Thrombolysis for massive pulmonary embolism in pregnancy: a case report

Mortality from pulmonary embolism (PE) in pregnancy might be related to challenges in targeting the right population for prevention. Such targeting could help ensure that the correct diagnosis is suspected and adequately investigated, and allow the initiation of the timely and best possible treatment of this disease. In the literature to date only 18 case reports of thrombolysis in pregnant women with PE have been reported, and showed beneficial effects for both mother and fetus in terms of mortality and complications with acceptable bleeding risks. We present here the case of a pregnant patient with massive PE who underwent successful thrombolysis. A 26-year-old pregnant (at 24 weeks) woman was admitted 4 h after onset of sudden acute dyspnea and chest pain. An immediate electrocardiogram showed a typical S1-Q3-T3 pattern. The echocardiogram showed a distended right ventricle with free-wall hypokinesia and displacement of the interventricular septum toward the left ventricle. Thrombolysis with recombinant tissue plasminogen activator (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Pelvic examination and ultrasound showed regular fetal heart beat, and regular placental and liquid presence. No problems developed for the mother or fetus in the subsequent days or at discharge. In conclusion, in pregnant patients with life-threatening massive PE, thrombolytic therapy can be administered, and the use of echocardiographic, laboratory, and clinical data can be useful tools to achieve a rapid diagnosis and make a therapeutic decision, but additional studies need to be performed to further define its use

Treatment options in massive pulmonary embolism during pregnancy; A case-report and review of literature

Systemic thrombolysis with recombinant tissue plasminogen activator (rt-PA), streptokinase or urokinase is considered as high-risk treatment in pregnancy. However, several reports have described the successful use of systemic thrombolysis in pregnant patients with massive pulmonary embolism and haemodynamic instability. Case: We describe a 34-year old, pregnant female, who presented at 25 weeks of gestation with an acute collapse with reduced consciousness and shortness of breath caused by massive pulmonary embolism. Because of significant haemodynamic instability, increased right ventricular pressure and no improvement after intravenous heparin, thrombolytic therapy was administered. The response to thrombolytic therapy was excellent. No severe haemorrhagic complications were observed. Anticoagulant therapy with LMWH was continued until delivery. A healthy child was born at term. Review: In English literature, 13 patients received thrombolysis during pregnancy because of pulmonary embolism. No maternal deaths, four non-fatal maternal major bleeding complications, 30.8%;95%CI(9.1-61.4), two fetal deaths, 15.4%;95%CI(1.9-45.5), and five preterm deliveries, 38.5%;95%CI(13.9-68.4), were observed. Surgical embolectomy and catheter embolectomy or catheter thrombolysis has only been performed in 12 patients. Conclusion: The number of reports on thrombolytic therapy, surgical embolectomy and catheter embolectomy or thrombolysis for massive pulmonary embolism during pregnancy are limited. We suggest an international registry for pregnant patients undergoing thrombolysis or embolectomy to gain more information about these treatment options. Nevertheless, complication rates of thrombolytic therapy are acceptable in the light of the underlying disease, and in the meantime, current data do not justify withholding pregnant women from thrombolytic therapy in case of life-threatening PE. (C) 2009 Elsevier Ltd. All rights reserved

Use of the CD19 count in a primary care laboratory as a screening method for B-cell chronic lymphoproliferative disorders in asymptomatic patients with lymphocytosis

Background: Detection of absolute and relative lymphocytosis in otherwise asymptomatic elderly patients is very common in the primary care setting and frequently results in referral for screening of lymphoproliferative disorders. Since many B-cell chronic lymphoproliferative disorders (B-CLPD) are indeed asymptomatic at diagnosis in most patients with lymphocytosis, no sign of such a disorder is usually detected. Currently, specific guidelines for screening of patients with lymphocytosis are lacking. We investigated the practicability and clinical value of a single colour CD19 count performed by a primary care laboratory in order to improve the diagnostic follow-up of patients with lymphocytosis in a primary care laboratory. Methods: The capability of detecting monoclonal B-cell lymphocytosis and B-CLPD by CD19, was first confirmed in patient samples with known B-CLPD. Next, in a previously defined geographic area, a CD19 count was performed on all samples for patients aged >= 40 years with relative or absolute lymphocytosis but without neutropenia. Clinical follow-up, with a median of 4 years, was performed using both a survey among the requesting general practitioners and by analysis of the records of the referral hospitals within the borders of the defined area. Results: A total of 520 cases with asymptomatic lymphocytosis were identified. In all cases, the CD19 count was performed; 207 (40%) showed increased values and 313 (60%) showed normal values. An increase in CD19 proved highly sensitive for detection of B-CLPD (98%, 95% CI; 94%-100%) with a high positive predictive value (57%, 95% CI; 50%-63%). The area under curve, the receiver-operating characteristic curve of the CD19 count (0.93, 95% CI; 0.91-0.96), was significantly higher compared to the absolute lymphocyte count (0.86, 95% CI; 0.83-0.89), especially in patients with moderate lymphocytosis. Conclusions: This study indicates that the CD19 count, performed by a primary care laboratory, is feasible and a promising tool for initial screening of lymphocytosis to discriminate B-CLPD from benign causes of lymphocytosis

Dasatinib in combination with fludarabine in patients with refractory chronic lymphocytic leukemia: a multicenter phase 2 study

Item does not contain fulltextResistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti-apoptotic regulators and restores fludarabine sensitivity in activated CLL. The aim of this study was to evaluate efficacy of one cycle of dasatinib monotherapy (100mg/day, days 1-28) followed by combination of dasatinib with fludarabine (40mg/m(2)/day, days 1-3 every 28 day) for a total of 6 cycles in fludarabine-refractory CLL. The primary endpoint was overall response rate according to the IWCLL'08 criteria. 20 patients were enrolled: 18 completed at least one cycle of treatment of which 67% finished at least 2 cycles of combination treatment. 3 of these 18 patients reached a formal PR (16.7%). Majority of patients obtained some reduction in lymph node (LN) size. Most frequent toxicity was related to myelosuppression. NF-kappaB RNA expression levels of circulating CLL cells decreased whereas the levels of pro-apoptotic NOXA increased during treatment. In conclusion, dasatinib/fludarabine combination has modest clinical efficacy in fludarabine-refractory patients

Overview of available p53 function tests in relation to TP53 and ATM gene alterations and chemoresistance in chronic lymphocytic leukemia

The ATM-p53 DNA damage response pathway plays a crucial role in chemoresistance in chronic lymphocytic leukemia, as indicated by the adverse prognostic impact of deletions of 17p (locus of TP53) and 11q (locus of ATM) detected by fluorescence in situ hybridization (FISH) analysis. In addition to deletions, mutations in these respective genes are also associated with chemoresistance, and add to the prognostic information provided by FISH. In order to explore the possibility that dysfunction of the ATM-p53 pathway might also result from mechanisms other than ATM/TP53 deletion/mutation, assays have been developed that probe the functional integrity of the ATM-p53 pathway. Currently, four different p53 function assays have been developed that are based on the measurement of p53 and p53-dependent genes at the RNA (real-time polymerase chain reaction [RT-PCR]p21; RT-PCRmiR34a; reverse transcription-multiplex ligation-dependent probe amplification assay [RT-MLPA]p21, bax, puma and CD95) or protein (fluorescence activated cell sorting [FACS]p53-p21) level in untreated cells or following irradiation or drug treatment. Here we provide an overview of these assays based on the available literatur

Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16·3%, 16·9%, 10·7%). We found evidence for subclonal mutations in 67·5% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CL