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Biomedical subjects

A von Felten

Publications and source records attributed to A von Felten.

At least 19 recordsLinked to original sources

Ankylosing spondylitis and sarcoidosis--coincidence or association? Case report and review of the literature.

We report a 25-year-old woman presenting with sarcoidosis and bilateral sacroiliitis. Her sarcoidosis related symptoms (malaise, cough and dyspnoea) improved dramatically under treatment with steroids but severe back pain persisted. Only seven similar cases have been described over the last 40 years and the question of a possible association between the two diseases has been raised. However, prevalence data from the literature and the apparent lack of genetic links are better arguments for coincidence than for association.

Adult

[Prevention of venous thromboembolism with heparin in risk patients during pregnancy: monitoring by measuring thrombin-antithrombin III complex].

Women at high risk for thromboembolism deserve prophylactic treatment with heparin in the course of pregnancy. Since activation of the coagulation system is associated with an increase of TAT complexes which may well precede the clinical thrombosis, this parameter was used to determine start as well as dosage of the heparin prophylaxis. Thereby, the increase of TAT complexes during a normal pregnancy without thrombolic events had to be taken in account. 43 pregnancies of 40 patients who had already suffered from thrombotic events before pregnancy or had a positive family history were monitored by this method; in none of them any thromboembolic complication occurred. Duration of treatment and maximal amount of heparin showed wide individual variations and could not be predicted by clinical criteria. However, the total dose of heparin necessary was in many patients far below of what is usually administered, thus reducing the risk of heparin-induced osteoporosis and of local allergic reactions.

Antithrombin III

Reduction and elimination of systemic heparinization during cardiopulmonary bypass.

After extensive experimental evaluation, heparin-coated perfusion equipment was clinically evaluated with low or no systemic heparinization in three different groups of patients (n = 47). In group 1, resection of descending thoracic aortic aneurysms (n = 24) was performed with heparin-coated equipment used for left heart bypass (n = 12) or partial cardiopulmonary bypass (n = 12) for proximal unloading and distal protection (heparin 5000 IU, autotransfusion). All devices remained functional throughout the procedures and no systemic emboli were detected. The sole death (1 of 24, 4%) occurred in a patient with ruptured thoracoabdominal aortic aneurysm requiring operation in extremis. Paraparesis with spontaneous recovery occurred in one patient (1 of 24, 4%). In group 2, coronary artery revascularization randomized for low (activated clotting time greater than 180 seconds) versus full (activated clotting time greater than 480 seconds) systemic heparinization was prospectively analyzed in 22 patients. All patients recovered without sequelae, and no myocardial infarction was diagnosed. Low dose of heparin (8041 +/- 1270 IU versus 52,500 +/- 17,100 IU; p less than 0.0005) resulted in reduced protamine requirements (7875 +/- 1918 IU versus 31,400 +/- 14,000 IU; p less than 0.0005), reduced blood loss (831 +/- 373 ml versus 2345 +/- 1815 ml; p less than 0.01), reduced transfusion requirements of homologous blood products (281 +/- 415 ml versus 2731 +/- 2258 ml; p less than 0.001), and less patients transfused (5 of 12 versus 10 of 10; p less than 0.05). Lower D-dimer levels in the group perfused with low systemic heparinization (0.50 +/- 0.43 mg/L versus 1.08 +/- 0.59 mg/L; p less than 0.05) were attributed to the absence of cardiotomy suction in this group. In group 3, rewarming in accidental hypothermia by cardiopulmonary bypass was successfully performed without systemic heparinization in a patient with hypothermic cardiac arrest (23.3 degrees C) and intracranial trauma. We conclude that systemic heparinization for clinical cardiopulmonary bypass can be reduced and eliminated in selected patients if perfusion equipment with improved biocompatibility is used. Bypass-induced morbidity can be reduced.

Aged

Successful allogeneic bone marrow retransplantation with the same donor after graft rejection: application of a modified conditioning regimen.

A 26-year-old man with severe aplastic anemia was treated with high-dose Cyclophosphamide followed by the infusion of bone marrow cells from his HLA-identical sister. After initial intake of the graft, rejection ensued by day 46 which was followed by a permanent complete aplasia. After 4 months, bone marrow retransplantation with the same donor was attempted after a more intensive conditioning regimen. This led to permanent engraftment with rapid normalization of the blood counts lasting now for over 12 months. The patient has since remained in excellent clinical condition without signs of graft-versus-host disease.

Adult

Thrombocytopenic episodes in patients with well-functioning renal allografts. Inverse relationship between platelet count and platelet size pointing to intermittent platelet destruction.

20 out of 50 patients with well-funcioning renal allograft displayed at least one platelet count below 110 X 10(9)/1 (mean -2 SD of controls). For estimation of platelet production during thrombocytopenic episodes, the percentage of large platelets in the peripheral blood was determined which revealed an inverse relationship (p less than 0.01) to the platelet count, indicating that these thrombocytopenias were due to increased platelet consumption. Immunosuppressive treatment as well as rejection processes could be excluded as major pathogenetic factors whereas anti-platelet autoantibodies may contribute to this phenomenon.

Autoantibodies

[Granulocyte substitution in febrile leukemia patients with bone marrow aplasia. 1. Results of a prospective study].

A prospective, randomized study was performed in aplastic, granulocytopenic, infected patients with acute leukemia during induction therapy. 12 patients received antibiotics alone, and 13 received antibiotics plus 1.7-14.7 X 10(10) (MEAN 6.6 X 10(10) granulocytes by 1-5 (mean 2.7) daily transfusions. In 10 of 12 controls the infection resolved and remission was achieved with granulocyte counts greater than 500/mm3 15 +/- 9 days after randomization. In the transfused patients, infection was brought under control in 10 out of 13 and remission was achieved with granulocyte counts greater than 500/mm3 25+/- 11 days after randomization. Only one death due to infection was observed (6 days after randomization, control).

Anemia, Aplastic

[Thrombocyte migration test as a sensitive tolerance test before platelet substitution (proceedings)].

Thrombocytopenic patients refractory to random-donor platelet support can usually be substituted by platelets obtained from donors identical with respect to HLA-A and -B antigens [1]. Since such "full-house" identity is rarely available, reliable cross-match tests (CM) are needed in order to pick out donors compatible in spite of HLA non-identity. By use of the thrombocyte migration test (TMT), DUQUESNOY et al. have shown that antiplatelet antibodies may exert an inhibitory effect on platelet migration. Therefore, we have explored this test system for its efficiency as CM compared with the "long-time" lymphocyte cytotoxicity test (LLT). Of 8 sera from polysensitized patients, serial dilutions were performed and simultaneously tested by TMT and LLT with cells obtained from the same control individuals. The sensitivity of TMT exceeded LLT by 2-4 dilution steps in all sera tested. Moreover, 9 patients with incompatible transfusion responses to single-donor platelets in spite of negative LLT had the following results in TMT with pre-transfusion sera: 5 positive (i.e. migration inhibition), 1 negative: enhanced migration was observed 3 times. This phenomenon of enhancement remains to be clarified, since low titers of anti-HLA-antibodies do not cause enhanced platelet migration. Repeated transfusion of platelets obtained from the same donor may cause antibody production against leukocytic antigen not shared by platelets, leading to "false-positive" LLT. 2 patients were successfully substituted with platelets from HLA/MLC-identical siblings in spite of positive LLT, but with negative TMT; in 2 cases with unrelated HLA-A and -B identical donors, TMT results were inconsistent.

Blood Platelets

[Drug induced agranulocytosis. Improved prognosis due to better supportive care].

A retrospective study of 61 episodes of agranulocytosis observed in 56 patients between 1958 and 1977 is reported. The diagnosis was based on peripheral granulocyte counts below 500/mm3 and further documented by bone marrow analysis. The aim of this study was to determine whether the new guidelines for supportive care introduced in January 1973 led to an improvement in overall prognosis in this disease. Therefore, the patients were divided into two groups: the first group included 39 episodes of agranulocytosis observed between 1958-1972 and the second group 22 episodes observed between 1973-1977. Standard supportive care administered in the latter group included reverse isolation (hand-disinfection and gown-change before patient contact, conventional hospital single room), the immediate initiation of an appropriate combination of antibiotics in infectious states and additional granulocyte transfusions in selected cases. The two groups compared were similar as to the extent of neutropenia and the frequency of severe infectious complications. On the other hand, patients of the first group showed more advanced recovery of myelopoiesis as compared to the second group at the time of hospital admission. Death due to infection was observed in 36% of episodes in the first group, but only in 9% in the second group. The supportive care introduced in 1973 thus appears to improve the prognosis of agranulocytosis to a substantial extent.

Agranulocytosis

[Acute iridocyclitis, ankylosing spondylitis (Bechterew) and congenital tissue antigens (author's transl)].

The tiysue antigen HLA-B27 was present in 92.6% of 95 Swiss patients with classical ankylosing spondylitis. This tissue antigen is present in only 7.7% of healthy Swiss blood donors. 36% of all patients had one or several acute attacks of anterior uveitis. This usually follows the onset of joint symptoms. In 4% of the 95 patients the iritis was the first symptom. The combination of acute uveitis and ankylosing spondylitis with the tissue antigen HLA-B27 indicates that not only the spondylitis, but also the uveitis is in many cases genetically determined.

Acute Disease

[Anti-phospholipid antibodies as a cause of immunologic thrombopenia and thrombopathies].

The simultaneous occurrence of platelet antibodies (ab) and a circulating "antithromboplastic" anticoagulant in a patient with thrombocytopenia led to the hypothesis that antiphospholipid ab may be causing both phenomena. Of 55 sera obtained from thrombocytopenic patients exhibiting a positive microtest for complement fixation (CFT) with platelets, 37 also gave positive results with highly purified phospholipids (Phl) used as antigen. In order to further evaluate the role of Phl, 40 different liposome suspensions obtained by sonication of various mixtures of Phl (with/without addition of cholesterol) were tested as antigen in the CFT with 11 selected sera, and as platelet factor 3 (PF3) reagent in the partial thromboplastin time test with normal plasma. Eight liposome preparations with PF3 activity (all containing phosphatidyl-serine) were equally active as antigen (ag) in the CFT. Liposomes composed of phosphatidyl-ethanolamine and sphingomyeline delivered ag-activity only. Since the two substances are accessible components of the outer membrane surface of thrombocytes, anti-Phl-ab may well bind to platelets in vivo, causing thrombocytopenia. Coagulation-inhibiting activity of these ab could be directly demonstrated in a PF3-test system (thrombocytopathy caused by PF3 inhibition). The identity of antithromboplastic anticoagulant and anti-Phl-ab was further substantiated by immunoabsorption, since both activities were simultaneously eliminated from the sera with a Phl-charcoal adsorbent.

Antibodies

[Substitution ofpolysensitized patients with platelets from HL-A typed single donors].

80 platelet transfusions from 38 different "full-house" HLA-typed single donors (10 siblings, 28 unrelated persons) were given to 14 thrombocytopenic patients refractory to platelets from random donors. The transfusions resulted in increased platelet increments, provided that the donor had no additional HLA-specificities whatsoever. In 14 out of 19 situations of not-identity between donor and recipient and with poor posttransfusion platelet increments, lymphocytotoxicity tests (incubation of 180 min at room temperature) were positive. This test therefore appears to be a useful tool in predicting the outcome of the transfusions. Granulocytotoxicity tests were positive in 4 HLA-identical donor-recipient pairs. Although severe transfusion reactions were observed, no detrimental influence on platelet increments could be found.

Blood Platelets

[Anti-thrombocyte antibodies].

1. There are two possible ways in which platelets may be involved in immune reactions: a) as target cells for antiplatelet antibodies, and b) as receptor cells for circulating antigen-antibody complexes. Since most of the clinical tests used to detect "antiplatelet antibodies" are incapable of discriminating between the two mechanisms, thrombocytopenia in many autoimmune diseases with "antiplatelet antibodies" may well be caused by immune complexes. 2. Immune reactions involving platelets do not always lead to thrombocytopenia. A moderate acceleration of platelet destruction can easily be compensated by increased production: this situation corresponds to a "compensated thrombocytolytic state". Evidence is also presented for immunologically induced functional platelet defects of "immunologic thrombocytopathy.

Agranulocytosis