Apixaban versus Enoxaparin for Thromboprophylaxis after Hip Replacement

BACKGROUND There are various regimens for thromboprophylaxis after hip replacement. Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree. Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use. METHODS In this double-blind, double-dummy study, we randomly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours. Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound; enoxaparin therapy was initiated 12 hours before surgery. Prophylaxis was continued for 35 days after surgery, followed by bilateral venographic studies. The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause during the treatment period. Patients were followed for an additional 60 days after the last intended dose of study medication. RESULTS A total of 1949 patients in the apixaban group (72.0%) and 1917 patients in the enoxaparin group (71.0%) could be evaluated for the primary efficacy analysis. The primary efficacy outcome occurred in 27 patients in the apixaban group (1.4%) and in 74 patients in the enoxaparin group (3.9%) (relative risk with apixaban, 0.36; 95% confidence interval [CI], 0.22 to 0.54; P<0.001 for both noninferiority and superiority; absolute risk reduction, 2.5 percentage points; 95% CI, 1.5 to 3.5). The composite outcome of major and clinically relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban (4.8%) and 134 of 2659 assigned to enoxaparin (5.0%) (absolute difference in risk, −0.2 percentage points; 95% CI, −1.4 to 1.0). CONCLUSIONS Among patients undergoing hip replacement, thromboprophylaxis with apixaban, as compared with enoxaparin, was associated with lower rates of venous thromboembolism, without increased bleeding

Soluble Human Leukocyte Antigen-G Isoforms in Maternal Plasma in Early and Late Pregnancy

Problem Human Leukocyte Antigen (HLA)-G is a class Ib gene located in the human Major Histocompatibility Complex (MHC). Several lines of investigation indicate that the HLA-G molecule is involved in the maternal acceptance of the semi-allogenic fetus during pregnancy and in development of tolerance. Expression of soluble HLA-G (sHLA-G) is positively correlated with successful in vitro fertilization (IVF) treatments, and aberrant expression of HLA-G in certain complications of pregnancy, such as pre-eclampsia and spontaneous abortion, has been reported. Method of study Soluble HLA-G (sHLA-G) can be detected in maternal blood, and in this study, two different isoforms of sHLA-G, namely sHLA-G1 generated by shedding of membrane-bound HLA-G1 and HLA-G generated by specific HLA-G transcripts, have been investigated early (median of 16.4 weeks of gestation (GW)) and late (median: 38.9 GW) in pregnancy in an original cohort of 580 pregnant Caucasian women. Results Lower concentrations of sHLA-G1 were found late in pregnancy (>32 GW) in a group of women with severe pre-eclampsia compared with controls with uncomplicated pregnancies (P = 0.029, PC = 0.09; Mann-Whitney; Logistic regression analysis: P = 0.024, OR = 0.920, 95% CI 0.855-0.989). However, this was not the case with HLA-G5, and significant more of the cases with severe pre-eclampsia had detectable plasma HLA-G5 compared with the control group (P = 0.013, PC = 0.04; Mann-Whitney). Similar findings were not observed in women with gestational hypertension or existing hypertension continuing into pregnancy. Conclusion These results indicate that sHLA-G1 is the interesting soluble HLA-G isoform in pre-eclampsia. Furthermore, there was a trend towards lower maternal plasma sHLA-G1 in a group of women with premature birth (<37 GW) compared with the control group (P = 0.028, PC = 0.17; Mann-Whitney). To the contrary, HLA-G5 was lower in the control group compared to the premature group (P = 0.004, PC = 0.02; Mann-Whitney). Interestingly, a trend towards lower sHLA-G1/HLA-G5 and HLA-G1 plasma levels late in pregnancy were observed in women with their second or third partus compared to primipara (sHLA-G1/HLA-G5: P = 0.080, PC = 0.48; sHLA-G1: P = 0.017, PC = 0.10; Kruskal Wallis test)

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE.

BACKGROUND: Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. OBJECTIVES: Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). PATIENTS/METHODS: All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). RESULTS: In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. CONCLUSIONS: Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles

Estudo eritroleucométrico e proteinograma sérico do sangue do cordão umbilical e jugular de eqüinos ao nascimento e de suas respectivas mães Erythrocytometry and seric proteinogram of umbilical cord and jugular of foals at birth and respective mothers

Colheram-se amostras de sangue do cordão umbilical (SCU) e do sangue circulante de cinco eqüinos neonatos, imediatamente após o nascimento, e o sangue da própria mãe, utilizando-se um sistema a vácuo. O material foi submetido à contagem global de hemácias e leucócitos e à determinação do volume globular e da concentração de hemoglobina; à contagem diferencial de leucócitos em esfregaços sangüíneos; e ao cálculo dos índices eritrocitométricos. Foram realizadas a dosagem de proteínas séricas totais e a eletroforese das proteínas séricas em gel de agarose. Não houve diferenças significativas entre os parâmetros do SCU e do sangue da jugular dos potros. No SCU dos potros observaram-se valores mais elevados para contagem global de hemácias (9,75x10(6)/µl), dosagem de hemoglobina (14,65g/dl) e concentração de hemoglobina corpuscular média (37,23g/dl); e valores menores para volume corpuscular médio (40,50fl), proteína total (4,37g/dl), alfa-globulinas (0,65g/dl), beta-globulinas (1,10g/dl), gama-globulinas (0g/dl) e contagens global (5,40 x 10³/µl) e diferencial de leucócitos, exceto contagem de neutrófilos bastonetes e monócitos, quando comparados com os valores obtidos no sangue de suas mães.<br>Umbilical cord blood (UCB) and systemic blood samples were collected from five equine neonates, immediately after birth. Systemic blood samples from their mothers were also collected at the same time, using a vacuum system. The samples were submitted to the following analyses: red blood cell and total white blood cell counts; determinations of packed cell volume and hemoglobin concentration; differential white cell count in blood smears; and determination of erythrocytometric values. Total serum proteins quantification and serum proteins electrophoresis in agarose gel were done. No significant difference (P<0.05) was noted between averages in neonate jugular blood and equine UCB. Equine UCB showed higher values of red blood cell count (9.75x10(6)/µ), hemoglobin determination (14.65g/dl), and mean corpuscular hemoglobin concentration (37.23g/dl); but lower values of mean corpuscular volume (40.50fl), total protein (4.37g/dl), alpha-globulin (0.65 g/dl), beta-globulin (1.10g/dl), gamma-globulin (0g/dl), total (5.40x10³/µl), and differential leukocytes count, except for band neutrophils and monocytes counts, when compared to the blood of the mares