ABSTRACT
BACKGROUND: Acquired haemophilia A (AHA) is a rare and serious disease, and instances of association with skin diseases have been described. We report a case of postpartum AHA associated with atypical polymorphic eruption of pregnancy (PEP). PATIENTS AND METHODS: Following delivery of her second child, a 27-year-old woman developed a generalised pruritic erythematous papular and vesicular rash in plaques. The diagnosis of pemphigoid gestationis was ruled out on the basis of negative immunopathology results and a diagnosis of PEP was made. Lengthening of activated cephalin time was observed, without correction by addition of control plasma, and prothrombin time was normal. AHA was confirmed by the very low levels of factor VIII and the presence of antifactor VIII antibody. The patient was given intravenous activated recombinant factor VII for epistaxis and gingival bleeding, followed by an infusion of polyvalent immunoglobulins and systemic corticosteroids. Both diseases regressed within a few weeks. DISCUSSION: This case is original in terms of the atypical presentation of AHA associated with severe PEP. AHA was associated with the presence of antifactor VIII Ab. Although the disease generally occurs alone, it has already been reported during pregnancy and the postpartum period, and in association with various forms of dermatosis, including bullous pemphigoid, although to our knowledge, never in association with PEP or pemphigoid gestationis. However, neither the underlying mechanisms of this association of PEP and AHA, which was probably not a chance occurrence, nor the risks of relapse of these conditions during subsequent pregnancies have been elucidated.
Subject(s)
Puerperal Disorders/diagnosis , Skin Diseases, Papulosquamous/diagnosis , Adrenal Cortex Hormones/therapeutic use , Adult , Coagulants/therapeutic use , Factor VIIa/therapeutic use , Female , Hemophilia A/diagnosis , Hemophilia A/drug therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Pregnancy , Puerperal Disorders/drug therapy , Recombinant Proteins/therapeutic use , Skin Diseases, Papulosquamous/drug therapyABSTRACT
Antiplatelet therapy is used to reduce the risk of ischemic events in patients with cardiovascular disease. The balance of benefits and risks of antiplatelet drugs in cardiovascular disease has been evaluated in large-scale randomised trials, however the absolute benefit for an individual patient and a specific platelet-active drug needs further evaluation. Several well-conducted studies have demonstrated a substantial inter-individual variability in platelet responsiveness to drugs. The historical "gold standard" test of platelet function (optical aggregation) has been extensively used for measuring the effect of antiplatelet drugs, but has limitations. New tests developed (i.e. PFA-100®, VerifyNow®) may overcome some of these limitations but they do not correlate well with each other. Despite these unresolved methodological questions, several recent clinical studies, but not all, suggest a significant correlation between antiplatelet resistance status and serious vascular events. In these conditions, laboratory monitoring for antiplatelet therapies raises several questions: (i) the necessity of a consensus regarding the definition of resistance and the relevant test, (ii) the demonstration that biological resistance has clinical significance, and (iii) the clinical impact of individually adjusting the antiplatelet therapy. Therefore, it is not currently appropriate to test patients or to change therapy on the basis of such tests, other than in prospective and adequately powered clinical trials.
Subject(s)
Aspirin/therapeutic use , Cardiovascular Diseases/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pyridines/therapeutic use , Aspirin/adverse effects , Humans , Platelet Aggregation Inhibitors/adverse effects , Pyridines/adverse effectsABSTRACT
The concept of resistance to aspirin and clopidogrel, initially described in the laboratory, has currently been reinforced with recent epidemiological clinical data. One of the elements of particular importance for the cardiologist is the possible participation of this resistance in the process of coronary stent thrombosis, a problem which appeared to be solved early in the 1990s with the introduction of thienopyridines. This complication has however become preoccupying again, particularly when occurring late, notably since the widespread use of biologically active coronary endoprostheses. Nevertheless, the debate continues concerning the usefulness of the biological definition of this concept since we still do not have correctly standardized coherent biological tools that can be used in the clinical setting to detect "resistant" patients. Since there is no real therapeutic strategy which should be applied in the event of resistance, there still is little interest in developing screening methods. But the cardiology community can learn from this concept. We should revisit the principles of revascularization within the framework of the rules of good clinical practice, without speculating about the possible therapeutic finality which might develop should such and such a phenomenon occur.
Subject(s)
Aspirin/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Aspirin/therapeutic use , Cardiology/methods , Clopidogrel , Drug Resistance , Humans , Platelet Aggregation Inhibitors/therapeutic use , Stents , Ticlopidine/analogs & derivatives , Ticlopidine/pharmacologySubject(s)
Blood Platelets/metabolism , Cell Adhesion Molecules/drug effects , Deamino Arginine Vasopressin/pharmacology , Phosphoproteins/drug effects , Cell Adhesion Molecules/metabolism , Deamino Arginine Vasopressin/administration & dosage , Humans , Microfilament Proteins , Phosphoproteins/metabolism , Phosphorylation/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Thrombasthenia/bloodSubject(s)
Drug Monitoring/methods , Flow Cytometry , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Antibodies, Monoclonal , Drug Monitoring/instrumentation , Eptifibatide , Humans , Peptides/blood , Peptides/immunology , Platelet Aggregation Inhibitors/blood , Platelet Aggregation Inhibitors/immunology , Tirofiban , Tyrosine/analogs & derivatives , Tyrosine/blood , Tyrosine/immunologyABSTRACT
Conventional treatment of deep venous thrombosis (DVT) has been based, until recently, on non-fractionated heparin by continuous intravenous infusion in hospital until effective anticoagulation could be obtained by oral anticoagulants introduced early. Low molecular weight heparin (LMWH) seems to be as effective and has a better bio-availability, which means that there are fewer adverse effects. This usage has logically led to the increase in the possibilities of treatment of DVT at home. However, certain precautions are necessary, especially the evaluation of the individual patient's risk with this strategy. This requires multidisciplinary collaboration and the respect of strict rules (precise diagnostic objective, hospital admission at the slightest doubt of pulmonary embolism) to demonstrate the value of ambulatory LMWH therapy which would improve patient comfort and allow early mobilisation.
Subject(s)
Fibrinolytic Agents/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Venous Thrombosis/drug therapy , Fibrinolytic Agents/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Outpatients , Patient Admission , Patient Compliance , Pulmonary Embolism , Quality of Life , Risk FactorsABSTRACT
The PFA-100 (Dade) is a new functional whole blood analyzer, the accuracy and reliability of which have been evaluated in von Willebrand disease and during acetyl salicylate acid therapy. This new test has the advantages of rapidity and simplicity. It may be useful to monitor new antiplatelet agents, such as GPIIb/IIIa receptor antagonists. The objective of this study was to assess the PFA-100 in comparison with aggregometry and with the percentage of blockaded receptors GPIIb/IIIa during and after c7E3 Fab infusion in fifteen patients undergoing PTCA. Our results showed a change of closure time values from normal to abnormal within a small margin of flow cytometric values (60-75% of blockaded receptors), and moreover a variable platelet response to long-term low dose aspirin treatment in agreement with aggregometry. No influence with heparin was observed. In conclusion, this study shows that PFA-100 may be helpful in the decision making for additional antiaggregant therapy before PTCA or in monitoring long-term GPIIb/IIIa receptor antagonist treatment.
Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/pharmacology , Immunoglobulin Fab Fragments/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Platelet Function Tests/instrumentation , Abciximab , Adenosine Diphosphate/pharmacology , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Anticoagulants/adverse effects , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Blood Cell Count , Collagen/pharmacology , Epinephrine/pharmacology , Equipment Design , Female , Hemoglobins/analysis , Hemorrhage/chemically induced , Heparin/adverse effects , Heparin/pharmacology , Heparin/therapeutic use , Humans , Immunoglobulin Fab Fragments/adverse effects , Immunoglobulin Fab Fragments/therapeutic use , Male , Microcomputers , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/bloodABSTRACT
The interactions between leukocytes and endothelial cells have been studied extensively under conditions of ischemia and reperfusion. In contrast, attraction of leukocytes by platelets at the site of damage is poorly understood. This recruitment facilitates inflammation and atherogenesis. Studies performed ex vivo in coronary artery disease show that neutrophil-platelet adhesion increases in unstable angina, coronary angioplasty and coronary artery bypass surgery, in comparison with stable angina. Experimental works have shown the major role of platelet P-selectin in platelet-leukocyte interactions, and of fibrinogen, which is the ligand of both platelets and leukocytes (B2 integrins). Studied performed in anti-GPIIb/IIIa-treated patients demonstrate a modulation, as inhibition, of platelet-leukocyte interactions. This new drug inhibits platelet function and coagulation, and moreover inflammation.
Subject(s)
Blood Platelets/pathology , Chemotaxis, Leukocyte/drug effects , Coronary Disease/blood , Leukocytes/pathology , Platelet Adhesiveness/drug effects , Tyrosine/analogs & derivatives , Abciximab , Angina Pectoris/blood , Angina Pectoris/pathology , Angina, Unstable/blood , Angina, Unstable/pathology , Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Aspirin/pharmacology , Aspirin/therapeutic use , Blood Platelets/drug effects , CD18 Antigens/physiology , Coronary Artery Bypass , Coronary Disease/pathology , Coronary Disease/surgery , Cytokines/physiology , Fibrinogen/physiology , Heparin/pharmacology , Heparin/therapeutic use , Humans , Immunoglobulin Fab Fragments/pharmacology , Immunoglobulin Fab Fragments/therapeutic use , Leukocytes/drug effects , Ligands , Macrophage-1 Antigen/physiology , Membrane Glycoproteins/physiology , Models, Biological , Myocardial Infarction/blood , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardial Infarction/surgery , Neutrophils/drug effects , Neutrophils/pathology , P-Selectin/physiology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Platelet Glycoprotein GPIIb-IIIa Complex/physiology , Thrombospondins/physiology , Tirofiban , Tyrosine/pharmacology , Tyrosine/therapeutic useABSTRACT
Monocytes play a pivotal role in the complex processes of inflammation, immunologic responses and atherothrombosis. Clinical studies essentially reported an increased procoagulant activity in diabetes and coronary disease, suggesting an overexpression of tissue factor. This was further confirmed by the direct measurement of tissue factor on monocyte membrane by flow cytometry. Many receptors can be measured on monocytes by flow cytometry: beta 2 integrins (CD 11 a-b-c/CD 18) involved in adhesion, EPR-1 receptor, receptors for advanced glycation products, urokinase receptor U-PAR. Flow cytometry allows a cell analysis in whole blood. Modern methods allow a standardization of the procedures and a quantification of the number of sites expressed by the cell. However, the respect of preanalytical and analytical conditions is mandatory to obtain reliable data. Besides, clinical studies in diabetes should carefully define the subgroups of patients: type of diabetes, metabolic abnormalities, risk factors, infective complications.
Subject(s)
Diabetes Mellitus/physiopathology , Diabetic Angiopathies/physiopathology , Monocytes/physiology , Diabetes Mellitus/blood , Diabetic Angiopathies/blood , Humans , Inflammation , Integrins/physiologyABSTRACT
Platelet activation and/or platelet reactivity have been reported to be associated with coronary heart disease. Whole blood flow cytometry allows to analyze platelets in their physiological environment, while other assays need platelet separation, susceptible to induce platelet modifications. But flow cytometric assay also have limitations. We studied preanalytical conditions in healthy volunteers, using two monoclonal antibodies directed against CD62 and CD63 (two specific markers of platelet degranulation), and two markers which recognize GPIIb/IIIa activation (PAC1 and bound fibrinogen). Preanalytical requirements were as follow: 1) whole blood samples need antagonists of platelet activation i.e., a mixture of theophylline, adenosine and dipyridamole, since artefactual platelet activation rapidly occurred in citrated whole blood, 2) whole blood should be immediately immunolabeled when samples arrived to laboratory, because fixation did not prevent artefactual time dependent activation, 3) the stability of immunolabeling was determined for each monoclonal antibody: paraformaldehyde as fixative solution was mandatory for both CD62 and CD63, whereas it enhanced bound fibrinogen and PAC1 expression, 4) platelets can be easily identified and gating on a dual scatter (forward scatter x side scatter) dot plot with no specified labeling. The whole blood flow cytometric assay must be standardized in future clinical studies, especially regarding to preanalytical requirements.
Subject(s)
Antigens, CD/blood , Blood Platelets/physiology , Coronary Disease/blood , Platelet Activation , Adenosine/pharmacology , Adenosine Diphosphate/pharmacology , Antigens, CD/analysis , CD40 Ligand , Coronary Disease/diagnosis , Coronary Disease/therapy , Dipyridamole/pharmacology , Humans , In Vitro Techniques , Ligands , Membrane Glycoproteins/pharmacology , Membrane Glycoproteins/physiology , P-Selectin/blood , Platelet Activation/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex/analysis , Platelet Membrane Glycoproteins/analysis , Reference Values , Tetraspanin 30 , Theophylline/pharmacologyABSTRACT
A quantitative flow cytometry assay was used to evaluate the ex vivo kinetics of c7E3 Fab platelet effect in 16 patients undergoing PTCA treated with abciximab and compared with aggregometry assay. Immunolabeling of platelets was directly assessed on whole blood, using in parallel two monoclonal antibodies (Mabs) raised against GPIIIa, Mab1, the binding of which is inhibited by c7E3 Fab, and Mab2, the binding of which is not affected by c7E3 Fab. We found a severe and sustained inhibition of both GPIIb/IIIa receptors and platelet functions. The inter-individual variation in response to abciximab was low. A significant transient increase at H24 and H48 in the binding of Mab2 was found as an unexpected result, and confirmed in vitro. Results demonstrate that flow cytometry is a reliable method in agreement with aggregation. In addition, our results show that it is a standardized tool and a time-saving technique.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Anticoagulants/administration & dosage , Blood Platelets , Immunoglobulin Fab Fragments/administration & dosage , Platelet Glycoprotein GPIIb-IIIa Complex/analysis , Abciximab , Aged , Angioplasty, Balloon, Coronary , Female , Flow Cytometry/methods , Humans , Intraoperative Complications/prevention & control , Male , Middle AgedSubject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/pharmacology , Blood Coagulation Tests/instrumentation , Heparin/pharmacology , Monitoring, Physiologic/instrumentation , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Evaluation Studies as Topic , Heparin/therapeutic use , Humans , Partial Thromboplastin Time , Sensitivity and SpecificityABSTRACT
Polymorphonuclear neutrophils (PMN) and monocytes play a role in vascular diseases. Animal experimental models, using deleukocytation or injection of anti-CD11b-anti-CD18 monoclonal antibodies (inhibition of leukocytic adhesion and of interaction with the endothelial cell) have confirmed this role in the ischemia-reperfusion syndrome and in myocardial infarction. In man, increased production of oxygen radicals, PMN release of elastase, increased monocyte formation of tissue factor (TF) and integrins have been noted in coronary artery disease, in chronic arteriopathy of the lower limbs and in association with vascular risk factors such as diabetes. Pharmacological alteration of leukocyte hyperactivity therefore seems to be justified. Pentoxifylline, used with good effect in arteriopathy of the lower limbs, affects numerous leukocytic functions: diminution in adherence and in PMN production of free radicals, diminution in the formation of TF and cytokines (TNF). Gingkolides reduce leukocytic interactions and platelet activation through an anti-PAF (Platelet Activation Factor) action. Aspirin may interfere with free radicals and inhibit TF formation. alpha-tocopherol blocks the activation, by free radicals, of the transcription factor NF k B. By altering the TNF and IL-1 cytokines, leukocytic activation can be controlled. Other cytokines (IL-4, IL-10) have an immunosuppressive action and reduce the formation of TF. The pharmacological targets are therefore multiple. Their use in vascular diseases is only at a very preliminary stage.
Subject(s)
Leukocytes/physiology , Animals , Cyclic AMP/blood , Free Radicals , Humans , Leukocytes/drug effects , Monocytes/drug effects , Monocytes/physiology , Neutrophils/drug effects , Neutrophils/physiology , Platelet Activating Factor/antagonists & inhibitors , Vascular Diseases/drug therapy , Vascular Diseases/etiologyABSTRACT
Two hundred and sixty-one pregnant women underwent prenatal screening by cordocentesis and/or amniocentesis between 1987 and 1994. The following tests were used: (i) detection of anti-Toxoplasma gondii IgM, IgA, and IgE antibodies by immunocapture and the comparative immunological profile method based on enzyme-linked immunofiltration assay of fetal blood and (ii) direct detection of the parasite in cell culture and by mouse inoculation with fetal blood (FB) and/or amniotic fluid (AF). Of the 31 cases of congenital toxoplasmosis, 24 (77 per cent) were detected prenatally. Overall, the FB and AF inoculation methods were the most effective (50 per cent sensitivity with FB inoculation to mice and/or cell culture and 74 per cent with AF). However, antibody detection in FB was the only positive test in three cases. Of 18 surviving children diagnosed prenatally, only one developed chorioretinitis (9 months of age). Seven newborns (23 per cent) with negative prenatal tests were diagnosed by postnatal laboratory monitoring, but none of these children developed clinical toxoplasmosis. There may have been more false negatives, as only 48 per cent of unaffected children were followed up for at least 12 months. All the tests had a specificity of 100 per cent. Fetal blood sampling has considerable value but also carries some risks and is currently being abandoned in favour of amniocentesis alone with gene amplification and mouse inoculation.
Subject(s)
Amniocentesis , Cordocentesis , Prenatal Diagnosis , Toxoplasmosis, Congenital/diagnosis , Animals , Cell Line , Female , Humans , Mice , Predictive Value of Tests , Pregnancy , Retrospective StudiesSubject(s)
DNA Mutational Analysis/methods , Factor V/analysis , Nucleic Acid Hybridization , Oligonucleotide Probes , Reagent Kits, Diagnostic , Thrombophilia/diagnosis , Alleles , Factor V/genetics , Humans , Point Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Thrombophilia/geneticsABSTRACT
Factor V Leiden mutation was initially detected in thrombophilic patients and relatives by PCR RFLP (Restriction Fragment Length Polymorphism) according to Bertina (1). This technique presents some drawbacks and the current trend is to simplify the diagnosis. We describe a technique of Allele Specific Amplification (ASA) which is optimized in terms of reliability: an additional mismatch in antepenultimate position enables to obtain the same specificity as PCR RFLP. Furthermore, coamplification of internal control warrants an optimal sensitivity. All the PCR have been simplified: the DNA extraction improvement allows to analyse the genotype with only a few microliters of whole blood whatever the anticoagulant and the procedure of preservation (freezing, dried blood spots, storage at +4 degrees C for several days). This technique saves time. Moreover, full automation of the ASA technique may be shortened thanks to the lack of extraction and the positive/negative reading of the PCR signal.