episode of penile erection settled with aspiration of blood and local injection of epinephrine, on the second occasion necessitated cavernosal glandular shunting. A subsequent investigation revealed a mild protein S deficiency. Although priapism is known to occur in sickle cell disease, it is unusual in sickle cell trait. Association of mild protein S deficiency with erythrocytosis could have precipitated the onset of priapism.
Subject(s)
Priapism/etiology , Protein S Deficiency/complications , Sickle Cell Trait/complications , Adult , Humans , Male , Priapism/diagnosis , Priapism/physiopathology , Protein S Deficiency/physiopathology , Recurrence , Sickle Cell Trait/physiopathologyABSTRACT
Hemorrhagic complications are common in patients with liver diseases and contribute to the morbidity and mortality associated to this condition. The liver plays a central role in the hemostatic process as here all clotting factors and their inhibitors are synthetized. Liver damage is commonly associated with variable impairment of hemostasis due to multiple causes: decreased synthesis of clotting and inhibitor factors, decreased clearance of activated factors, hyperfibrinolysis, accelerated intravascular coagulation, quantitative and qualitative platelet defects. Their clinical implications remain to be elucidated, so further studies addressing this issue are needed.
Subject(s)
Blood Coagulation Factors/biosynthesis , Hemostasis , Hemostatic Disorders/etiology , Liver Diseases/complications , Antithrombin III Deficiency/physiopathology , Disseminated Intravascular Coagulation/physiopathology , Fibrinolysis , Hemostatic Disorders/physiopathology , Heparin Cofactor II/deficiency , Humans , Liver Diseases/physiopathology , Protein C Deficiency/physiopathology , Protein S Deficiency/physiopathology , Serine Proteinase Inhibitors/deficiency , Thrombocytopenia/etiologyABSTRACT
A 27-year-old man, who was diagnosed as having familial protein S deficiency, developed deep vein thrombosis complicated with pulmonary thromboembolism. Anticoagulant therapy and thrombolytic therapy were commenced after the insertion of a temporary inferior vena cava filter (t-IVC-f). However, on day 5 after t-IVC-f insertion, IVC venography showed filter thrombosis. On day 13, we made a venotomy and removed the captured thrombi and inserted a permanent IVC-f. After removal of the t-IVC-f via the right brachial vein, thrombi that had not been seen earlier appeared in the right atrium (RA). It was suspected that the thrombi around the catheter had likely been stripped off during the catheter removal procedure. After the abdomen was closed, an extra operation was immediately performed. Under complete extracorporeal circulation, the RA was opened and the all thrombi were removed. The patient recovered well and was discharged on the 21st postoperative day without any complications.
Subject(s)
Protein S Deficiency/complications , Pulmonary Embolism/etiology , Venous Thrombosis/etiology , Adult , Heart Atria/surgery , Humans , Male , Protein S Deficiency/physiopathology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/physiopathology , Risk Factors , Venous Thrombosis/physiopathology , Venous Thrombosis/surgeryABSTRACT
Pulmonary hypertension in pregnancy is a rare condition but is associated with a high mortality. We report the case of a 29 year old female in early pregnancy with Protein C and S deficiency with recurrent deep venous thrombosis and pulmonary embolism and subsequent secondary pulmonary hypertension. The patient was counselled and consented for termination of pregnancy with tubal sterilization. She was administered continuous spinal anaesthesia with invasive monitoring. The successful anaesthetic management of this condition is described.
Subject(s)
Anesthesia, Spinal/methods , Hypertension, Pulmonary/etiology , Pregnancy Complications, Hematologic , Pulmonary Embolism/physiopathology , Sterilization, Tubal , Thrombophilia/physiopathology , Venous Thrombosis/physiopathology , Abortion, Therapeutic , Adult , Female , Humans , Pregnancy , Pregnancy Complications, Cardiovascular/etiology , Protein C Deficiency/physiopathology , Protein S Deficiency/physiopathology , Time FactorsABSTRACT
La mayoría de los ictus aparecen en personas de más de 50 años y asociados a factores de riesgo cardiovascular. Sin embargo, los ocurridos en pacientes jóvenes, no siempre se justifican con la arterioesclerosis, por lo que se buscan otras etiologías como las trombofilias. Los objetivos del estudio fueron 1.-Conocer la prevalencia de trombofilias y/o estados de hipercoagulabilidad en pacientes jóvenes ingresados por ictus en un hospital de tercer nivel. 2.-Conocer con qué frecuencia se realizan estudios de trombofilia en dichos pacientes. 3.-Cuáles son las características de este tipo de pacientes. Para ello se realizó un estudio descriptivo y retrospectivo, revisando las historias clínicas de todos los pacientes ingresados en el Hospital Clínico Universitario Lozano Blesa" (Zaragoza) durante el año 2004 con diagnóstico de ictus en paciente joven. Se registraron características, antecedentes de interés y estudios de trombofilia/s realizados. Se revisaron 64 pacientes, 32 de ellos fueron isquémicos. En 16 se solicitó algún tipo de estudio de trombofilia. En el estudio de trombofilia plasmática la alteración más frecuente fue el déficit de Antitrombina III, seguido de resistencia al factor V de Leiden. En el estudio de trombofilia genéticas la mutación de la Metiltetrahilrofolatorreductasa (IMTHFR), todos heterocigotos, fue el hallazgo más frecuente. Los parámetros estudiados en inmunología fueron variables e inconstantes. Conclusiones: 1.-Los estudios de trombofilias se solicitaron en menor número de lo que sería recomendable 2.-Las peticiones de estudio no son uniformes para los distintos tipos de trombofilias, siendo los estudios plasmáticos los más solicitados (AU)
Most ictus appear in people over 50 and are associated with cardiovascular risk factors. Nevertheless, those that occur in young patients are not always caused by arteriosclerosis, so other etiologies such as thrombophilias are sought. The objectives of this study were: 1.-To find out the prevalence of thrombophilias and/or states of hypercoagulation in young patients admitted for ictus in a tertiary hospital. 2.-To find out the frequency with which thrombophilia studies are carried out in such patients. 3.-To find out the characteristics of these patients. To do so, a descriptive and retrospective study was carried out, reviewing the clinical histories of all the patients admitted to the Hospital Cllnico Universitario "Lozano Blesa" (Zaragoza) during the year 2004 with diagnoses of ictus in young patients. The characteristics, interesting antecedents and thrombophilia studies carried out were recorded. 64 patients were reviewed, 32 of them showed ischemia. In 16, some type of thrombophilia study was requested. In the study of plasmatic thrombophilia, the most common alteration was antithrombin III deficiency, followed by resistance to V Leyden factor. In the study of genetic thrombophilias, the mutation of Metiltetrahifrofolato reductase (MTHFR), in all cases heterozygotic, was the most frequent finding. The parameters studied in immunology were variable. Conclusions: 1.- Thrombophilia studies are requested less frequently than would be recommendable 2.-The requests for studies are not uniform for the different types of trombofilias, plasmatic studies being the most requested (AU)
Subject(s)
Humans , Thrombophilia/diagnosis , Stroke/physiopathology , Antiphospholipid Syndrome/epidemiology , Activated Protein C Resistance/epidemiology , Protein C Deficiency/physiopathology , Antithrombin III Deficiency/physiopathology , Protein S Deficiency/physiopathology , Hyperhomocysteinemia/physiopathology , Prothrombin/geneticsABSTRACT
Protein S is a natural anticoagulant. Congenital protein S (PS) deficiency is a confirmed risk factor of venous thromboembolism (DVT) which though occurs infrequently yet is a leading cause of maternal mortality and morbidity. Congenital PS deficiency may also be responsible for obstetric complications such as preeclampsia/eclampsia, recurrent fetal loss and intrauterine fetal restriction. Congenital PS deficiency has been identified in 1-7.5% of patients with DVT and in 0.03-0.13% general Caucasian population. However, Japanese people have higher prevalence both in VTE patients (12.7%) and general population (0.48-0.63%). Because PS deficiency is the most frequent congenital thrombophilia in Japanese people, Japanese obstetricians must understand this thrombophilia and also that women with PS deficiency have an increased risk of VTE and a necessity of prophylactic use of anticoagulant against recurrent VTE during pregnancy and puerperium. This article reviews the literature to understand PS and congenital PS deficiency, especially the association of this thrombophilia with pregnancy.
Subject(s)
Protein S Deficiency/genetics , Protein S Deficiency/physiopathology , Thrombophilia/congenital , Adult , Animals , Blood Coagulation Disorders/genetics , Blood Coagulation Disorders/physiopathology , Delivery, Obstetric , Female , Humans , Infant, Newborn , Japan/epidemiology , Pregnancy , Pregnancy Complications, Hematologic/physiopathology , Protein S Deficiency/epidemiology , Thrombophilia/epidemiology , Thrombophilia/geneticsABSTRACT
OBJECTIVES: To review the state of the art relating to protein S deficiency as a risk factor for thrombosis and to make recommendations regarding the use of protein S measurements in the assessment of thrombotic risk in individual patients and families. DATA SOURCES, EXTRACTION, AND SYNTHESIS: Selection criteria were developed for the inclusion of publications from 1985 to 2001 based on the relevant literature concerned with the systematic review of diagnostic tests. Minimal selection criteria were agreed on and the articles stratified into level 1 if they met these criteria and level 2 if they did not meet these criteria. The included articles were reviewed by the authors and abstracted onto predetermined data collection forms. These forms were then scored and recommendations based on level 1 studies. As described elsewhere, results of discussions at the College of American Pathologists Conference XXXVI on Diagnostic Issues in Thrombophilia were used to revise the manuscript into its final form. CONCLUSIONS: Consensus was reached on 16 recommendations for the use of protein S assays in the assessment of thrombotic risk in individuals and families. Two themes run through the conclusions. First, protein S assays are the most technically problematic of the assays reviewed at this conference. Second, only 2 papers evaluating the diagnostic use of protein S assays met our level 1 inclusion criteria. These 2 problems point out the need for better standardized assays and rigorous studies of the diagnostic utility of these assays.