Paul Capel

Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease

We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16307 men (age, 35-59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03-1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease.

Low response to high‐dose intravenous immunoglobulin in the treatment of acquired factor VIII inhibitor

Prednisone is the classic first‐line therapy to suppress an acquired factor VIII inhibitor and may achieve complete remission in about 30% of patients. More recently, promising results have been reported with high‐dose intravenous immunoglobulin (IVIg). However, after an extensive review of the literature, we found only three complete remissions (12%) among the 26 assessable patients treated by IVIg. These data are in agreement with the low response to IVIg that we experienced in our series of patients. This study suggests that steroids should still be preferred to IVIg, an expansive therapy, to suppress an acquired factor VIII inhibitor.

IL‐5 in post‐traumatic eosinophilic pleural effusion

Thoracic trauma or pneumothorax can result in pleural fluid eosinophilia. In this study we investigated the role of the eosinophilopoietic cytokine IL‐5 in three cases of post‐traumatic eosinophilic pleural effusions (EPE). Using a specific immunoenzymatic assay, significant levels of IL‐5 were found in EPE (range 100–3000 pg/ml), while IL‐5 was undetectable (<25 pg/ml) in corresponding serum samples and in non‐eosinophilic pleural fluids. IL‐5 present in pleural fluids was found bioactive in a proiiferative assay using a mouse CTLL‐2 cell line transfected with the cDNA corresponding to the a chain of the human IL‐5 receptor. Using a reverse polymerase chain reaction (PCR) method, we found IL‐5 mRNA expression within pleural mononuclear cells from patients with EPE, but not in corresponding peripheral blood mononuclear cells (PBMC), confirming that IL‐5 is synthesized locally in the pleural cavity. In the two cases in which pleural CD4+ cells were purified, these cells were identified as the major source of IL‐5. Taken together, these data indicate that the development of post‐traumatic EPE is related to a local secretion of IL‐5 by CD4+ cells present in the pleural cavity.

Evaluation of two D-Dimer assays in the diagnosis of venous thromboembolism.

A qualitative (Instantia) and a quantitative (VIDAS D-Dimer) D-Dimer test have been evaluated and compared with an ELISA method (Asserachrom D-D) in a population of 74 patients suspected of presenting a deep vein thrombosis. Among the thirty-two patients presenting a deep vein thrombosis on phlebography, there were 16 (50%) proximal vein thrombosis and 16 (50%) distal vein thrombosis. Sensitivity and negative predictive value for proximal thrombosis were 100% in all three tests. For distal vein thrombosis, sensitivity and negative predictive value were respectively 81% and 81% for Asserachrom D-DI 75% and 76% for VIDAS D-Dimer and 63% and 82% for Instantia. In conclusion, this study shows that these D-Di assays are a useful tool to exclude proximal vein thrombosis, at least for patients who are not under anticoagulant therapy.

CHEMOTHERAPY OF ACUTE MYELOBLASTIC LEUKEMIA IN AN HIV CARRIER

To the Editor: Myelodysplasia is known to occur with an increased frequency in HIV + patients; lymphoproliferative neoplasms mostly of the B-cell lineage have also been frequently described (1). However, myeloblastic leukemias are not frequently described in HIVinfected patients we found 2 cases in the literature (2, 3), neither addressing the problem of treatment of those malignancies in this particular setting. Our patient is a 53-yr-old white male homosexual, known to have anti-HIV antibodies since November 1989. Regular checkups since were unremarkable, except for a CD4 count consistently above lOOO/ mm3, the presence of HIV antibodies on Western blot; clinical status was perfect. On 8/10/92 he still had no complaints, physical examination showed a consistently obese abdomen; spleen was not palpated. White blood cell count was 80000/mm3 with 3000 platelets/mm3 and 3% neutrophils. The 5 1 % blasts were myeloperoxidaseand Sudan black-positive. Positive findings included a 15 cm x 12 cm x 6 m spleen on echography and 7 decayed teeth. Serum lysozyme was 16 pg/mm3 (upper limit of normal 13 pg/mm3). The patient was well and apyretic. Bone marrow examination showed numerous cells with 5 1.2% myeloblasts (peroxidaseand Sudan black-positive, CD34 + , CD 13 + and CD 15 + ). There were 35 % eosinophils. Megakaryocytes were absent. Karyotype the blast cells showed was 46 XY with inv (16) (p13q22) typical of FAB ANLL M4eo (3). Chemotherapy was instituted consisting of idarubicin 12 mg/m2 on d 1 to 3, and cytarabine 200 mg/ m’ on d 1 to 7; blasts were undetectable in peripheral blood by d 5 ; aplasia also occurred. The patient was discharged after 3 wk; 1 wk later, consolidation was given (idarubicin 12mg/m2 d 1, cytarabine 200 mg/m2 d 1 to 7). Bone marrow control showed no blasts 3 wk later (on 17/12/92). No further chemotherapy was administered, monthly follow-up visits were satisfactory; CD4 levels were 1000/mm3 on 13/4/93. To our knowledge this is the first report of successful treatment of myeloblastic leukemia in a carrier of HIV. One patient with a hybrid leukemia (B-cell ALL and FAB M4 ANLL) has been described who died before any attempt at treatment (2). We believe the FAB M4 ANLL presented by our patient has no direct connection with his HIV status. Of interest is the fact that p24 was never isolated in the patient’s serum, nor were infectious viral particles detected in coculture assays (patient’s mononuclear cells cultured with blood donor lymphocytes). Chemotherapy thus did not seem to enhance HIV infection; since idarubicin as well as cytarabine (which is a pyrimidine analogue) inhibit DNA synthesis, we cannot exclude that viral replication was suppressed as well.

Effects of aprotinin on blood loss, heparin monitoring tests, and heparin doses in patients undergoing coronary artery bypass surgery

OBJECTIVES Evaluation of the effect of aprotinin on heparin monitoring tests, on heparin doses, and on perioperative blood loss in patients undergoing coronary artery bypass grafting. DESIGN Randomized, prospective open study. SETTING The study was performed in the departments of Anaesthesiology and Haematology of the Erasme University Hospital, Brussels. PARTICIPANTS Twenty-six patients undergoing primary coronary artery bypass grafting. INTERVENTIONS Twelve patients received aprotinin, and 14 received no treatment. MEASUREMENT AND MAIN RESULTS Aprotinin significantly reduced blood loss during coronary artery bypass surgery and was associated with a slight reduction in the amount of heparin administered. Activated coagulation time and activated partial thromboplastin time were prolonged by the addition of aprotinin. Activated coagulation time and activated partial thromboplastin time were poorly correlated with heparin assays. On the other hand, two other clotting tests designed to monitor heparin therapy, namely Titrarine (Stago, Asnière, France) and Heptest (Haemachem, St. Louis, MO), gave very good correlation with amidolytic heparin assays and can be used during extracorporeal circulation. Thrombin time showed a good correlation with amidolytic heparin assays after protamine administration and can be useful to detect residual heparin after heparin neutralization by protamine.

Simplification of the blood stem cell transplantation (BSCT) procedure : large volume apheresis and uncontrolled rate cryopreservation at −80°C

Abstract: Very high‐dose chemotherapy with autologous blood stem cell (BSC) rescue becomes more and more widely performed. In order to simplify the technique, a large volume apheresis programme combined with an uncontrolled rate cryopreservation at –80°C was developed. Twenty‐six patients suffering from multiple myeloma (n = 8), non‐Hodgkins lymphoma (n = 7), dysgerminoma (n = 4), breast cancer (n = 3), Hodgkins disease (n = 2), acute lymphoblastic leukaemia (n = 1) and acute myelocytic leukaemia (n = 1) were autografted after a classical high‐dose chemotherapy regimen. A single large volume apheresis was sufficient to obtain the threshold value of CD34+ BSC in 24/26 transplantations. The haematological recovery was favourably comparable with the previously published data obtained with controlled rate frozen BSC: median time to granulocytes > 1000/μL and to a self‐supporting platelet count > 20,000/μL, respectively, 10.5 and 12 d. The treatment‐related mortality was confined to 1/26 BSCT. These results indicate that this easy and cost‐saving policy of BSCT is efficacious and safe: sustained long‐term haematopoiesis, reduced morbidity and mortality were observed.

Morphologic and phenotypic changes of the leukemic cells in a case of marginal zone B-cell lymphoma

Abstract A particular case of marginal zone B-cell lymphoma (MZBCL) presenting with leukemic lymphocytes is reported. In the present observation, the leukemic cells not only displayed a remarkable morphological fluctuation but also had an unusual phenotype, changing with time. These phenotypic features, which have been functionally investigated by in vitro assays, might simply reflect an activation state depending on the microenvironment. Because of its disconcerting similarities with hairy cell leukemia (HCL) and splenic lymphoma with villous lymphocytes (SLVL), this case relaunches the debate about whether close relationships might exist between the splenic marginal zone, SLVL and HCL.

Comparative study of antiphospholipid antibody detection in eleven Belgian laboratories

Twenty-six plasma samples have been sent to 11 different Belgian laboratories in order to detect the presence of antiphospholipid antibodies, either by immunological methods and/or by coagulation tests. A good concordance between laboratories was observed for coagulation tests. Laboratories using detection tests and performing mixing procedures and neutralisation procedures displayed the highest sensitivity as compared with laboratories which did not perform one of these two latter procedures. The concordance between laboratories for the immunological methods was much worse as compared with coagulation tests. This may be attributable either to an intrinsic problem of the immunological tests or to a selection bias due the fact that the plasmas used in this study were selected in coagulation laboratories only where the chance to find a lupus anticoagulant positive/ELISA antiphospholipid negative sample is high.

Quality control in haemostasis

Laboratory investigation of the haemostatic system deserves particular procedures in the quality control of analytical variables as well as preanalytical variables. This paper reviews the precautions that have to be taken in the blood prelevement, the transport of the tubes and the performance of the laboratory tests aimed to investigate the haemostatic system in order to obtain reliable results.