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1.
Vasc Health Risk Manag ; 16: 53-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021228

RESUMO

Introduction: Factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR (C677T) gene mutations were investigated in many studies for their association with Deep Venous Thrombosis. Case Presentation: A North Lebanese family has been examined, from an index case, a 40-year-old woman, who had a history of venous thrombosis with unexplained recurrent miscarriage. The index case was found to be heterozygous for factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T gene variants. Her family members were heterozygous for at least two of the three-point mutations, and multiple risk factors associated with thrombophilia were identified. Conclusion: Our findings emphasize the need for clarifying the utility and futility of thrombophilia testing in the era of molecular diagnostics.


Assuntos
Aborto Habitual/etiologia , Resistência à Proteína C Ativada/genética , Coagulação Sanguínea/genética , Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Protrombina/genética , Trombofilia/genética , Trombose Venosa/etiologia , Aborto Habitual/sangue , Aborto Habitual/diagnóstico , Resistência à Proteína C Ativada/sangue , Resistência à Proteína C Ativada/complicações , Resistência à Proteína C Ativada/diagnóstico , Adulto , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Líbano , Linhagem , Fenótipo , Gravidez , Fatores de Risco , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/diagnóstico , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
2.
Res Vet Sci ; 127: 122-129, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704497

RESUMO

Gram positive bacteria are a cause of sepsis in human preterm infants, and associates with high mortality and hemostatic dysfunction. It is unknown whether bovine colostrum may protect against sepsis and prevent hemostatic dysfunction. The current study was part of an overall sepsis study investigating Staphylococcus epidermidis (SE) induced sepsis in premature pigs including investigation of the effect of feeding bovine colostrum. The specific hypothesis of this study was that the hemostatic response would be hypercoagulable in septic pigs compared to non-infected controls, and that feeding bovine colostrum would increase the hypercoagulant response. Thromboelastography, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were characterized in SE infected pigs, SE infected pigs fed bovine colostrum, and uninfected controls. All pigs were followed for 24 h. In addition, the same parameters were evaluated in a group of premature pigs and a group of full born pigs all followed for 11 days. SE septic premature pigs were characterized by increased clot strength and decreased fibrinolysis, significantly low platelet count and high fibrinogen concentration. Feeding bovine colostrum did not affect the hemostatic response. Compared to full born pigs, preterm newborn pigs demonstrated reduced clot strength, prolonged prothrombin time and low fibrinogen concentration. In all pigs, the fibrinogen concentration increased 11 days post-partum. To conclude, SE induced sepsis in premature pigs resulted in hypercoagulability. Bovine colostrum did not mitigate the hemostatic response. A hypocoagulable hemostatic response was present in healthy preterm pigs compared to full born pigs, similar to previous reports in infants.


Assuntos
Colostro/fisiologia , Nascimento Prematuro/veterinária , Sepse/veterinária , Infecções Estafilocócicas/veterinária , Staphylococcus epidermidis/fisiologia , Doenças dos Suínos/sangue , Trombofilia/veterinária , Animais , Bovinos , Feminino , Gravidez , Sepse/sangue , Infecções Estafilocócicas/sangue , Suínos , Trombofilia/sangue
3.
Biomed Res Int ; 2019: 8787010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534965

RESUMO

Uterine radial artery resistance index (URa-RI) by Doppler ultrasound may reflect the changes in the uteroplacental circulation and be associated with adverse events in early pregnancy. Recurrent pregnancy losses (RPL) are associated with thrombophilia, and anticoagulation treatment with low molecular weight heparin improves pregnancy outcome in women with RPL and thrombophilia. A retrospective cohort study was conducted in 139 pregnant women with 3 or more RPL and thrombophilia. The relationship between pregnancy outcome and dynamic changes of URa-RI was analyzed in 116 women who delivered a liveborn infant and 23 who miscarried the index pregnancy. Patients were on preconception low molecular weight heparin, low-dose aspirin (81mg per day), and prednisone treatment. URa-RI was measured during periovulation time, at the time of positive pregnancy test, and then repeated every two weeks until 32-week gestation or the time of miscarriage. The URa-RI at 8-week gestation was significantly higher in women who miscarried the index pregnancy than those who delivered alive born infant (0.51±0.08 vs. 0.42±0.03, P<0.001). Receiver operating characteristic curve analysis demonstrated that URa-RI of 8 wk gestation effectively distinguished women who miscarried from those who had a live birth with an area under the curve of 82.6% (95% CI 69.01-97.17). After adjusting for covariates including age, BMI, and number of miscarriages, multiple logistic regression models showed that each 0.1 unit increase of URa-RI of 8 wk gestation was associated with 18.70-point increase in the risk of miscarriage (OR19.70, 95%CI 4.26-91.1, P<0.001), and women with an URa-RI≥0.45 had an OR of 49.48 (95% CI 8.01-307.95; P<0.001) for miscarriage compared to those who had URa-RI<0.45. In women with RPL and inherited thrombophilia, increased URa-RI at 8-week gestation was associated with spontaneous abortion independent of other risk factors while they were on anticoagulation treatment.


Assuntos
Aborto Habitual , Complicações Hematológicas na Gravidez , Trombofilia , Ultrassonografia Doppler Dupla , Artéria Uterina , Resistência Vascular , Aborto Habitual/sangue , Aborto Habitual/diagnóstico por imagem , Aborto Habitual/tratamento farmacológico , Aborto Habitual/fisiopatologia , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Feminino , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Nascimento Vivo , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico por imagem , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/fisiopatologia , Estudos Retrospectivos , Trombofilia/sangue , Trombofilia/diagnóstico por imagem , Trombofilia/tratamento farmacológico , Trombofilia/fisiopatologia , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/fisiopatologia
4.
Ann Hematol ; 98(11): 2533-2539, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31552445

RESUMO

Patients with polycythemia vera (PV) have a high incidence of thrombotic events (TEs), contributing to a greater mortality risk than the general population. The relationship between hematocrit (HCT) levels and TE occurrence among patients with PV from the Veterans Health Administration (VHA) was evaluated to replicate findings of the CYTO-PV trial with a real-world patient population. This retrospective study used VHA medical record and claims data from the first claim with a PV diagnosis (index) until death, disenrollment, or end of study, collected between October 1, 2005, and September 30, 2012. Patients were aged ≥ 18 years at index, had ≥ 2 claims for PV (ICD-9-CM code, 238.4) ≥ 30 days apart during the identification period, continuous health plan enrollment from 12 months pre-index until end of study, and ≥ 3 HCT measurements per year during follow-up. This analysis focused on patients with no pre-index TE, and with all HCT values either < 45% or ≥ 45% during the follow-up period. The difference in TE risk between HCT groups was assessed using unadjusted Cox regression models based on time to first TE. Patients (N = 213) were mean (SD) age 68.9 (11.5) years, 98.6% male, and 61.5% white. TE rates for patients with HCT values < 45% versus ≥ 45% were 40.3% and 54.2%, respectively. Among patients with ≥ 1 HCT before TE, TE risk hazard ratio was 1.61 (95% CI, 1.03-2.51; P = 0.036). This analysis of the VHA population further supports effective monitoring and control of HCT levels < 45% to reduce TE risk in patients with PV.


Assuntos
Hematócrito , Policitemia Vera/sangue , Trombose/etiologia , Adulto , Idoso , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia Vera/complicações , Estudos Retrospectivos , Risco , Trombofilia/sangue , Trombofilia/etiologia , Trombose/epidemiologia , Estados Unidos/epidemiologia , Veteranos
5.
Clin Adv Hematol Oncol ; 17(7): 396-404, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31449506

RESUMO

Venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism, is one of the leading causes of non-obstetric maternal death in the United States. Physiologic and anatomic changes associated with pregnancy set the stage for a hypercoagulable state. In addition, other risk factors-including those associated with certain fetal characteristics such as low birth weight or stillbirth-have been correlated with an increased risk for VTE. Women with a personal or strong family history of VTE, as well as documented thrombophilia, represent a unique group in whom antepartum and/or postpartum prophylaxis can be considered. The choice of anticoagulant therapy for either treatment or prophylaxis in most cases is heparin, most commonly low-molecular-weight heparin. This is owing to the fact that vitamin K antagonists and the direct oral anticoagulants are contraindicated in pregnancy because of potential teratogenicity. With careful management and vigilant monitoring, appropriate anticoagulation can be used safely and effectively to improve patient outcomes.


Assuntos
Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Administração Oral , Feminino , Humanos , Gravidez , Complicações Hematológicas na Gravidez/sangue , Embolia Pulmonar/sangue , Fatores de Risco , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Tromboembolia Venosa/sangue , Trombose Venosa/sangue
6.
Clin Respir J ; 13(8): 530-537, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295762

RESUMO

OBJECTIVE: The aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) in protein C (PROC) and protein S (PROS1) genes with deep venous thrombosis (DVT) in a thrombophilia family. METHODS: DNA were extracted from blood of participants. Five PROC SNPs and 11 PROS1 SNPs were selected from the Hapmap and 1000 Genomes databases. The minor allele frequencies (MAFs) of SNPs in the thrombophilia family (Group I) and healthy controls (Group II) were detected. SNPs were analysed by Chi-square, logistic regression and linkage disequilibrium patterns. RESULTS: MAFs for all 16 SNPs were greater than 0.05. Chi-square analysis showed significant differences between Group I and Group II in the frequency of mutant alleles of rs1799808, rs5936, rs6123, rs12634349, rs6441600 and rs13062355 SNPs (P < .05). Logistic regression analysis found that mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT in this family (OR > 1, L95 > 1). Linkage disequilibrium was found among 15 of the PROC and PROS SNPs. CONCLUSIONS: Single nucleotide polymorphisms (SNPs) of PROC and PROS1 may be closely associated with DVT in this thrombophilia family. Mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT, whereas mutant alleles of rs1799810, rs6123 and rs12634349 may protect individuals from DVT. With the exception of rs9681204, there was linkage disequilibrium between PROC and PROS1 SNPs. We found that 12 haplotypes were in linkage disequilibrium, but linkage disequilibrium was strong in only eight of these (frequency >5%).


Assuntos
Polimorfismo de Nucleotídeo Único/genética , Proteína C/genética , Proteína S/genética , Trombofilia/genética , Trombose Venosa/genética , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Proteínas de Ligação ao Cálcio , Criança , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Mutação , Trombofilia/sangue , Trombose Venosa/epidemiologia , Adulto Jovem
7.
J Stroke Cerebrovasc Dis ; 28(7): e92-e94, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31097325

RESUMO

Amaurosis fugax (AmF) is defined as transient monocular visual loss secondary to retinal ischemia. In most patients presenting with AmF, the attack of visual loss occurs in the same eye. A 64-year-old woman experienced transient visual loss in her right eye. Three days after that, an attack happened on the left side. In total, she had 5 episodes of AmF in 2 months. AmF occurred on both sides at different times, and so may be referred to as "Alternating AmF". Diffusion-weighted magnetic resonance imaging showed high-intensity lesions in various parts of brain, and laboratory examination revealed elevated D-dimer and ovarian tumor marker. We suspected Trousseau syndrome and found a giant ovary tumor. After removal of the tumor, no recurrence was observed. When a patient with alternating AmF is encountered, screening for malignancy is essential.


Assuntos
Adenocarcinoma de Células Claras/complicações , Amaurose Fugaz/etiologia , Neoplasias Ovarianas/complicações , Tromboembolia/etiologia , Trombofilia/etiologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/terapia , Amaurose Fugaz/diagnóstico por imagem , Biomarcadores Tumorais/sangue , Coagulação Sanguínea , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Recidiva , Síndrome , Tromboembolia/sangue , Tromboembolia/diagnóstico por imagem , Trombofilia/sangue , Trombofilia/diagnóstico , Resultado do Tratamento
8.
J Cancer Res Clin Oncol ; 145(7): 1695-1707, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31020419

RESUMO

BACKGROUND: Hypercoagulability is a major cancer-associated complication linked to poor patient prognosis. The production of neutrophil extracellular traps (NETs) is increasingly found to be linked with the development and metastasis of cancer, as well as with thrombi formation in cancer patients. We hypothesized that the neutrophil NET release may be triggered by specific cytokines in oral squamous cell carcinoma (OSCC) patients, thereby predisposing them to a hypercoagulable state. Moreover, we have evaluated the interaction between NETs and endothelial cells (ECs). METHODS: NET procoagulant activity was assessed based on fibrin and purified coagulation complex production assays, as well as by measuring coagulation time (CT). We further used confocal microscopy to quantify the exposure of phosphatidylserine (PS), fibrin strands, and cell FVa/Xa binding. RESULTS: OSCC patients with stage III/IV exhibited elevated plasma NET levels compared to stage I/II or CTR (all P < 0.05). Neutrophils from OSCC patients are predisposed to amplified NET release compared to those from CTR. Furthermore, depleting IL-8, IL-6, and TNF-α led to a reduction in NET release in the plasma. OSCC NETs increased thrombin and fibrin generation and decreased CT significantly (P < 0.05). When NETs were isolated and used to treat ECs, these cells exhibited disrupted morphology by retracting from their cell-cell junctions and convert to a procoagulant phenotype. These effects could be attenuated by approximately 70% using DNase I. CONCLUSIONS: Our findings are consistent with a model wherein OSCC drives a systemic inflammatory state, which, in turn, drives neutrophils to prime and release NETs, which drive the development of a hypercoagulable state. Intervening in this process may be a viable means of disrupting these undesirable coagulation dynamics in stage III/IV OSCC patients.


Assuntos
Armadilhas Extracelulares/metabolismo , Neoplasias Bucais/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Trombofilia/sangue , Citocinas/sangue , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Neutrófilos/metabolismo , Neutrófilos/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Trombofilia/patologia
9.
Acta Haematol ; 142(2): 113-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30995655

RESUMO

BACKGROUND/AIMS: Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) have been described as markers of endothelial damage and dysfunction in several diseases, including deep venous thrombosis. Their role in patients with known thrombophilia has not yet been evaluated. Both EPCs and CECs represent extremely rare cell populations. Therefore, it is essential to use standardized methods for their identification and quantification. METHODS: In this study, we used multicolor flow cytometry to analyze the number of EPCs and CECs in patients with thrombophilia with or without a history of thrombosis. Patients with hematological malignancies after high-dose chemotherapy and patients with acute myocardial infarction were used as positive controls. RESULTS: EPC and CEC immunophenotypes were determined as CD45dim/-CD34+CD146+CD133+ and CD45dim/-CD34+CD146+CD133-, respectively. Increased levels of endothelial cells were observed in positive control groups. No significant changes in the number of EPCs or CECs were detected in patients with thrombophilia compared to healthy controls. CONCLUSION: Our optimized multicolor flow cytometry method allows unambiguous identification and quantification of endothelial cells in the peripheral blood. Our results support previous studies showing that elevated levels of CECs could serve as an indicator of endothelial injury or dysfunction. Normal levels of CECs or EPCs were found in patients with thrombophilia.


Assuntos
Antígenos CD/sangue , Células Endoteliais , Células Progenitoras Endoteliais , Citometria de Fluxo , Trombofilia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombofilia/sangue , Trombofilia/patologia
10.
Gastroenterology ; 157(1): 34-43.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986390

RESUMO

DESCRIPTION: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. METHODS: This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. BEST PRACTICE ADVICE 1: Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. BEST PRACTICE ADVICE 2: In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction-induced coagulation abnormalities. BEST PRACTICE ADVICE 3: Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. BEST PRACTICE ADVICE 4: The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. BEST PRACTICE ADVICE 5: Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. BEST PRACTICE ADVICE 6: The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. BEST PRACTICE ADVICE 7: The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. BEST PRACTICE ADVICE 8: Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. BEST PRACTICE ADVICE 9: Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. BEST PRACTICE ADVICE 10: Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). BEST PRACTICE ADVICE 11: Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. BEST PRACTICE ADVICE 12: Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue/métodos , Cirrose Hepática/sangue , Trombofilia/terapia , Trombose Venosa/terapia , Anticoagulantes/uso terapêutico , Antifibrinolíticos/uso terapêutico , Antitrombinas/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Fibrinogênio/metabolismo , Hematócrito , Heparina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Cirrose Hepática/complicações , Plasma , Contagem de Plaquetas , Veia Porta , Tromboelastografia , Trombocitopenia , Trombofilia/sangue , Trombofilia/complicações , Trombopoetina/agonistas , Reação Transfusional , Trombose Venosa/sangue , Trombose Venosa/complicações
11.
Clin Appl Thromb Hemost ; 25: 1076029619841700, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968703

RESUMO

The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.


Assuntos
Transtornos Plaquetários/sangue , Trombofilia/sangue , Trombose Venosa/sangue , Adulto , Transtornos Plaquetários/epidemiologia , Transtornos Plaquetários/etnologia , Feminino , Humanos , Masculino , México/epidemiologia , México/etnologia , Estudos Retrospectivos , Síndrome , Trombofilia/epidemiologia , Trombofilia/etnologia , Trombose Venosa/epidemiologia , Trombose Venosa/etnologia
12.
Am J Ther ; 26(3): e364-e374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30985485

RESUMO

BACKGROUND: Inherited (hereditary) thrombophilia is a genetic disorder that affects coagulation, being responsible for more than 60% of idiopathic (spontaneous or unprovoked) thromboembolic events. Association of inherited thrombophilia with pregnancy increases the risk of thromboembolic disease, and it may be related to many complications, such as preeclampsia, recurrent miscarriage intrauterine growth restriction, early detachment of placenta, and prematurity. AREAS OF UNCERTAINTY: Interpretation of a positive test for thrombophilia in pregnant women is difficult because they have many natural changes in the coagulation system. Genetic diagnosis of thrombophilia, after a thrombotic event or during a pregnancy complication, has a major importance, not only to define its etiology but also to determine the duration of anticoagulant treatment and risk stratification for prophylaxis treatment. DATA SOURCES: Literature search was performed using electronic database (PubMed) between April 1981 and November 2018. We used different keywords and MeSH terms to generate the most relevant results related to the inherited thrombophilia and its impact on pregnancy. RESULTS: Screening for inherited thrombophilia in young women is recommended in case of personal history of venous thromboembolism, first-degree relatives with a history of high-risk thrombophilia, or personal history of second-trimester miscarriage. Decision to recommend thromboprophylaxis with anticoagulant treatment in pregnant women with inherited thrombophilia is determined by history of venous thromboembolism, type and associated risk of inherited thrombophilia, and presence of additional risk factors. Low-molecular-weight heparins are the preferred agents for prophylaxis in pregnancy, while the doses vary depending on thrombophilia type, personal history, and associated risk factors. CONCLUSIONS: Association between 2 procoagulant conditions, inherited thrombophilia and pregnancy, has an important impact for the mother and fetus. This review will summarize the impact of each inherited prothrombotic factor on cardiovascular and pregnancy outcomes and will discuss the role of anticoagulation treatment for women diagnosed with inherited thrombophilia.


Assuntos
Anticoagulantes/uso terapêutico , Complicações na Gravidez/prevenção & controle , Trombofilia/complicações , Tromboembolia Venosa/prevenção & controle , Aborto Habitual/etiologia , Aborto Habitual/prevenção & controle , Feminino , Humanos , Período Periparto/sangue , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/prevenção & controle , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Fatores de Risco , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
13.
BMC Cardiovasc Disord ; 19(1): 55, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845907

RESUMO

BACKGROUND: We aimed to investigate the role of hypercoagulability on the risk of lifetime cardiovascular recurrences after myocardial infarction or ischaemic stroke. METHODS: Young women (< 50 years) with either myocardial infarction (n = 197) or ischaemic stroke (n = 107) were followed between 1995 and 2012 in the RATIO follow-up study. To determine whether hypercoagulability affects the risk or recurrence, a coagulation score based on acquired and inherited markers was compiled and used in a quartile analysis. Hazard ratios (HRs) obtained from Cox proportional models and adjusted for several cardiovascular risk factors were used to compare quartiles of the coagulation score for the risk of recurrence. RESULTS: During a median follow-up of 19 years, 59 cardiovascular recurrences occurred. In patients with myocardial infarction no association was found between a high prothrombotic score and recurrences (highest quartile vs lowest quartile HR 0.7, 95% CI, 0.3-1.8). Conversely, ischaemic stroke patients with a high prothrombotic score showed a doubling in risk of long-term cardiovascular recurrences (HR 1.9, 95% CI 0.6-6.3) compared with ischaemic stroke patients and low levels of the score, with a dose response relationship. CONCLUSIONS: An increased coagulation tendency might be associated with long-term cardiovascular risk in women with ischaemic stroke, but not in women with myocardial infarction.


Assuntos
Coagulação Sanguínea , Isquemia Encefálica/epidemiologia , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Trombofilia/epidemiologia , Adolescente , Adulto , Fatores Etários , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Países Baixos/epidemiologia , Prognóstico , Recidiva , Medição de Risco , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Trombofilia/sangue , Trombofilia/diagnóstico , Fatores de Tempo , Adulto Jovem
14.
Methods Mol Biol ; 1955: 275-286, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868535

RESUMO

The most severe clinical symptomatology of Chagas disease affects ~30% of those chronically infected with the Trypanosoma cruzi parasite. The pathogenic mechanisms that lead to life-threatening heart and gut tissue disruptions occur "silently" for a longtime in a majority of cases. As a result, despite there are several serological and molecular methods available to diagnose the infection in its acute and chronic stages, diagnosis is often achieved only after the onset of clinical symptoms in the chronic phase of the disease. Furthermore, although there are two drugs to treat it, the assessment of their performance is impractical with current parasite-derived diagnostics, and therapeutic efficacy cannot be acknowledged in a timely manner.In this chapter we present two procedures to measure host-derived molecules as surrogates of therapeutic response against chronic T. cruzi infection. Their outputs relate to the generation and activity of thrombin, a major component of the blood coagulation cascade. This is due to the fact that a hypercoagulability state has been described to occur in chronic Chagas disease patients and revert after treatment with benznidazole.


Assuntos
Doença de Chagas/sangue , Trombina/análise , Trombofilia/sangue , Biomarcadores/sangue , Doença de Chagas/complicações , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Doença Crônica , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Nitroimidazóis/uso terapêutico , Prognóstico , Trombofilia/complicações , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos
15.
Thromb Res ; 176: 11-17, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763822

RESUMO

INTRODUCTION: Patients with hereditary spherocytosis (HS) are characterized by having an increased risk for thrombosis. An early manifestation of thrombotic complications can occur even in childhood, especially after surgery. Hypercoagulability can be associated with hemolytic crises. AIM: The aim of this study was to investigate the hemostatic state in children with HS using global hemostasis assays. METHODS: The hemostatic status of 62 children (38 boys and 24 girls; age range: 0.5 to 17 years) with HS during and without hemolytic crisis was assessed using clotting times (APTT, TT, and PR), fibrinogen and D-dimer levels, and global hemostasis, thromboelastography (TEG) and thrombodynamics (TD) assays. One hundred and two healthy children undergoing annual medical examination were enrolled as a control group. RESULTS: TEG and TD parameters were increased in the children with HS compared to the control group (60 ±â€¯5 mm vs. 53 ±â€¯4 mm, p < 0.05 for TEG maximum amplitude; 28 ±â€¯3 µm/min vs. 24 ±â€¯2 µm/min, p < 0.05 for TD clot growth rate), while APTT, TT and PR were not significantly different between the two groups. Patients with HS were divided into 2 groups: those during hemolytic crisis (28 patients) and those without hemolytic crisis (34 patients). TEG and TD parameters were increased in those during hemolytic crisis compared to the steady state HS group (62 ±â€¯5 mm vs. 57 ±â€¯4 mm, p < 0.05 for TEG maximum amplitude; 31 ±â€¯4 µm/min vs. 26 ±â€¯3 µm/min, p < 0.05 for TD clot growth rate). The D-dimer levels were increased in 4 HS patients, for whom the activation of blood clotting was noted. Fibrinogen levels were decreased in patients with HS compared to the control group (2.1 ±â€¯0.4 mg/ml vs. 2.6 ±â€¯0.4 mg/ml, p < 0.05). Other tests were within the reference ranges for both groups. CONCLUSIONS: The global hemostasis tests TEG and TD revealed hypercoagulability in patients with HS. More dramatic changes were observed in patients experiencing a hemolytic crisis.


Assuntos
Hemostasia , Esferocitose Hereditária/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Lactente , Masculino , Tromboelastografia , Trombofilia/sangue
16.
Pathology ; 51(3): 292-300, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30665674

RESUMO

We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.


Assuntos
Anticoagulantes/farmacologia , Síndrome Antifosfolipídica/diagnóstico , Testes de Coagulação Sanguínea , Coagulação Sanguínea/efeitos dos fármacos , Inibidor de Coagulação do Lúpus/análise , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Tempo de Protrombina , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Trombofilia/sangue , Trombofilia/tratamento farmacológico
17.
J Stroke Cerebrovasc Dis ; 28(4): 882-889, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30595511

RESUMO

OBJECTIVE: We evaluated the ability of genetic and serological testing to diagnose clinically relevant thrombophilias in young adults with ischemic stroke. METHODS: We performed a retrospective cohort study of patients aged 18-65 years diagnosed with acute ischemic stroke at a comprehensive stroke center between 2011 and 2015 with laboratory testing for thrombophilia. The primary outcome was any positive thrombophilia screening test. The secondary outcome was a change in clinical management based on thrombophilia testing results. Logistic regression was used to assess whether the prespecified risk factors of age, sex, prior venous thromboembolism, family history of stroke, stroke subtype, and presence of patent foramen ovale were associated with outcomes. RESULTS: Among 196 young ischemic stroke patients, at least 1 positive thrombophilia test was identified in 85 patients (43%; 95% CI, 36%-51%) and 16 (8%; 95% CI, 5%-13%) had a resultant change in management. Among 111 patients with cryptogenic strokes, 49 (44%) had an abnormal thrombophilia test and 9 (8%) had a change in management. After excluding cases of isolated hyperhomocysteinemia or methylenetetrahydrofolate reductase or Factor V Leiden gene mutation heterozygosity, the proportion of patients with an abnormal thrombophilia screen decreased to 24%. Prespecified risk factors were not significantly associated with positive thrombophilia testing or a change in management. CONCLUSIONS: Two-of-five young patients with ischemic stroke who underwent thrombophilia screening at our institution had at least 1 positive test but only one-in-twelve had a resultant change in clinical management. Neither cryptogenic stroke subtype nor other studied clinical factors were associated with a prothrombotic state.


Assuntos
Testes de Coagulação Sanguínea , Coagulação Sanguínea , Isquemia Encefálica/etiologia , Tomada de Decisão Clínica , Análise Mutacional de DNA , Testes Sorológicos , Acidente Vascular Cerebral/etiologia , Trombofilia/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Autoanticorpos/sangue , Biomarcadores/sangue , Coagulação Sanguínea/genética , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/genética , Adulto Jovem
18.
Cartilage ; 10(1): 53-60, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29308659

RESUMO

OBJECTIVE: To test whether patients with spontaneous osteonecrosis of the knee (SONK) are characterized by abnormal levels of thrombophilia-associated factors. DESIGN: Twenty-five patients with SONK were recruited. Inclusion criteria were (1) age >40 years, (2) acute onset knee pain not precipitated by trauma, and (3) MRI findings consistent with SONK. Exclusion criteria were (1) history of cancer and chemotherapy and (2) factors associated with secondary osteonecrosis. Blood tests included 13 thrombophilia-associated factors that were either heritable mutations or acquired factors. Descriptive statistics included medians, ranges, means, and standard deviations. Mann-Whitney test was used to compare thrombophilia-associated factor levels between the sexes. Spearman's rank test was used to test correlations between smoking status and each thrombophilia-associated factor. Level of significance was set at 0.05. RESULTS: Median patient age was 62 years (range, 44-77 years). There were 16 (64%) men. Thirteen (52%) patients had thrombophilia-associated factor abnormalities of which 9 were elevated fibrinogen but this was less than 1 standard deviation above norm threshold. Other findings were 3 patients with marginally decreased antithrombin below norm threshold, low protein S Ag in only 1 patient, and factor V Leiden mutation heterozygosity in 2 patients, which was not higher than normal population prevalence. Thrombophilia-associated factors neither differed between sexes ( P = nonsignificant) nor correlated with smoking status ( P = nonsignificant). CONCLUSION: Thrombophilia-associated factor abnormalities in patients with SONK were minimal. Therefore, clinical workup and treatment strategy in this disease should focus on addressing alternative etiologies leading to abnormal subchondral bone metabolism with focal osteopenia.


Assuntos
Fator V/análise , Osteonecrose/sangue , Trombofilia/complicações , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteonecrose/etiologia , Osteonecrose/patologia , Fatores de Risco , Trombofilia/sangue , Trombofilia/patologia
19.
Burns ; 45(1): 54-62, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30327230

RESUMO

BACKGROUND: Severe burns can induce a hypercoagulable state which is not depicted in conventional coagulation assays. The thrombin generation assay allows global assessment of coagulation and can identify hypercoagulability. We report changes in thrombin generation in patients after severe burn injury. METHODS: We measured TGA, rotational thrombelastometry and conventional assays in 20 consecutive patients with a total body surface area burned of >20% over a 2-week period: the day after burn trauma (A), the morning after surgical excision of burn wounds (B) and on post-admission days 7 (C) and 14 (D). RESULTS: Thrombin generation assay showed a procoagulatory state: there was an increase in the velocity of thrombin generation (increase in time to peak of +13%, increase in velocity index of +22%), and peak amount of thrombin (+25%) between days A and B. All parameters reached their highest levels on day C and returned towards normal on day D. Rotational thrombelastometry showed a hypercoagulable state with an increase in clot firmness and alpha angle. Conventional coagulation tests remained within reference values. CONCLUSIONS: In the first two weeks following burn, both the thrombin generation assay and rotational thrombelastometry show a hypercoagulable state, while conventional coagulation tests remain normal.


Assuntos
Testes de Coagulação Sanguínea , Queimaduras/sangue , Trombina/metabolismo , Trombofilia/sangue , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Testes Imediatos , Estudos Prospectivos , Tempo de Protrombina , Tromboelastografia , Trombofilia/diagnóstico
20.
Phlebology ; 34(5): 324-335, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30282515

RESUMO

INTRODUCTION: Deep vein thrombosis is a multifactorial disease with many acquired and genetic risk factors. Polymorphism in the APOE gene is an upcoming potential pathogenic factor whose role is unclear in deep vein thrombosis. METHODS: An equal number of deep vein thrombosis cases and controls (N = 100, each) were investigated for APOE gene polymorphisms along with known acquired and hereditable thrombophilic risk factors. APOE genotyping was done by polymerase chain reaction. RESULTS: The ε3/ε4 and ε2/ε3 APOE genotypes were commoner in deep vein thrombosis cases than controls but not statistically significant ( ε3/ε4 → 18% versus 11%, OR = 1.776, CI = 0.792-3.984, p = 0.16; ε2/ε3 →10% versus 9%, OR = 1.123, CI = 0.436-2.895, p = 0.809). However, the following risk factors were found to be laterally associated with APOE genotypes in cases of deep vein thrombosis: pregnancy with ε2/ε3 genotype positivity (N = 29; p = 0.019), recurrent pregnancy loss with ε3/ε3 genotype (N = 29; p = 0.016), normal antithrombin levels with ε3/ε3 genotype (N = 62; p = 0.03) and non-O blood group with ε3/ε4 genotype (N = 100; p = 0.023). CONCLUSION: APOE genotypes have shown only a modest association with deep vein thrombosis and were not statistically significant. A lateral association of these genotypes with thrombophilic risk factors was observed which may be investigated further for the possible pathogenetic mechanisms and their therapeutic implications.


Assuntos
Apolipoproteínas E/genética , Polimorfismo de Nucleotídeo Único , Trombofilia/genética , Trombose Venosa/genética , Adolescente , Adulto , Idoso , Apolipoproteínas E/sangue , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Trombofilia/sangue , Trombose Venosa/sangue
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