Biomedical subjects
Publications and source records attributed to K Lechner.
Explore the source record for details and available documents.
Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.
A 43 year-old female patient was admitted on account of severe dyspnoea of several months' duration and thrombocytopenia. The clinical symptomatology was compatible with pulmonary embolism, but no source of embolization was found and heparin therapy did not lead to clinical improvement. Angiography of the pulmonary artery revealed multiple filling defects. Symptoms improved after treatment with cortisone and so a malignant process was assumed. The patient died from right ventricular failure before the diagnosis could be established. At autopsy a sarcoma of the pulmonary artery, obviously originating from the pulmonary trunk was found. Thrombocytopenia most probably resulted from consumption of platelets by a mechanism corresponding to the Kasabach-Merritt syndrome. The difficulties in the diagnosis of pulmonary artery sarcomas are discussed and the 69 previously published cases are reviewed.
In a prospective study to see whether HLA sensitisation is associated with increased red-blood-cell (RBC) destruction after HLA-incompatible transfusion, chromium-51-labelled RBC survival and site of sequestration were monitored in nine patients in whom HLA antibodies had developed after RBC transfusions. The donors selected were compatible in ABO and RBC-specific antigen systems but mismatched for the HLA antigen in question. Haemolytic transfusion reactions occurred in all four patients who received HLA-B7-incompatible RBC. A direct radioimmune anti-IgG test became positive, Cr51-RBC survival was very short (22.3, 36.9, 41.4, and 44.0 days), and excess sequestration in the spleen was measured. There was a rise in serum lactic dehydrogenase and a fall in haptoglobin. HLA-B7 antibody was detected in the eluate prepared from RBC collected after transfusion. A similar reaction was found in only one further patient, caused by an HLA-A2 incompatibility. No indications of immune-mediated RBC sequestration were discernible after transfusion of HLA-B7-compatible RBC in one of the patients who had shown a reaction with HLA-B7-incompatible blood, nor in any of the other patients who received HLA-B7-compatible RBC. The haemolytic transfusion reactions could not be anticipated by conventional crossmatch procedures, nor by the measurement of the Cr51-RBC survival 1 h after transfusion.
Recent years have seen the rapid development of molecular probes for the detection of defective human genes. These react either directly with the gene in question or with a DNA sequence which lies in close proximity to the gene and which exhibits polymorphism. In the case of haemophilia A two probes were found that belong to the latter category. We have used one of these probes to test its usefulness in the detection of carriers of haemophilia A. For these tests DNA was isolated from blood cells, but can, in principle, be obtained just as easily from other cells or tissues. The results of tests on several families show that the gene technological method is much more precise and sensitive than conventional methods used so far to detect carriers. In all cases a clear assertion was possible as to whether or not the person in question was a carrier of haemophilia A. The method should be applicable to prenatal diagnosis.
Recent data published on the prevalence of inhibitors to factor VIII in hemophiliacs on treatment show great variations, with prevalence rates ranging from 3.6 to 14.2%. We have studied the cumulative risk of inhibitor development in a cohort of 62 patients with hemophilia A. All patients were born after 1960, were natives of the Vienna area, had a factor VIII activity of less than 5%, and were treated at least once. Using the method of Cutler and Ederer, the cumulative risk of inhibitor development was found to be 24% at the age of 25 years. Most inhibitors developed between the ages of 3 and 7 years. The current prevalence of F VIII inhibitors in the group of patients studied is 17.5%. It is concluded that prevalence data underestimate the true risk of inhibitor development.
A 23 years old multiple pretransfused female with severe aplastic anemia (SAA) underwent bone marrow transplantation (BMT). Cyclophosphamide (200 mg/kg) was used for conditioning, donor buffy coat cells were given as rejection prophylaxis. Seven months after BMT regular menses started in the absence of exogenous hormonal manipulation and 21 months after BMT the patient became pregnant. Pregnancy was complicated by mumps in the 14th week. It was terminated at term by cesarean section. The normally developed newborn girl (3,450 gm) presented with a "persistent fetal circulation syndrome". After surgical correction of the patent ductus arteriosus Botalli the girl baby recovered quickly.
Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.
In a double-blind placebo-controlled crossover study, we investigated in seven healthy male volunteers the effect of a low-dose aspirin regimen (35 mg acetylsalicylate per day for 7 days) on the formation of thromboxane A2 (TxA2) and prostacyclin (PGI2) in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time. When subjects were treated with placebo, there was rapid and substantial generation of TxA2 and PGI2 at the site of platelet-vessel wall interaction within the first 2 min after vascular injury. This was reflected by a greater than 100-fold and greater than 10-fold increase in thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in blood obtained from incisions made to determine bleeding time as compared with the corresponding plasma values. Low-dose aspirin caused a significant inhibition of both TxA2 and PGI2 generation in blood sampled from the skin incisions, represented by a 85% and 92% and 81% and 84% inhibition of TxB2 and 6-keto-PGF1 alpha, respectively, as compared with controls. We therefore conclude that rapid activation of both platelet prostaglandin metabolism and vascular PGI2 biosynthesis occurs at the site of platelet-vessel wall interaction, and low-dose aspirin results in a significant inhibition of both platelet and vascular cyclooxygenase activity. Thus, our data fail to confirm the concept of a differential effect of low-dose aspirin on platelet and vascular prostaglandin synthesis in man in vivo.
To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid-associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti-glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3-fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Thirteen cases of posttransfusion purpura (PTP) which were diagnosed in Germany and Austria from 1977-1985 are described. All patients were women with a mean age of 58.6 years (range, 36-77 years). All but one had been pregnant and received blood transfusions 2 to 12 days prior to the onset of PTP. The thrombocytopenic purpura was always severe with a nadir of platelet counts below 10 X 10(9)/l and lasted between 3 and 60 days. All patients recovered from PTP. Optimal therapy consisted of administration of high-dose IgG. Twelve of the 13 patients had developed platelet-specific Zwa antibodies (eight of them together with HLA antibodies), in one Zwa positive individual only HLA antibodies were detectable. Five of six HLA-DR typed patients carried DR3 which is considered an immunogenetic risk factor in PTP. Clinical awareness of this rare, but serious iatrogenic transfusion complication is prerequisite for prompt diagnosis and improved therapy.
Explore the source record for details and available documents.
In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous 111In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of 111In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of 111In-labeled platelets in nonsplenectomized patients suggests "hypersplenism" with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.
Explore the source record for details and available documents.
Chromosome studies were performed in 24 patients who underwent allogeneic bone marrow transplantation (BMT) for severe aplastic anaemia (8), chronic myeloid leukemia (5 in chronic, 2 in accelerated phase and 1 in lymphoid blast crisis), acute myeloid leukemia (6), acute lymphoblastic leukemia in relapse (1) and Hodgkin's disease (1). Donor-cell type engraftment was demonstrated in 21 patients: in all 17 sex-mismatched transplants and - as demonstrated by reconstitution with Ph-negative cell populations - in 4 CML patients with a sex-matched donor. Recipient-type mitoses were seen in the bone marrow of 5 cases (1 SAA, 3 CML, 1 AML) after transplantation. They were only observed on one occasion in patients with SAA (4 of 25 on day 33) and AML (44 of 50 on day 14). Despite the continued demonstration of some Ph-positive mitoses in 3 patients with CML up to day 28, 323 and 451 after BMT, respectively, all surviving CML patients are still in complete haematological and clinical remission. So far the significance of these cytogenetically abnormal persisting host cells remains unknown.