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Biomedical subjects

Benjamin Brenner

Publications and source records attributed to Benjamin Brenner.

At least 19 recordsLinked to original sources
PubMed2006

A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages.

OBJECTIVE: To compare the effect of aspirin and enoxaparin on live births in women with unexplained recurrent miscarriages, as well as secondary outcomes including birth weight, uterine and umbilical blood flows, and congenital malformations. DESIGN: Multicenter randomized comparative cohort study. SETTING: Four centers including two university hospitals, a peripheral general hospital, and a community health clinic. PATIENT(S): One hundred seven patients were randomized, 104 were available for analysis; 54 were randomized to enoxaparin and 50 to aspirin. INTERVENTION(S): Treatment with enoxaparin or aspirin in subsequent pregnancy. MAIN OUTCOME MEASURE(S): Subsequent live births or miscarriage, and the incidence of obstetric complications. RESULT(S): Both groups had a similar live birth rate (relative risk = 0.92, 95% confidence interval: 0.58-1.46). In primary aborters, live births occurred in 17 of 18 (94%) enoxaparin-treated pregnancies compared to 18 of 22 (81%) aspirin-treated pregnancies. In the aspirin group, two pregnancies were terminated: for tricuspid insufficiency and for hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. One enoxaparin-treated infant was growth restricted (2,020 g) at 36 weeks. Preeclampsia was found in three aspirin-treated patients. Preterm delivery, placental Doppler blood flow, apgar scores, and mean birth weights were similar in both groups. In the aspirin group, one infant underwent orchidectomy after testicular torsion in utero, and one infant had hypoglycemia and convulsions. CONCLUSION(S): Both regimens were associated with a high live birth rate and few late pregnancy complications.

Abortion, Habitual↗
PubMed2006

Thrombophilia and adverse pregnancy outcome.

This article focuses on the clinical evaluation and management of women who have thrombophilia-related placental vascular complications, including fetal loss, pre-eclampsia, intrauterine fetal growth restriction, and placental abruption. All are major causes of maternal and fetal adverse outcomes.

Abortion, Spontaneous↗
PubMed2006

A fatal case of enoxaparin induced skin necrosis and thrombophilia.

Skin necrosis caused by heparins is a rare complication. We report a case of a 71-yr-old white woman who developed painful diffuse skin lesions, most probably related to enoxaparin treatment. Other causes of skin necrosis, including heparin induced thrombocytopenia, disseminated intravascular coagulation, protein C/protein S deficiencies, anti-phospholipid antibodies, and vitamin K deficiency were less likely in this case. The concomitant combined thrombophilia possibly aggravated the patient's clinical presentation.

Aged↗
PubMed2006

Thrombophilia and pregnancy complications.

Thrombophilic risk factors are common and can be found in 15% to 25% of Caucasian populations. Since pregnancy is an acquired hypercoagulable state, women harboring thrombophilia may present with clinical symptoms of vascular complications for the first time during gestation or at the postpartum period(1). Women with thrombophilia may have an increased risk of placental vascular complications, including pregnancy loss, preeclampsia, intrauterine growth restriction,and placental abruption. Accumulating data suggest that maternal antithrombotic prophylaxis may result in improved gestational outcome. Randomized trials are under way and hopefully will optimize maternal and neonatal outcome.

Adult↗
PubMed2006

Prevalence of upper extremity deep venous thrombosis diagnosed by color Doppler duplex sonography in cancer patients with central venous catheters.

OBJECTIVE: The purpose of this study was to review the literature concerning upper extremity deep venous thrombosis (UEDVT) diagnosed by color Doppler duplex sonography (CDDS) in cancer patients with indwelling central venous catheters (CVCs). METHODS: From computerized databases (MEDLINE and Ovid), relevant publications regarding CDDS of the upper limb veins in cancer patients with CVCs were reviewed. RESULTS: Patients with malignancy have a higher rate of thrombosis, which is increased by the presence of CVCs. Screening CDDS in asymptomatic patients showed CVC-related UEDVT in 11.7% to 44% of patients. In symptomatic cancer patients, the range was similar to the asymptomatic ones, 6.7% to 48%. The presence of a CVC almost doubled the incidence of UEDVT in symptomatic patients. Color Doppler duplex sonography is an accurate examination for the diagnosis of UEDVT, with sensitivity ranging from 78% to 100% and specificity ranging from 82% to 100%. The main obstacle for the diagnosis of UEDVT is the presence of overlying bones, making it difficult to visualize and impossible to directly assess by compression techniques. Color and spectral Doppler sonography and the use of small transducers aid in the diagnosis. When several parameters are evaluated in combination, CDDS is a reliable method for diagnosing CVC-related thrombosis. CONCLUSIONS: Great variability in the prevalence of catheter-related thrombosis in cancer patients has been reported, although it is uniformly higher compared with patients without cancer. Color Doppler duplex sonography is the modality of choice for the diagnosis of CVC-related UEDVT in symptomatic cancer patients and for screening for asymptomatic thrombosis in this specific population.

Catheterization, Central Venous↗
PubMed2006

Evaluation of ProC Global assay in women with a history of venous thromboembolism on hormonal therapy.

The risk of thrombosis in women increases significantly during treatment with hormonal therapy (HT). The aim of this study was to evaluate ProC Global assay in women with a history of venous thromboembolism (VTE) while using HT. Protein C activation time normalized ratio (PCAT-NR) levels were significantly lower in 32 women with a history of VTE while using HT (0.72 +/- 0.1) compared with 56 healthy controls without HT, matched by age at blood sampling (0.99 +/- 0.2) and 40 healthy controls with HT, matched by age and HT at VTE event (0.94 +/- 0.2) (P < 0.001 for both). PCAT-NR lower than the cut-off level of 0.8 was found in 23/32 (72%) patients compared with 5/56 (9%) age-matched controls (OR = 26, 95%CI: 7-106, P < 0.001) and 9/40 (22.5%) of HT-matched controls (OR = 9, 95%CI: 2.7-30, P < 0.001). Any thrombophilic risk factor was found in 20/32 (62.5%) of patients compared with 12/56 (21.4%) of agematched controls (OR = 6, 95%CI: 2.1-10, P < 0.001) and 12/40 (30%) of HT-matched controls (OR = 4, 95%CI: 1.3-11.8, P = 0.006). Out of the variables that are risk factors of VTE as age, HT or thrombophilic risk factor, ProC Global assay was found in the multivariate analysis - logistic regression, as the parameter that was the most associated with patient group [Exp(B) = 15.8, 95% CI: 4.2-59.0, P < 0.001]. In conclusion, abnormal PCAT-NR is associated with VTE in women using HT. ProC Global assay may potentially serve as a diagnostic tool for evaluating the risk of VTE in women prior to administration of HT.

Adult↗
PubMed2006

Prospective evaluation of patients hospitalized with venous thromboembolism: comparison between cancer and non-cancer patients.

BACKGROUND: Little is known about the epidemiology of venous thromboembolism in hospitalized patients in Israel. Also, a direct comparison of the clinical and laboratory features between cancer and non-cancer patients has not yet been reported. OBJECTIVES: To investigate and compare the epidemiologic, clinical and laboratory characteristics of cancer and non-cancer patients hospitalized with venous thromboembolism in a large referral medical center in Israel. METHODS: Between February 2002 and February 2003, patients diagnosed at the Rambam Medical Center as suffering from VTE (deep vein thrombosis and/or pulmonary embolism), based on diagnostic findings on Doppler ultrasonography, spiral computed tomography scan or lung scan showing high probability for pulmonary embolism, were prospectively identified and evaluated. In addition, at the conclusion of the study period, the reports of spiral chest CT scans, performed during the aforementioned period in this hospital, were retrospectively reviewed to minimize the number of unidentified cases. Blood samples were drawn for evaluation of the coagulation profile. RESULTS: Altogether, 147 patients were identified and 153 VTE events diagnosed, accounting for 0.25% of all hospitalizations during the study period. The cancer group included 63 patients (43%), most of whom had advanced disease (63%). The most common malignancies were cancer of the lung (16%), breast (14%), colon (11%) and pancreas (10%). Of 122 DVT events (with or without pulmonary embolism) there were 14 upper extremity thromboses (12%). The most common risk factors for VTE, except malignancy, were immobilization (33%), surgery/trauma (20%) and congestive heart failure (17%). There was no difference in prevalence of various risk factors between cancer and non-cancer patients. During an acute VTE event, D-dimer levels were higher in cancer patients than non-cancer patients (4.27 +/- 4.04 vs. 2.58 +/- 1.83 mg/L respectively, P = 0.055). Relatively low values of activated protein C sensitivity ratio and normalized protein C activation time were observed in both cancer and non-cancer groups (2.05 +/- 0.23 vs. 2.01 +/- 0.33 and 0.75 +/- 0.17 vs. 0.71 +/- 0.22, respectively). These values did not differ significantly between the groups. CONCLUSION: The proportion of cancer patients among patients suffering from VTE was high. Their demographic, clinical and laboratory characteristics (during an acute event) were not different from those of non-cancer patients, except for higher D-dimer levels.

Adolescent↗
PubMed2005

Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia-a single center experience in 34 patients.

In this retrospective study, the hemorrhagic and thrombotic events are reported at presentation and during induction in 34 consecutive acute promyelocytic leukemia (APL) patients treated in a single referral center. The most consistent hemostatic abnormality was decreased fibrinogen level (<150 mg/dL) found in 21 patients (61%), partial thromboplastin time (PTT) was normal almost in all patients. A mildly prolonged prothrombin time (PT) was observed in 14 patients (44%). Median platelet count was 30.10(9)/L (range 3-191.10(9)/L). Life-threatening bleeding manifestations occurred in 10 patients (29%). By multivariate analysis, severe bleeding complications did not correlate with hemostatic parameters but did correlate with white cell count at presentation. Four patients (12%) had severe thrombotic events, two cerebral sagital sinus thrombosis, one pulmonary embolism, and one subclavian vein thrombosis. Two other patients had pseudotumor cerebri. Three out of six patients with thrombotic events were found to have thrombophilia. These results may suggest an association between thrombophilia and thrombosis in APL patients. Two patients suffered from combined severe bleeding and thrombosis. Hemostatic parameters are not helpful in predicting neither hemorrhage nor thrombosis.

Adolescent↗
PubMed2005

Meeting report. Acute promyelocytic leukemia-associated coagulopathy, 21 January 2004, London, United Kingdom.

Despite successful treatment with all-trans retinoic acid and chemotherapy, life-threatening bleeding remains a challenging complication of acute promyelocytic leukemia (APL). Indeed, bleeding and thrombosis are major complications of APL that lead to early death in approximately 10% of patients despite the success of current treatment. This condition may be attributed, in part, to the diffuse activation of coagulation, hyperfibrinolysis, and non-specific proteolytic activity that is observed in patients with APL. Therapeutic agents that induce the differentiation of leukemia cells improve outcomes compared with those observed using chemotherapy alone. They also correct the hyperactivity of the coagulation and fibrinolytic systems, thereby reducing early death from bleeding. Prophylactic therapy with newer anticoagulants may prove beneficial in patients with APL, but this must be confirmed in well-designed, randomized, controlled trials. A workshop was convened 21 January 2004 in London, England, to discuss the clinical and biological aspects of the APL-associated coagulopathy and the application of recent findings to the management of patients with APL. Eight speakers participated in the workshop. This meeting report provides synopses of their presentations and a summary of highlights from the meeting.

Anticoagulants↗
PubMed2005

Thrombophilia related issues in women and children.

Women experience increased thrombotic risk at pregnancy and puerperium as well as during hormonal therapy with oral contraceptives or hormone replacement therapy. Physiological and anatomical changes in pregnancy contribute to the hypercoagulable situation. Women with thrombophilia have an increased risk for venous and arterial thromboembolism as well as for gestational vascular complications including fetal loss, pre-eclampsia, placental abruption, and fetal growth restriction. Children are at increased thrombotic risk, particularly at the neonatal period, and may express thrombosis often in association with thrombophilia. This article will focuses on the clinical association, pathogenesis, and treatment of thrombophilia-related issues in women and children.

Anticoagulants↗
PubMed2005

Modulation of systemic hemostatic parameters by enoxaparin during gestation in women with thrombophilia and pregnancy loss.

Recurrent pregnancy loss (PL) is associated with maternal thrombophilia and prophylaxis with low molecular weight heparin (LMWH) can improve pregnancy outcome in this setting. The aim of this study was to investigate the modulation of systemic hemostatic parameters by enoxaparin in women with recurrent PL and to evaluate plasmatic parameters that would potentially enable monitoring LMWH prophylaxis effect during pregnancy. Study group included 87 women with thrombophilia and PL treated with enoxaparin 40 mg daily vs. 40 mg twice daily. The control group comprised 40 women with normal pregnancies. Blood samples have been collected throughout the period starting at 5-10 weeks of gestation until 6-10 weeks postpartum. The determined plasmatic markers included: anti-Xa activity, total and free tissue factor pathway inhibitor (TFPI), D-dimer, prothrombin fragment 1+2 (PT1+2), activated protein C resistance (APC-SR) and free protein S. Successful pregnancy outcome was recorded in 70 (80.5%) women treated with enoxaparin, without correlation to enoxaparin dosage. Seventeen women (19.5%) had pregnancy loss at 16+/-7 (6-32) weeks of gestation. Anti-Xa levels at 10-15 weeks of gestation were higher (0.39+/-0.38 u/ml) in the successful pregnancy outcome group compared to the abortion group (0.22+/-0.2 u/ml). Prophylactic anti-Xa activity levels (0.28+/-0.13 u/ml) were documented from 15 weeks of gestation until delivery in the successful pregnancy outcome group. Significant increase in anti-Xa, total TFPI and free TFPI levels (P<0.001) was achieved after beginning of LMWH prophylaxis in successful pregnancy outcome group but not in the abortion group. D-dimer and PT1+2 levels appeared to be significantly increased while APC-SR and free protein S levels gradually decreased during pregnancy, with no difference between study groups. These results suggest that LMWH prophylaxis during pregnancy enables modulation of systemic hemostatic parameters via inhibition of factor Xa and increase in plasmatic total and free TFPI levels.

Abortion, Habitual↗
PubMed2005

Control of bleeding caused by thrombocytopenia associated with hematologic malignancy: an audit of the clinical use of recombinant activated factor VII.

This paper presents an analysis of 24 cases in which recombinant factor VIIa (rFVIIa) was used in the management of hemorrhage in patients with thrombocytopenia associated with hematologic malignancies. This is the largest case aggregation to date and focuses on preliminary experience in the off-label use of this hemostatic agent. Data were extracted from the international, Internet-based registry, www.haemostasis.com, accessed in September 2003. The search results were manually cross-checked against monthly summary reports. The physicians providing the cases were contacted individually to approve the use of their cases, supply any information missing from the database, and validate the data already held. Patients with acute myeloid leukemia, acute lymphoblastic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, Burkitt's lymphoma, B-cell or T-cell lymphoma, or aplastic anemia received rFVIIa at total doses of between 18 and 1040 mug/kg body weight. Bleeding stopped in 11 of 24 (46%) patients, markedly decreased in 8 of 24 (33%) patients, and decreased in 4 of 24 (17%) patients. In most patients, the response was achieved within 2.5 hours of administration of rFVIIa. The use of rFVIIa was generally well tolerated -- 1 case of ischemic stroke was considered to be possibly related to rFVIIa administration, but this has yet to be confirmed. A review of these 24 cases submitted to the www.haemostasis.com database suggests that rFVIIa is beneficial in the management of hemorrhage in patients with thrombocytopenia and hematologic malignancies. This warrants further investigation in rigorously controlled clinical trials.

Adolescent↗
PubMed2005

[Spontaneous umbilical cord hematoma].

BACKGROUND: Spontaneous umbilical cord hematoma is rare and might be associated with fetal death. CASE: An emergency cesarean section was performed on a woman during the 41st week of gestation due to fetal distress. A stretched umbilical cord with hematoma was evident. The infant had tachypnea without any other physical or neurological damage. We speculate that traction of the cord led to a tear of an umbilical vessel, cord hematoma, compression of cord vessels and fetal compromise. CONCLUSION: In case of early prenatal diagnosis of spontaneous umbilical hematoma accompanied with signs of fetal distress, labor should be considered.

Adult↗
PubMed2005

Hemostatic balance on the surface of leukemic cells: the role of tissue factor and urokinase plasminogen activator receptor.

BACKGROUND AND OBJECTIVES: The frequency of thrombotic complications is increased in patients with acute leukemia. Since coagulation processes take place on cell membranes, we hypothesized that expression of coagulation proteins on blast membrane could determine the hemostatic balance on the surface of leukemic cells and may correlate with thrombotic manifestations. DESIGN AND METHODS: Fifty-one consecutive patients with newly diagnosed acute leukemia were enrolled over an 11-month period. Twenty-five of the patients had acute myeloid leukemia (AML)-M(0-2), 11 had AML-M3, 6 had AML-M(4-5), and 9 acute lymphocytic leukemia (ALL). Peripheral blood and bone marrow were analyzed by flow-cytometry for tissue factor, protease-activated receptor 1, tissue factor pathway inhibitor, urokinase plasminogen activator receptor, and thrombomodulin. RESULTS: Regardless of the leukemia subtype, tissue factor was predominantly present on leukemic blast surfaces as compared to protease-activated receptor 1, tissue factor pathway inhibitor, urokinase plasminogen activator receptor and thrombomodulin and it was significantly elevated (mean 63+/-6%) in AML-M3 and AML-M(4-5) as compared to AML-M0(-2) and ALL (mean 37+/-4%, p<0.001). Likewise, urokinase plasminogen activator receptor expression was greater in AML-M(4-5) (49+/-11%) than in in AML- M(0-2), M3 and, ALL (mean 17+/-3%, p<0.001). Thrombotic manifestations were present in 13 out of 51 (26%) patients. The tissue factor to urokinase plasminogen activator receptor ratio was higher in patients with a thrombotic event than in patients without thrombotic events (16+/-4 vs. 6+/-2, p=0.042). INTERPRETATION AND CONCLUSIONS: This study demonstrates that tissue factor predominates on leukemic blast surface, particularly in M3 and M4-5 subtypes, while urokinase plasminogen activator receptor is increased on M4-5 blasts. The hemostatic balance on the blast surface may contribute to thrombotic manifestations in leukemic patients.

Adult↗
PubMed2004

Drug-related thrombosis in hematologic malignancies.

Cancer patients are at increased risk for thrombosis. Among the predisposing factors for the hemostatic imbalance, drugs have a definite role. Induction of thrombosis by drugs involves a variety of mechanisms: Enhancement of procoagulant activity, reduction in anticoagulants synthesis, stimulation of platelet aggregation and endothelial damage. L-asparaginase is associated with thrombotic events, mainly in the venous system. Supportive therapy with fresh frozen plasma is probably insufficient and heparin needs further evaluation. Venous thromboembolism has recently emerged following thalidomide use particularly in combination chemotherapy. The hematopoietic growth factors granulocyte colony-stimulating factor, macrophage-granulocyte colony-stimulating factor and erythropoietin have also been implicated in venous as well as in arterial thrombotic events. Numerous drugs are associated with thrombotic microangiopathy i.e., cyclosporine A, tacrolimus, cisplatin, bleomycin, gemcitabine. The clinical presentation, pathological mechanisms and therapeutic modalities are discussed.

Antineoplastic Agents↗
PubMed2004

Clinical management of thrombophilia-related placental vascular complications.

Pregnancy is a hypercoagulable state with an increased thrombotic risk throughout gestation and the postpartum period. Women with thrombophilia may have a further increased risk of placental vascular complications, including pregnancy loss, preeclampsia, intrauterine growth restriction, and placental abruption. Preliminary data suggest that maternal antithrombotic prophylaxis may result in improved gestational outcome. Randomized trials are under way and hopefully will optimize maternal and neonatal outcome.

Adult↗