49 research outputs found
Acute generalized, widespread bleeding. Diagnosis and management
BACKGROUND AND OBJECTIVE: Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding.
INFORMATION SOURCES: The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis.
STATE OF ART AND PERSPECTIVES: DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are require
Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? A meta-analysis
We compared the efficacy and safety of low molecular
weight heparins (LMWH) and unfractionated heparin (UFH) in the treatement of deep
venous thrombosis (DVT). A comparison between two daily subcutaneous injections
of LMWH against a single injection was also performed. DESIGN AND METHODS: The
study was performed by a meta-analysis. Clot improvement in venography,
recurrency, total mortality and major hemorrhages were assessed in 4,472 patients
with DVT from 21 studies treated with subcutaneous LMWH or UFH. RESULTS: An
improvement in clot reduction (odds ratio 0.73, 95% confidence interval 0.59 to
0.90, p = 0.004), a decrease in total mortality (0. 68, 0.50 to 0.91, p = 0.012)
and a lower incidence of hemorrhage (0. 65, 0.43 to 0.98, p = 0.047) were
observed in LMWH treated patients. There were no differences in recurrences
(0.78, 0.59 to 1.04, p = 0. 10). A single dose of LMWH was better than two in
reducing major bleeding (c2 = 4.99, p = 0.025); however, the two dose regimen was
more effective in clot reduction (c2 = 8.56, p = 0.004). INTERPRETATION AND
CONCLUSIONS: LMWH is superior to UFH in terms of safety and efficacy. A single
daily dose of LMWH dose is a suitable therapeutic regimen and could facilitate
the outpatient treatment of venous thromboembolism
Emergence of Secondary Acute Leukemia in a Patient Treated for Osteosarcoma: Implications of Germline TP53 Mutations
Secondary leukemia and myelodysplastic syndromes have been reported
in patients following treatment for a wide range of neoplastic disorders. However
second malignancies after chemotherapy and/or irradiation for osteosarcoma are
unusual. PROCEDURE: We report the case of a 15-year-old girl who developed a
myelodysplastic syndrome with evolution to acute nonlymphocytic leukemia after
treatment for osteosarcoma. Therapy-related acute leukemia karyotype findings
such as abnormalities of chromosomes 5, 7, and 17 were found in the cytogenetic
analysis. Moreover, using denaturing gradient gel electrophoresis and DNA
sequencing, we detected the presence of a double germline mutation in exon 7 of
the TP53 gene. CONCLUSION: This observation supports the possibility of a causal
relationship between germline TP53 mutations and the development of secondary
leukemia and myelodysplasi
Long-term cardiac rehabilitation program favorably influences fibrinolysis and lipid concentrations in acute myocardial infarction
BACKGROUND AND OBJECTIVE: The control of well-known atherosclerotic risk factors represents the optimal strategy in the prevention of acute coronary syndromes. It was the aim of this work to analyze the effects of a long-term cardiac rehabilitation program on the changes of fibrinolysis parameters and plasma lipid profile in coronary patients.
DESIGN AND METHODS: The study was carried out in 30 (M/F:22/8, mean age 47 years) survivors of a first acute myocardial infarction (AMI) and in 30 healthy controls who underwent a cardiac rehabilitation program (9 months duration). Samples were taken before, at 3 and 9 months after the beginning of the program to measure: tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI-1) activity and antigen. A lipid profile including cholesterol (both HDL and LDL) and lipoprotein(a) was also assessed. The Wilcoxon and Mann-Whitney tests were used for statistical comparisons.
RESULTS: There was a marked decrease of functional PAI-1 after 3 and 9 months as compared with baseline in AMI patients (p < 0.01). Results showed a significant increase of HDL-cholesterol (p < 0.01) and decrease of lipoprotein(a) levels after the exercise program (p < 0.01).
INTERPRETATION AND CONCLUSIONS: The cardiac rehabilitation program improved fibrinolysis, by reducing the functional levels of PAI-1, and ameliorated the lipid profile by decreasing lipoprotein(a) and increasing HDL-cholesterol in patients with AMI. A long-term cardiac rehabilitation has positive effects on some risk factors for coronary disease
Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study
Rituximab is a standard treatment for non-Hodgkin diffuse large B-cell
(DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was
developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration-related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety
of switching from intravenous to subcutaneous administration of rituximab
during first-line induction/maintenance for DLBCL or FL, focusing on
ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients
received subcutaneous rituximab plus standard induction chemotherapy for
DLBCL or FL for 4â7 cycles, and/or every 2 months maintenance
monotherapy for FL for 6â12 cycles. The study included 140 patients:
DLBCL, n = 29; FL, n = 111. Ninety-five percent of patients experienced
adverse events, reaching grade â„3 in 38 6% and were serious in 30 0%.
AARs occurred in 48 6%, mostly (84 9%) at the injection site, with only
2 1% of patients reaching grade 3. The end-of-induction complete/unconfirmed complete response rate was 69 6%. After a median follow-up of
33 5 months, median disease-/event-/progression-free and overall survivals
were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL-5D a
good quality-of-life perception at induction/maintenance end. Therefore,
switching to subcutaneous rituximab showed no new safety issues and
maintained efficacy with improved satisfaction and quality of life
Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6
Ibrutinib may inhibitintestinal CYP3A4 and induce CYP2B6 and/or CYP3A. Secondary
to potential induction, ibrutinib may reduce the exposure and effectiveness of oral
contraceptives (OCs). This phase I study evaluated the effect of ibrutinib on the pharmacokinetics of the CYP2B6 substrate bupropion, CYP3A substrate midazolam, and
OCs ethinylestradiol (EE) and levonorgestrel (LN). Female patients (N = 22) with B-cell
malignancies received single doses of EE/LN (30/150 ÎŒg) and bupropion/midazolam
(75/2 mg) during a pretreatment phase on days 1 and 3, respectively (before starting ibrutinib on day 8), and again after ibrutinib 560 mg/day for â„ 2 weeks. Intestinal
CYP3A inhibition was assessed on day 8 (single-dose ibrutinib plus single-dose midazolam). Systemic induction was assessed at steady-state on days 22 (EE/LN plus ibrutinib) and 24 (bupropion/midazolam plus ibrutinib). The geometric mean ratios (GMRs;
test/reference) for maximum plasma concentration (Cmax) and area under the plasma
concentration-time curve (AUC) were derived using linear mixed-effects models (90%
confidence interval within 80%-125% indicated no interaction). On day 8, the GMR
for midazolam exposure with ibrutinib coadministration was †20% lower than the reference, indicating lack of intestinal CYP3A4 inhibition. At ibrutinib steady-state, the
Cmax and AUC of EE were 33% higher than the reference, which was not considered
clinically relevant. No substantial changes were noted for LN, midazolam, or bupropion. No unexpected safety findings were observed. A single dose of ibrutinib did not
inhibit intestinal CYP3A4, and repeated administration did not induce CYP3A4/2B6,
as assessed using EE, LN, midazolam, and bupropion