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M Stadler,
U Germing,
K-O Kliche,
K M Josten,
R Kuse,
W-K Hofmann,
H Schrezenmeier,
J Novotny, O Anders,
H Eimermacher,
W Verbeek,
H-H Kreipe,
H Heimpel,
C Aul,
A Ganser
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ABSTRACT: Immunosuppression has recently been proposed for low-risk myelodysplastic syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia) with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41-75). After 1 to 34+ months of follow-up (mean: 15+), four patients experienced complete haematological responses (CR), six good responses (GR) and two minor responses. All CRs and GRs occurred in patients with RA, in whom both horse and rabbit ATG yielded five responses out of 12 (42%). Time to response varied between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1-17+) months; five patients are in continuing response. In all, 23 patients suffered side effects > degrees II WHO (the degree of toxicity encountered according to the internationally accepted WHO toxicity grading); one patient died 2 weeks after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with response were duration of disease and RA subgroup. In our experience, immune-modulating therapy with either horse or rabbit ATG is feasible in patients with RA and short duration of disease.
Leukemia 04/2004; 18(3):460-5. · 9.56 Impact Factor
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ABSTRACT: A 61-year-old man suffering from histologically confirmed amyloidosis associated with coagulation disturbances presented with exercise induced shortness of breath and symptoms of cardiac asthma after four cycles of chemotherapy with melphalan and prednisolone. As a result, treatment with digitoxin was initiated. In addition furosemide and an oral nitrate were administered.
Disparity between electrocardiogram and echocardiographic findings was observed in that, while the electrocardiogram showed loss of 'R wave in precordial leads V(2 - 4), excessive thickening of both left and right ventricular wall was shown in the echocardiogram. Doppler-echocardiography revealed a left ventricular outflow tract obstruction at rest with a peak pressure gradient of 64 mm Hg which rose to 145 mm Hg during Valsalva manoeuvre. Colour Doppler presented a moderate mitral insufficiency and the transmitral Doppler flow studies detected a restrictive left ventricular filling pattern.
Digitalis therapy was stopped because of the outflow tract obstruction complicating cardiac amyloidosis. Cardiac symptoms abated over the following weeks. This improvement was reflected in a significant reduction of the outflow tract gradient, the gradients now being 16 mm Hg under resting conditions and a maximum of 36 mm Hg during the Valsalva manoeuvre. The transmitral Doppler flow pattern showed a pseudonormalisation and the mitral regurgitation regressed nearly completely. The patient was free from cardiac complaints until his sudden death 21 months after the diagnosis of cardiac amyloidosis.
Cardiac amyloidosis can present with left ventricular outflow tract obstruction mimicking hypertrophic obstructive cardiomyopathy. This fact must be borne in mind to avoid therapy with preload-reducing or positive inotropic drugs and especially glycosides.
DMW - Deutsche Medizinische Wochenschrift 09/2001; 126(33):909-12. · 0.53 Impact Factor
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ABSTRACT: Chronic refractory autoimmune thrombocytopenic purpura (AITP) is an autoimmune disorder due to autoantibodies against platelet glycoproteins (GP). Human platelet alloantigenic (HPA) systems are distributed to different platelet GPs. We carried out genotyping of diallelic HPA-1, -2, -3, and -5 systems to clarify potential associations between HPA alleles and the development of chronic refractory AITP.
DNA was isolated from 33 unrelated German patients with chronic refractory AITP and from 80 randomly selected German blood donors to determine the phenotype and allele frequencies for the HPA-1, -2, -3, and -5 systems. Fragments carrying the polymorphic sequences corresponding to those alleles were amplified by the polymerase chain reaction and further characterized by restriction analysis.
Whereas HPA-1, -3, and -5 allele frequencies were identical in 33 patients with chronic refractory AITP and in controls, HPA-2 allele frequencies showed a statistically significant difference (p = 0.017). In our group of patients, the HPA-2a allele frequency was 100%, but HPA-2b was not seen. In contrast, the allele frequency of HPA-2a in the control group was 92% (n = 147), and in HPA-2b it was 8% (n = 13).
This study suggests an association between the HPA-2a allele and chronic refractory AITP. The HPA-2a allele may be involved in the formation of an AITP-specific autoepitope.
Vox Sanguinis 02/1999; 77(3):149-53. · 2.86 Impact Factor
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ABSTRACT: The aim of this study is the registration and the chronological control of inflammatory alterations in the oral mucosa of patients with acute leukaemia under cytostatic treatment. Thirteen patients with acute myeloid leukaemia or acute lymphatic leukaemia were investigated in three oral regions (gingiva, buccal and palatine mucosa) before, during and after cytotoxic drug application for a period of 4-6 weeks by means of exfoliative cytology. Before therapy, patients with leukaemia showed a significant increase in the number of cells from deeper epithelial layers and a significant decrease of the keratinization index for all investigated regions. This is a consequence of the general inflammatory alteration in all mucosal areas. During cytotoxic drug application these findings were modified only for the palatine mucosa. Immediately after the end of cytotoxic drug application only the buccal mucosa showed a slight but not significant tendency for normalization. At this time, only for the palatine mucosa was there a significant tendency toward regression. The study underlines the necessity for intensive dental care of patients with acute leukaemia after treatment with cytotoxic drug, even when the oral mucosa is clinically inconspicuous, as the inflammatory activity may take place subclinically in strongly stressed or vulnerable regions of mucosa.
Mund- Kiefer- und Gesichtschirurgie 12/1997; 1(6):346-8.
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ABSTRACT: We report the unusual complication of focal necrotizing skin lesions accompanied by moderate thrombocytopenia in a female patient undergoing thromboprophylaxis with low-molecular-weight heparin after total knee arthroplasty. Heparin-induced thrombocytopenia was suspected and confirmed using the heparin-induced platelet activation assay. The skin lesions improved gradually after the discontinuation of heparin application. In addition to the description of this exceptionally rare adverse effect of low-molecular-weight heparin, a brief discussion of previously reported cases is provided.
Archives of Orthopaedic and Trauma Surgery 02/1997; 116(6-7):443-5. · 1.37 Impact Factor
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ABSTRACT: The diagnosis of inherited and acquired dysfibrinogenaemia is usually suspected in patients with otherwise unexplained prolonged thrombin time or other tests with thrombin-like enzymes (1). Confirmation of the diagnosis requires discordant results from the investigation of functional fibrinogen and its antigen concentration. However, the issue of the difference between the two results required to confirm dysfibrinogenaemia has rarely been addressed. A difference of at least 0.5 g/l between functional fibrinogen using the method of Clauss and heat precipitation method according to Schulz has been suggested as a prerequisite (1). In the case of acquired dysfibrinogenaemia with an underlying liver disease the discordance should reach at least 1.0 g/l (2). Rodgers and Garr (3) suggested to establish a ratio between fibrinogen function and antigen concentration. In that study plasma from healthy blood donors was investigated using the Clauss method and radial immunodiffusion. We applied this approach to randomly selected patients at the time of admission to a University Hospital Department. Since fibrinogen is one of the major acute phase proteins, the determination of the C-reactive protein (CRP) was included for comparison.
Thrombosis Research 01/1995; 76(6):577-9. · 2.44 Impact Factor
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ABSTRACT: We report on a rare case of spontaneous, life-threatening liver bleeding as a major complication of thrombolysis using short-term, ultrahigh streptokinase in deep venous thrombosis. The event occurred in a female patient (age 40 years) who presented no contraindication to thrombolytic therapy. Intraabdominal bleeding was suspected during intravenous streptokinase infusion. Emergency laparotomy revealed four liter of unclotted blood resulting from two ruptured subcapsular liver haematomas. Local haemostasis was achieved and the integrity of the liver restored. Multiple transfusions of red blood cells, fresh frozen plasma and fibrinogen were given. The postoperative period was uneventful and the patient recovered gradually. The patient could be discharged from the hospital in good health. Diagnostic and therapeutic approaches to this rare complication of thrombolysis are discussed. Additionally, a brief review of previously reported cases is provided.
VASA.: Zeitschrift für Gefässkrankheiten. Journal for vascular diseases 02/1994; 23(4):373-6. · 1.31 Impact Factor
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ABSTRACT: The resonance-thrombogram (RTG) is the result of a new investigation method verifying the clotting process as a whole. It provides a far reaching breakdown of the main factors of coagulation and thus a means for diagnosing and treating coagulation disorders. A special field of application is indication and control of therapy in cases of disseminated intravascular clotting and hyperfibrinolysis in intensive care. Simple operation, relatively quick results and the possibility of rapid diagnosis using the RTG curve appear to make it suitable as a bed-side method of investigating blood coagulation.
Anaesthesiologie und Reanimation 02/1989; 14(4):219-25.
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Stomatologie der DDR 09/1988; 38(8):525-30.
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ABSTRACT: In 64 patients affected with acute leukaemia (51 patients with acute non-lymphatic leukaemia and 13 patients with acute lymphatic leukaemia) extensive investigations of blood coagulation were made during cytostatic therapy. The following conspicuous changes of haemostatasis could be observed in making the diagnosis: Lowered quick value and shortened PTT, increased fibrinogen, fibrinopeptide, A, alpha 1-antitrypsin and alpha 2-macroglobulin, diminished plasminogen and plasma fibrininectin. According to TAD (VP) protocol the induction therapy leads to hypercoagulability which can be recognized by an increase of fibrinopeptide A, coagulating factors and shortening of PTT. During the therapy with L-asparaginasis procoagulatoric as well as thromboprotective coagulating proteins are diminished. A dense laboratory control enables those disturbances of haemotasis caused by disease or therapy to be separated and contributes to preventing complications during the cytostatic induction therapy.
Folia haematologica (Leipzig, Germany: 1928) 02/1988; 115(5):769-80.
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ABSTRACT: In 16 patients affected with acute leukemia (7 patients with acute lymphatic leukemia and 9 patients with acute myeloid leukemia) the resonance thrombogramme was recorded during cytostatic induction therapy, coagulation factor XIII (subunit XIII-A, XIII-S) and further hemostasiological parameters were determined. Subunit XIII-A was lowered to 36%, subunit XIII-S to 65% and the fibrin formation time of the resonance thrombogramme was extended to 9 minutes. There exists a negative correlation between component XIII-A and fibrin formation time r = -0.48 (p less than 0.01). The influence exerted by diminishing factor XIII and fibrin(ogen) splitting products on the fibrin formation time was investigated in in-vitro tests. A diminution of factor XIII below 10% will extend the fibrin formation time to about 10 minutes, an increase of fibrin(ogen) splitting products to 100 micrograms/ml to about 3 minutes.
Folia haematologica (Leipzig, Germany: 1928) 02/1987; 114(5):670-9.
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ABSTRACT: Twice a week plasma (Pl.)-fibronectin was determined quantitatively in the course of disease with immunoelectrophoresis according to Laurell in 12 patients suffered from acute non-lymphoblastic leukemia (ANLL) and in 12 patients affected with acute lymphoblastic leukemia (ALL). At diagnosis Pl.-fibronectin concentration was found to be significantly lowered only in those patients affected with ANLL. During the induction therapy Pl.-Fibronectin could be observed to decline significantly in all patients: in acute non-lymphoblastic leukemia from mean 270 micrograms/ml, s 93 micrograms/ml, to mean 185 micrograms/ml, s 89 micrograms/ml (p less than 0.01), and in acute lymphoblastic leukemia from mean 290 micrograms/ml, s 98 micrograms/ml, to mean 180 micrograms/ml, s 94 micrograms/ml (p less than 0.01). After administering L-asparaginase there is a strong decline of Pl.-fibronectin. Pl.-fibronectin concentration could be observed to be significantly lower in patients without remission in comparison to those with remission. A correlation between Pl.-fibronectin concentration and tumour mass could not be identified.
Folia haematologica (Leipzig, Germany: 1928) 02/1987; 114(3):348-58.
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ABSTRACT: The success of a transfusion of thrombocytes is influenced by numerous factors concerning both the preparation of the platelet concentrate and the recipient. In a long-term substitution of thrombocytes on account of the appearance of immunological and unspecific consumption processes the control of the effectiveness is indicated. The determination of the thrombocyte increment and the resonance thrombography are suitable for this purpose. Fever, sepsis, splenomegaly and haemorrhage cause a diminution of the increase of thrombocytes after transfusion. Isoantibodies have the greatest influence on the shortening of the survival time of transfused thrombocytes. The corrected increase of thrombocytes (CI) 1 hour after the transfusion is lowered under 5.0 Gpt/l (m2). Directives are given for the transfusion and statement of the success of thrombocyte concentrate in patients with leukaemia and malignant tumours.
Zeitschrift für die gesamte innere Medizin und ihre Grenzgebiete 01/1987; 41(23):647-51.
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ABSTRACT: The clinical use of the transfusion of thrombocytes, its indication and problems in the long-term substitution of thrombocytes are explained. Out of the side effects the alloimmunisation against antigens of the HLA-system in the long-term substitution is of greatest importance. A substitution of thrombocytes is indicated in the disturbances of formation. The substitution shall be performed prophylactically in the acute leukaemia and aplasing therapy. When an increased destruction of thrombocytes is existing, other therapy principles are important. Recommendations are given for the prophylactic substitution of thrombocytes. The analysis of the transfusion of 320 concentrates of thrombocytes is reported.
Zeitschrift für die gesamte innere Medizin und ihre Grenzgebiete 12/1986; 41(21):592-5.
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ABSTRACT: 11 patients with deep pelvic and leg vein thrombosis were treated with ultra-high streptokinase infusion, 1.5. 10(6) IE streptokinase per hour over a six hour period. Opening of the vein occlusion was achieved in four cases completely and in five cases partially. The frequency of complications was lower at short-time thrombolysis with ultra-high streptokinase infusion in contrast to long-time thrombolysis. Bleedings did not occur. Because of the slight side effects ultra-high streptokinase infusion is an alternative in the fibrinolytic treatment of risk patients with pelvic and leg vein thrombosis.
Folia haematologica (Leipzig, Germany: 1928) 02/1986; 113(1-2):82-7.
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ABSTRACT: For evaluating the clinical effectiveness of thrombocyte substitution, the resonance thrombogram was registered before and after thrombocyte substitution in 50 patients with acute leukemia and the increase of thrombocytes (corrected increment) determined. Thrombocyte substitution led to a significant diminution of the platelet amplitude (p less than 0.01) and platelet value. The highest value of these alterations of parameters was reached 1 hour after transfusion, it was somewhat lower after 24 hours, yet the initial value was not reached again. Correlations could be found to exist between the platelet amplitude and the corrected thrombocyte increase 1 hour and 24 hours after transfusion. The resonance thrombography enables the successful control of thrombocyte substitution to be made and it is suitable for monitoring hemostasis in severe thrombocytopenia due to production.
Folia haematologica (Leipzig, Germany: 1928) 02/1985; 112(4):587-93.
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ABSTRACT: In a patient with haemophilia A who had a staghorn calculus with recidive haematuria nephrectomy was performed without complications. The operation was preceded by compensation for the haemostasis deficiency by substitution of coagulation factor concentrates. Substitution therapy in connection with operations is discussed and obligatory surgical and haemostaseological preconditions are stated.
Zeitschrift für Urologie und Nephrologie 06/1984; 77(5):295-9.
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ABSTRACT: The serum iron and serum copper level was determined in fifteen patients with lymphogranulomatosis before and during the course of the therapy. While the serum copper was increased in all stages, for the serum iron only in the stages III and IV a tendency to diminution was found. With obtaining the remission a significant increase of the serum iron and a significant decrease of the serum copper developed. The normalization of serum iron and serum copper suggests a remission, the dissociation of the two parameters an activity of the lymphogranulomatosis.
Zeitschrift für die gesamte innere Medizin und ihre Grenzgebiete 05/1984; 39(8):169-72.
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Zentralblatt für Chirurgie 02/1984; 109(8):557-60. · 1.02 Impact Factor
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ABSTRACT: Peripheral blood lymphocytes from healthy subjects and patients with chronic lymphatic leukemia (CLL) were isolated and their subpopulations enriched through formation of spontaneous rosettes with sheep or mouse red blood cells, respectively. Electrophoretic measurements were performed in unseparated as well as in fractionated cell populations. Normal blood lymphocytes showed two clearly distinguishable populations of different electrophoretic mobilities. After separation by SRBC rosette formation the rosette-forming cells could be identified as high mobility cells. CLL lymphocytes showed in most cases an unimodally distributed cytopherogram, the mean electrophoretic mobility being intermediate between the low and high mobility cells of control persons. After separation through mouse erythrocytes rosette formation these cells contained two cell fractions differing in their electrophoretic mobility: a fraction of slower mouse rosette-forming cells and a fraction of the non-MRFC which contained mainly cells of higher mobility that could be identified as enriched T cells. These both fractions showed unimodal distributions. This study shows that CLL lymphocyte subpopulations can be further characterized by surface charge density.
Neoplasma 02/1984; 31(1):57-64. · 1.44 Impact Factor
