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Biomedical subjects

F Boehlen

Publications and source records attributed to F Boehlen.

At least 19 recordsLinked to original sources
PubMed2006

[Anticoagulation in patients with chronic renal failure].

Anticoagulation may be difficult to implement in patients suffering from chronic renal failure on account of platelet disorders and impaired clearance of some anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is necessary, more frequent testing of coagulation pathways may be required when these drugs are used in patients with renal failure. Long-term use of LMWH should be implemented cautiously with regular testing of anti-factor Xa activity and a half-dose may be advocated in patients with a creatinine clearance < 30 ml/mn. Danaparoid and thrombin inhibitors should be used mainly in patients suffering from renal failure and heparin-induced thrombocytopenia with regular monitoring of coagulation tests.

Anticoagulants↗
PubMed2006

Thrombocytopenia during pregnancy. Importance, diagnosis and management.

Thrombocytopenia is observed in 6 to 15% of pregnant women at the end of pregnancy, and is usually moderate. Gestational thrombocytopenia (defined as a mild thrombocytopenia, occurring during the 3 rd trimester with spontaneous resolution postpartum and no neonatal thrombocytopenia) is the most common cause of thrombocytopenia during pregnancy but a low platelet can also be associated with several diseases, either pregnancy specific or not, such as preeclampsia, HELLP syndrome, or idiopathic thrombocytopenic purpura (ITP). The differential diagnosis between ITP and gestational thrombocytopenia is clinically important with regard to the fetus, due to the risk of neonatal thrombocytopenia. However, this differential diagnosis is very difficult during pregnancy. Thrombocytopenia which need to be investigated are the following: thrombocytopenia known before pregnancy, thrombocytopenia occurring during the 1(st) and 2(nd) trimester, platelet count <75 G/l in the 3(rd) trimester or thrombocytopenia in case of pregnancy with complications. Investigations have to be discussed in function of history and clinical examination, gestational age and severity of thrombocytopenia. No treatment is required in case of gestational thrombocytopenia. There are few data to distinguish management of ITP between pregnant and non-pregnant women but management is different because of the potential adverse effects of the treatment for the woman and/or the fetus, the requirement for a good hemostasis at delivery and the risk of neonatal hemorrhage. One important problem is that it is not possible to predict the risk of neonatal thrombocytopenia in babies born from women with ITP.

Female↗
PubMed2005

[Menorrhagia and hemostatic abnormalities: diagnosis and treatment].

Menorrhagias consisting of heavy menstrual bleeding are a common complaint, encountered in approximately 15% of women between the ages of 30 and 50. Diagnosis is difficult because women present different forms of excessive menses and no simple objective ways of measuring menstrual blood loss exist. A pictorial blood assessment chart was therefore validated for a better management of heavy menstrual bleeding. In half of the cases, no gynaecologic cause is found. Therefore, blood tests should be performed aiming at identifying coagulation disorders. We present here the results of our small series. Identification of coagulation disorders may allow specific treatments. These improve the quality of life and prevent unnecessary radical measures such as notably, hysterectomies.

Blood Coagulation Disorders↗
PubMed2005

[Changes in D-dimer levels during pregnancy and the postpartum period: results of two studies].

In outpatients D-dimer (DD) measurement is included in most algorithms to exclude venous thromboembolism (VTE). We have recently performed two studies to evaluate the evolution of DD during pregnancy and the postpartum. During pregnancy, DD increase progressively and are of poor value to exclude VTE after 20 weeks of gestation. During labour, DD are usually very high and decrease quickly during the first 3 days post-delivery. Many weeks are necessary to obtain their normalisation and therefore their utility to rule out VTE is very limited until 4 weeks postpartum. This increase of DD values until 4 to 6 weeks after delivery correlates with the length of antithrombotic prophylaxis recommended for women at high risk of VTE.

Adult↗
PubMed2005

[Haemostasis. A search for an ideal antithrombotics agent].

Heparins and vitamin K antagonist are the main antithrombotic agents used since several years. These two classes of drugs are very effective but not devoid of side effects and require either injections or regular laboratory controls. Therefore new agents have been developed. Two of these agents (fondaparinux and ximelagatran) are already available. Both are of non animal origin, do not induce thrombocytopenia and do not require laboratory controls. In recent studies fondaparinux has shown a better efficacy than low molecular weight heparin in major orthopedic interventions. Ximelagatran, which can be given orally, is now admitted also for short term use. It was hoped that it could replace vitamin K antagonists but increase of liver enzymes occurring after a few weeks is a major problem. Other new drugs are in advanced stage and will be also described.

Factor Xa Inhibitors↗
PubMed2005

Not all statins interfere with clopidogrel during antiplatelet therapy.

BACKGROUND: Clopidogrel and statins are frequently coadministered in patients with ischemic heart diseases. Recent reports suggested that clopidogrel's effectiveness in inhibiting adenosine diphosphate (ADP)-induced platelets aggregation is attenuated by co-administration of certain statins. The objective of the present study was to define which statin might interfere with the antiaggregation property of clopidogrel. METHODS: We designed a pharmacokinetic study and tested ex vivo platelet function on 21 healthy volunteers who received clopidogrel and all currently commercially available statins: rosuvastatin [10 mg o.d.], simvastatin [20 mg o.d.], fluvastatin [80 mg o.d.], pravastatin [40 mg o.d.], and atorvastatin [20 mg o.d.]. Each statin was administered for 7 days followed by 1 week of wash-out period with clopidogrel treatment alone. Detection of the statins in the plasma was performed on all blood samples, using HPLC analytical method. RESULTS: All individuals, except one, were responders to clopidogrel with inhibition of ex vivo ADP induced platelet aggregation. All statins, except pravastatin, were detectable in the plasma at the end of each treatment period in all patients, and no statin was detectable after any of the wash-out periods. Clopidogrel was significantly less efficient to prevent platelet aggregation when coadministrated with simvastatin or fluvastatin. No difference was observed in clopidogrel efficacy when coadministered with rosuvastatin, pravastatin or atorvastatin. CONCLUSIONS: This is the first study investigating clopidogrel-statin interactions on ex vivo platelet function with all commercially available statins and which were administered to the same individuals. It demonstrates in healthy volunteers that at the doses used in this study, simvastatin and fluvastatin, but not atorvastatin, pravastatin or rosuvastatin interfere with the anti-aggregation effect of clopidogrel.

Adult↗
PubMed2005

D-dimer levels during delivery and the postpartum.

BACKGROUND: D-dimer (DD) measurement has proved to be very useful to exclude venous thromboembolism (VTE) in outpatients. However, during pregnancy, the progressive increase as well as the interindividual variations of DD means that in this instance they are of poor value to rule out VTE. Only a few studies have reported measurements of DD levels in the postpartum. OBJECTIVES: To measure DD sequentially in the puerperium in order to determine when DD levels return to values obtained in non-pregnant women and can again be used in the exclusion of VTE. PATIENTS AND METHODS: After uncomplicated pregnancies, 150 women delivering at term either vaginally (n = 100) or by cesarean section (n = 50) were included. DD levels were measured immediately following delivery and next at days 1, 3, 10, 30 and 45. RESULTS: There was a marked elevation of DD at delivery, especially when instrumental. All DD measurements were above 500 ng mL(-1) at delivery, at day 1 and at day 3 postpartum. A sharp decrease in DD was observed between day 1 and day 3, followed by a slight increase at day 10. At day 30 and day 45, respectively, 79% and 93% of women in the vaginal delivery group and 70% and 83% in the cesarean group had levels below 500 ng mL(-1). Bleeding, breastfeeding and heparin prophylaxis did not modify DD levels significantly. CONCLUSION: Using the Vidas DD new assay, our study provides reference intervals for DD in the postpartum period. Using a cut-off at 500 ng mL(-1), DD measurement for ruling out VTE was found to be useful again 4 weeks after delivery.

Adult↗
PubMed2005

Anti-protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation.

Postinfectious purpura fulminans is a rare disease. Varicella is one of the precipitating conditions and we recently observed such a case. The 4-year-old child was found to have a severe transient protein S deficiency. By enzyme-linked immunosorbent assay and surface plasmon resonance we first demonstrated that anti-protein S antibodies were present and also transient. Next we characterized the epitopes against which these antibodies were directed and found that they predominantly recognized the N-terminal part of protein S. Finally we showed by thrombography a transient dramatic hypercoagulable state as a result of thrombin being unregulated by the dynamic protein C inhibitory system: in vitro thrombin generation, in response to a low concentration of tissue factor, was almost insensitive to activated protein C up to 25 nmol L(-1) on day 4 while it was normally sensitive on day 42. For the first time, we demonstrated a temporal relationship between protein S deficiency, antibodies to protein S and hypercoagulability, thus supporting the pathogenic role of these antibodies.

Autoantibodies↗
PubMed2004

Aspirin inhibits endothelial cell activation induced by antiphospholipid antibodies.

BACKGROUND: Antiphospholipid antibodies (APLA) have been shown to activate endothelial cells (EC) in vitro, as documented by an increased expression of tissue factor as well as leukocyte adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin. Currently, treatment of patients with the antiphospholipid syndrome includes aspirin, particularly for women with recurrent fetal loss. OBJECTIVE: The present study was undertaken to investigate whether aspirin interferes with EC activation induced by APLA in vitro. METHODS: IgG from 14 patients with APLA, and suffering from thrombotic complications and/or pregnancy morbidity, and control IgG were tested for their ability to modify the expression of VCAM-1 in human umbilical vein endothelial cells. VCAM-1 antigen was measured by flow cytometry and its mRNA by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Incubation of EC with IgG from most of the patients led to a higher VCAM-1 expression compared with incubation with control IgG. The effect of aspirin was studied for the eight IgG samples that induced a more than 50% increase in VCAM-1. Aspirin (10 mm) treatment of the cells significantly reduced the VCAM-1 response to these APLA. CONCLUSIONS: Our results indicate that besides its antiplatelet properties, aspirin exerts a protective effect towards APLA at the EC level by decreasing leukocyte adhesion molecule expression at the cell surface.

Antibodies, Antiphospholipid↗
PubMed2003

Severe thrombocytopenic purpura due to rubella infection in a patient with systemic lupus erythematosus.

We report the case of a woman suffering from systemic lupus erythematosus who developed a severe thrombocytopenic purpura (platelet count < 1 x 10(9)/l) secondary to rubella infection. The search for antiplatelet antibodies revealed transient circulating anti-GPIIb-IIIa and anti-GPIb-IX platelet antibodies. After a few weeks, bound anti-GPIIb-IIIa antiplatelet antibodies were still detectable and they persisted several months after recovery, probably in relation to a mild autoimmune thrombocytopenia related to systemic lupus erythematosus. To our knowledge, this is the first case report of severe thrombocytopenic purpura due to rubella in an adult with systemic lupus erythematosus.

Adult↗
PubMed2001

TAFI antigen and D-dimer levels during normal pregnancy and at delivery.

We have investigated whether the levels of thrombin-activatable fibrinolysis inhibitor (TAFI) were correlated with D-dimer levels during pregnancy and at delivery. From the 10th week of pregnancy to delivery, 519 samples from 144 women (mean age 29.3 +/- 5, range 19-43) were obtained. We confirm the gradual increase of D-dimer levels, and provide reference intervals for D-dimer measurements throughout normal pregnancy. TAFI levels increased moderately during pregnancy but no inverse correlation with D-dimer levels was observed.

Carrier Proteins↗
PubMed2001

Platelet chemokines and their receptors: what is their relevance to platelet storage and transfusion practice?

The role of platelets as inflammatory cells is demonstrated by the fact that they can release many growth factors and inflammatory mediators, including chemokines, when they are activated. The best known platelet chemokine family members are platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), which are synthesized in megakaryocytes, stored as preformed proteins in alpha-granules and released from activated platelets. However, platelets also contain many other chemokines such as interleukin-8 (IL-8), growth-regulating oncogene-alpha(GRO-alpha), epithelial neutrophil-activating protein 78 (ENA-78), regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), and monocyte chemotactic protein-3 (MCP-3). They also express chemokine receptors such as CCR4, CXCR4, CCR1 and CCR3. Platelet activation is a feature of many inflammatory diseases such as heparin-induced thrombocytopenia, acquired immunodeficiency syndrome, and congestive heart failure. Substantial amounts of PF4, beta-TG and RANTES are released from platelets on activation, which may occur during storage. Although very few data are available on the in vivo effects of transfused chemokines, it has been suggested that the high incidence of adverse reactions often observed after platelet transfusions may be attributed to the chemokines present in the plasma of stored platelet concentrates.

Animals↗
PubMed2001

Deep venous thrombosis and thrombophilia: indications for testing and clinical implications.

In the past 3 decades, numerous biological abnormalities linked with deep venous thrombosis have been described. Among the different possibilities, it is crucial to order tests that can modify the therapeutic attitude towards the patient and/or his family. A combined clinical and laboratory approach taking into account the history of the patient and his family, the prevalence of the defects, and also the accuracy of the tests should allow tailoring a laboratory testing program to each patient. It is essential to keep in mind that the more difficult task is not to perform the tests but to consider who will benefit from testing both for prevention and therapy of venous thromboembolism. This article provides answers to some of these issues. These answers should, however, be considered as tentative and provisional because new findings and study results will certainly modify them in the near future.

Activated Protein C Resistance↗
PubMed2000

Platelet count at term pregnancy: a reappraisal of the threshold.

OBJECTIVE: To assess the safety of a new platelet count threshold for the definition of maternal thrombocytopenia late in pregnancy. METHODS: A platelet count was performed in 6770 pregnant women late in pregnancy and in 6103 of their newborns as well as in a control group of 287 age-matched nonpregnant healthy women. RESULTS: The prevalence of maternal thrombocytopenia (platelet count less than 150 x 10(9)/L) was 11.6%. The mean platelet counts (248 compared with 213 x 10(9)/L) and 2.5th percentile (164 compared with 116 x 10(9)/L) were significantly higher in healthy nonpregnant women than in pregnant women. Among thrombocytopenic pregnant women, 621 (79%) had platelet counts between 116 and 149 x 10(9)/L; none (0%; 95% confidence interval 0, 0.6) had complications related to thrombocytopenia, and none of their newborns had severe thrombocytopenia (platelet count less than 20 x 10(9)/L). CONCLUSION: In healthy pregnant women, a platelet count over 115 x 10(9)/L late in pregnancy does not require further investigation during pregnancy and may be considered a safe threshold.

Adolescent↗
PubMed1999

Maternal antiplatelet antibodies in predicting risk of neonatal thrombocytopenia.

OBJECTIVE: To determine the incidence of maternal antiplatelet antibodies in cases of thrombocytopenia during pregnancy, using the monoclonal antibody-specific immobilization of platelet antigens assay; and to assess the usefulness of this assay for predicting risk of neonatal thrombocytopenia. METHODS: A total of 6770 pregnant women were included in the study, and the monoclonal antibody-specific immobilization of platelet antigens assay was done when platelet counts were less than 150 x 10(9)/L. Platelet counts were determined in 6103 newborns. RESULTS: The incidence of maternal thrombocytopenia was 11.6% (95% confidence interval [CI] 10.8, 12.4). Among newborns, 1.3% (95% CI 0.5, 2.7) born to thrombocytopenic mothers were thrombocytopenic, compared with 0.4% (95% CI 0.2, 0.6) born to nonthrombocytopenic women. Antiplatelet antibodies were detected in 37 (8.6%) of 430 thrombocytopenic women; autoantibodies were detected in 28 cases (circulating or bound to platelets), alloantibodies in eight cases, and an association of alloantibodies and autoantibodies in one case. The positive and negative likelihood ratios for predicting neonatal thrombocytopenia were 4.6 and 0.7, respectively. CONCLUSION: The monoclonal antibody-specific immobilization of platelet antigens assay did not predict the risk of neonatal thrombocytopenia in an unselected population of thrombocytopenic pregnant women.

Adult↗