Diagnostic Blood Biomarkers for Acute Pulmonary Embolism: A Systematic Review.

(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional highly specific blood test could potentially lower the proportion of patients with suspected PE that require CTPA. The aim was to summarize the literature on the diagnostic performance of biomarkers of patients admitted to an emergency department with suspected acute PE. (2) Methods: Medline and Embase databases were searched from 1995 to the present. The study selection process, data extraction, and risk of bias assessment were conducted by two reviewers. Eligibility criteria accepted all blood biomarkers except D-dimer, and CTPA was used as the reference standard. Qualitative data synthesis was performed. (3) Results: Of the 8448 identified records, only 6 were included. Eight blood biomarkers were identified, of which, three were investigated in two separate studies. Red distribution width and mean platelet volume were reported to have a specificity of ≥ 90% in one study, although these findings were not confirmed by other studies. The majority of the studies contained a high risk of selection bias. (4) Conclusions: The modest findings and the uncertain validity of the included studies suggest that none of the biomarkers identified in this systematic review have the potential to improve the current diagnostic algorithm for acute PE by reducing the overuse of CTPA.

Abdominal obesity and the risk of venous thromboembolism among women: a potential role of interleukin-6.

BACKGROUND: Abdominal obesity increases the risk of venous thromboembolism (VTE). It remains unclear to what extent inflammation contributes to the risk of VTE from abdominal obesity. Our objectives were to investigate the association between abdominal obesity and VTE and the effect of inflammation on this association in a case-control study comprised of women. METHODS: We included 84 patients with VTE (18-60 years of age) and 100 controls. Waist circumference (WC), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) levels were determined at least 7 months after the thrombotic event. RESULTS: A total of 51 patients (61%) and 43 (43%) controls had abdominal obesity (WC ≥88 cm). The odds ratios (OR) adjusted for age were 2.40 [95% confidence interval (CI) 1.06-5.41; P=0.035] for a WC ≥88 cm compared to a WC <80 cm; the association was attenuated after adjusting for IL-6 (OR 1.86, 95% CI 0.80-4.33; P=0.149). For every 10-cm increment in WC, the risk of VTE adjusted for age increased by 1.38 (95% CI 1.08-1.77; P=0.010). The effect of an increased WC on the risk of VTE was again attenuated when IL-6 was entered in the regression model (OR 1.24, 95% CI 0.95-1.61; P=0.109). Risk estimates did not substantially change with adjustment for hsCRP. CONCLUSION: Our data indicate that the association between VTE and an increased WC was attenuated after adjustment for IL-6, suggesting a potential role of this interleukin in mediating the link between abdominal obesity and VTE.

Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A>G, PROC 2405C>T, THBD 1418C>T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05-3.00, p= 0.034) while women carrying the TFPI -287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26-0.83, p= 0.009). The TCC haplotype for TFPI T-33C/ TFPI T-287C/ TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23-0.90, p= 0.025). In conclusion, our data indicate that SERPINC1 786G>A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.

Autologous stem cell transplantation improves quality of life in economically challenged, Brazilian multiple myeloma patients.

OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in São Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post-treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS: Of the included patients, 87.8% had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t-tests confirmed a better outcome after autologous stem cell transplantation CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell transplantation in the quality of life of multiple myeloma patients in two public Brazilian institutions that provide assistance for economically challenged patients.

Performance of Platelin LS and dilute Russell's viper venom for the screening of lupus anticoagulant in patients with venous thromboembolism.

Lupus anticoagulant is associated with thrombosis and pregnancy morbidity, and its detection is of major clinical importance. The nature and concentration of phospholipids strongly influence the sensitivity of activated partial thromboplastin time (aPTT) reagents to lupus anticoagulant. We investigated the ability of Platelin LS, an aPTT reagent, to screen lupus anticoagulant among 94 patients with venous thromboembolism by comparing its performance with the dilute Russell viper venom time (dRVVT). Twenty-four patients had an abnormal aPTT and dRVVT, whereas 37 only had a prolonged dRVVT. In users of oral anticoagulants (n = 56), the dRVVT prolonged more frequently than the aPTT (98.2 vs 39.3%, P < 0.0001). After the mixing study, seven patients maintained abnormal aPTT and dRVVT ratios, five of whom had prolonged mixture with both tests. The agreement in the mixing study between aPTT and dRVVT was substantial (kappa = 0.78, 95% confidence interval = 0.48-1.00). Except for one patient, the aPTT screened all cases that demonstrated phospholipid dependency of their inhibitor during the confirmatory procedure with the dRVVT. In conclusion, the aPTT using Platelin LS was highly associated with the presence of lupus anticoagulant detected by the dRVVT among patients with venous thromboembolism, and could be reliably employed as a screening assay for lupus anticoagulant.

Cerebral venous thrombosis and hepatitis: case report / Trombose venosa cerebral e hepatite: relato de caso

Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been regarded as a rare associated condition. We report on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.

Dentre as várias causas infecciosas de trombose venosa cerebral (TVC), a hepatite viral tem sido reconhecida como causa rara de TVC. Relatamos sobre um homem de 56 anos com TVC associada a coinfecção pelos vírus B e C da hepatite, ressaltando possíveis mecanismos patogênicos. Sugerimos que sorologia para vírus da hepatite B e C deveria ser solicitado em todos os casos de TVC de origem indeterminada.

Cerebral venous thrombosis and hepatitis: case report.

Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been regarded as a rare associated condition. We report on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.

Avaliaçäo da prevalência de algumas causas de trombofilia hereditária e de hiperhomocisteinemia em pacientes com trombose venosa / Evaluation of prevalence of some cause of hereditary thrombophia and of hyperhomocysteinemia in patients with venous thrombosis

Alterações genéticas e adquiridas da hemostasia são responsáveis pelo estado de trombofilia caracterizado pela tendência a fenômenos tromboembólicos. As circunstâncias que fazem pensar em trombofilia são a ocorrência de trombose em indivíduos jovens, caráter recorrente da trombose, ocorrência em sítios não usuais e história familiar positiva. Defeitos hereditários e adquiridos da hemostasia ou a interação de ambos podem ser causas de trombofilia, Muitas vezes estes defeitos estão associados a fatores de risco desencadeadores, como o uso de estrogênio e progestagênio, cirurgia, gestação e puerpério. Com o intuito de avaliar algumas causas de trombofilia realizamos um estudo de caso-controle na Universidade Federal de São Paulo - Escola Paulista de Medicina. O estudo envolveu 94 pacientes com trombose venosa sem causa aparente e 136 indivíduos controles, selecionados durante o período de julho de 1996 a dezembro de 1999. Avaliamos a prevalência das deficiências dos inibidores da coagulação, desfrinogenemia, fator V de Leiden, mutação da protrombina, MTHFR C677T e hiperhomocisteinemia nos pacientes. Comparamos a freqüência do fator V de Leiden, mutação da protrombina, MTHFR C677T, hiperhomocisteinemia e grupo sangüíneo ABO em pacientes e em indivíduos normais. Analisamos também alguns dados clínicos e epidemiológicos dos pacientes. Dentre os 94 pacientes havia 37 (39 por cento) casos de recorrência, sendo que 65 por cento das recorrências foram observadas no período de 3 anos após o primeiro episódio. Houve 149 episódios de trombose venosa, dos quais 45 por cento estiveram associados a pelo menos um fator de risco desencadeador. Entre as mulheres o fator de risco mais freqüente foi o uso de estrogênio e progestagênio, e em quase a metade dos casos a trombose ocorreu nos primeiros 8 meses após a introduçäo da hormonioterapia. No grupo de pacientes a deficiência de A TIII foi encontrada em 4 casos (4,3 por cento), a deficiência de proteína C em 1 paciente(1,7 por cento) entre 58 avaliados, a deficiência de PS ocorreu em 7 casos (13,5 por cento) entre 52 avaliados e nenhum paciente tinha desfibrinogenemia. O fator V de Leiden esteve presente em 6 pacientes (6,4 por cento) e 3 indivíduos controles(2,2 por cento) e o odds ratio para trombose venosa foi de 1,95(IC95 por cento 0,43; 8,78). A mutaçäo da protrombina ocorreu em 8 pacientes(8,5 por cento) e 1 controle(0,7 por cento), com um odds ratio de 12,36 (IC95 por cento 1,46; 104,48). Quatro destes...(au)