W Kirschstein

Universität Heidelberg, Heidelberg, Baden-Wuerttemberg, Germany

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Publications (15)24.47 Total impact

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    ABSTRACT: The molecular basis of hypofibrinogenaemia was investigated in a 34-year-old woman and her 10-year-old daughter. DNA sequencing revealed a single heterozygous GCC-->GTC transition in exon 8 of the fibrinogen gamma ?gene in both subjects, predicting a novel gamma289 Ala-->Val substitution. Examination of fibrinogen gamma ?chains by electrospray ionization mass spectrometry failed to detect the variant chain in plasma fibrinogen. Further evidence for its non-expression came from tryptic peptide mapping. The mutation predicts a mass increase of 28 Da in peptide T32, but only the normal (M + 2H) ion was detected at 1418 m/z in the proposita. Our finding that gamma289 is an important determinant of plasma fibrinogen levels highlights the role of mutational analysis in defining structurally important regions of the fibrinogen molecule. This case suggests that the highly conserved Ala(289) is important in maintaining structure of the "a" polymerization site via hydrogen bonding to Thr(371).
    Thrombosis and Haemostasis 01/2005; 92(6):1291-5. · 5.76 Impact Factor
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    ABSTRACT: In recent years it has become clear that the molecular investigation of hypofibrinogenemia provides unique insight into regions of the fibrinogen molecule that are important in molecular assembly, secretion and stability. To investigate a case of hypofibrinogenemia at the molecular level. PATIENTS and The study was conducted on a 37-year-old woman from Mannheim, Germany, who had an antigenic plasma fibrinogen concentration of 0.86 g L(-1). Mutation screening was performed by DNA sequencing and the effect of the identified mutation was investigated at the protein level. Analysis of exon 8 of the fibrinogen gamma gene identified a heterozygous CAT-->TAT transition at codon 307. This novel His-->Tyr substitution was not detected when plasma fibrinogen was analyzed by electrospray ionization mass spectrometry. The mutation predicts a mass increase of 26 Da in the gamma chain, but purified gamma chains had a normal mass, indicating non-expression of the gamma(Tyr307) chain in plasma fibrinogen. This work reports a novel gamma307 His-->Tyr mutation (fibrinogen Mannheim II) that causes hypofibrinogenemia. Crystal structures show that His307 is located immediately adjacent to three residues that have been implicated in fibrin polymerization at the D:D interface. However, the histidine residue appears critical in maintaining structure of the fibrinogen gammaD domain, rather than in determining function.
    Journal of Thrombosis and Haemostasis 01/2005; 2(12):2194-9. · 5.55 Impact Factor
  • Thrombosis and Haemostasis 01/2004; · 5.76 Impact Factor
  • M Baur, U Staedt, W Kirschstein, D L Heene
    Der Internist 10/1997; 38(9):854-7. · 0.27 Impact Factor
  • Zeitschrift für Herz- Thorax- und Gefäßchirurgie 10/1997; 11(5).
  • M. Baur, U. Staedt, W. Kirschstein, D. L. Heene
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    ABSTRACT: Ein 70jähriger Patient wurde mit progredienter Dysphasie, Desorientiertheit und Somnolenz stationär aufgenommen. Richtungsweisende Befunde ergaben sich aus der körperlichen Untersuchung, dem EKG, dem Röntgen-Thorax und dem Schädel-CT sowie den routinemäßig erhobenen Laborparametern nicht. Eine ausgeprägte metabolische Azidose ließ daher bei Ausschluß einer Urämie und Ketoazidose an eine Intoxikation denken. Hierbei kommt insbesondere eine Kohlenmonoxid-, Salizylat-, Methanol- oder, wie im vorliegenden Falle eine Äthylenglykol-Vergiftung in Frage. Therapeutisch müssen dabei neben einer primären Giftelimination eine rasche Zufuhr von Äthanol, ein Azidose- und Elektrolytausgleich sowie insbesondere eine baldige Hämodialyse durchgeführt werden.
    Der Internist 09/1997; 38(9):854-857. · 0.27 Impact Factor
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    ABSTRACT: Die pulmonale Thrombendarteriektomie ist vor einer Lungentransplantation die wichtigste Therapieform für Patienten mit persistierender pulmonaler Hypertonie nach einer Lungenembolie. Die vorgestellte Kasuistik berichtet über eine junge Patientin mit juvenilem Diabetes mellitus. Während eines stationären Aufenthaltes kam es katheterassozüert zu einer Staphylokokkensepsis mit Trikuspidalklappenendokarditis und nachfolgender ausgedehnter Lungenembolie. Vier Jahre nach dem Ereignis wurde aufgrund einer zunehmend verminderten Belastbarkeit wegen höhergradiger pulmonaler Hypertonie eine erfolgreich verlaufende pulmonale Thrombendarteriektomie durchgeführt. Im Langzeitverlauf kam es zu einer deutlichen Besserung der Belastbarkeit und Lebensqualität, die Patientin ist wieder voll arbeitsfähig und konnte nach unproblematischer Gravidität ein gesundes Mädchen gebären. Pulmonary thromboendarterectomy presents an efficient option of treatment for patients with chronic pulmonary hypertension after pulmonary thromboembolism. We report about the case of a young lady with juvenile diabetes mellitus. During a hospital stay she suffered a catheter-associated endocarditis of the tricuspid valve and pulmonary thromboembolism. Four years after the event she had a lower exercise tolerance due to pulmonary hypertension and underwent a pulmonary thromboendarterectomy. During long time follow-up her exercise tolerance normalized and she had an uneventful delivery of a girl.
    Zeitschrift für Herz- Thorax- und Gefäßchirurgie 01/1997; 11(5):227-231.
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    ABSTRACT: Coagulation studies were performed in a patient who had been bitten by a snake of the species Bothrops neuwiedi. The patient presented with hemorrhagic necrosis at the envenomization site and considerable bleeding from venous puncture sites. He developed a severe defibrination syndrome with a clottable fibrinogen level of approximately 0.1 g/l. Fibrinogen was not measurable by clotting time assay. Fibrin degradation products were greatly elevated. Treatment with antivenom caused an anaphylactic reaction within ten minutes and serum sickness after three days. In vitro experiments revealed that B. neuwiedi venom directly activates Factors II and X, but does not activate Factor XIII. In vivo consumption of Factor XIII after B. neuwiedi envenomization is ascribed to the action of Factor IIa. At low venom concentrations clotting is initiated by activation of prothrombin by the venom either directly or via Factor X activation. Treatment with heparin might be beneficial in coagulopathy secondary to snake bite by reducing circulating active thrombin. The venom contains thrombin-like proteases which cause slow clotting of fibrinogen, and plasmin-like components causing further proteolysis of fibrinogen and fibrin. Antivenom has no effect on the proteolytic action of the snake venom. The in vivo effects of antivenom are presumably caused by acceleration of the elimination of venom components from the circulation. Intravenous administration of antivenom caused normalization of blood coagulation parameters within 48 h.
    Blut 01/1991; 61(6):369-74.
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    ABSTRACT: To assess the role of the fibrinolytic system in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we determined the components of this system in a retrospective study, including 16 patients with restenosis (gr. A) and 19 patients with long-term success (gr. B). In both groups at baseline fibrinolytic activity (FA) is unchanged, whereas tissue plasminogen activator antigen (tPA-Ag) is significantly increased (gr. A: 147.0%; gr. B: 139.8%; p less than 0.01). Fibrinolytic capacity (FC) and tPA-Ag release are significantly reduced in the restenosis group (FC: 46.5%, p less than 0.05; tPA-Ag release: 48.3%, p less than 0.01) compared to normal controls as well as to gr. B (FC: 84.3%, p less than 0.05; tPA-Ag release: 79.0%, p less than 0.05). Relating to the contact activation system, F XII (79.5%, p less than 0.05) is significantly, and F XI (82.3%) is clearly reduced in gr. A. Protein C (PC) is significantly elevated in gr. B (117.5%, p less than 0.05). There is a negative correlation between plasminogen activator inhibitor (PAI 1) and HDL-cholesterol (r = 0.37, p less than 0.05). It appears, that there is a typical pattern of defective fibrinolysis in patients with restenosis after PTCA and that this might be a pathogenetic factor in the development of restenosis.
    Thrombosis and Haemostasis 10/1989; 62(2):772-5. · 5.76 Impact Factor
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    ABSTRACT: A 43-year-old man had severe upper abdominal pain and weight loss of 8 kg for over three months. He underwent a laparotomy because, computed tomography having revealed numerous mesenteric and para-aortic lymph nodes, a malignant lymphoma was suspected. Histological examination of a mesenteric lymph node demonstrated exclusively extraintestinal Whipple's disease. The symptoms completely disappeared after the administration of 1.2 mega U penicillin G and 1 g streptomycin daily for 14 days, followed by twice daily 160 mg trimethoprim and 800 mg sulphamethoxazole.
    DMW - Deutsche Medizinische Wochenschrift 08/1989; 114(28-29):1107-9. · 0.55 Impact Factor
  • VASA. Supplementum 02/1989; 27:253-4.
  • DMW - Deutsche Medizinische Wochenschrift 01/1989; 114:1107-1109. · 0.55 Impact Factor
    Fibrinolysis & Proteolysis - FIBRINOLYSIS PROTEOLYSIS. 01/1988; 2.
  • D L Heene, W Kirschstein, C E Dempfle
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    ABSTRACT: The major constituents of the hemostatic potential, i.e., platelets and the plasma factors of coagulation and fibrinolysis, guarantee the integrity of the vessel wall and provide effective hemostasis in case of vascular damage. The equilibrium between anticoagulant and procoagulant forces which is essential for the maintenance of the fluidity of blood is controlled by inhibitors, the fibrinolytic system, and the clearance of activated components by the reticuloendothelial system. The proper function of this humoral balance is essentially dependent on hemodynamic factors such as adequate circulation and capillary perfusion.
    Klinische Wochenschrift 02/1986; 64 Suppl 7:14-7.
  • W Kirschstein, D L Heene
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    ABSTRACT: To evaluate the availability of the fibrinolytic system in patients suffering from acute respiratory distress syndrome, ARDS, induced by septicemia or trauma, the following parameters were analysed: fibrinogen, FG, antithrombin III, AT III, plasma prekallikrein, PPK, plasminogen, PG, alpha 2-antiplasmin, alpha 2-AP, alpha 2-macroglobulin, alpha 2-MG, urokinase-inhibitor, UK-I, streptokinase-inhibitor, SK-I, C1-inhibitor, C1-I, alpha 1-antitrypsin, alpha 1-AT, and fibrinogen-fibrin degradation products, FDP. Survivors and non-survivors of septicemia induced ARDS showed a characteristic feature: marked increase of FG and pronounced decrease of AT III and PPK in the coagulation system; concerning the fibrinolytic system a decrease of PG, alpha 2-AP and alpha 2-MG as well as an increase of inhibitors of PG-activators (PG-antiactivators) UK-I, SK-I, C1-I and alpha 1-AT; the FDP-titer was elevated. This constellation of parameters is interpreted as indicative of a marked procoagulant stimulation rendering the organism a state of hypercoagulability coinciding with a diminished availability of the fibrinolytic system, due to exhaustion of the fibrinolytic potential and increase of PG-antiactivators. In the trauma group initially the rise of FG, SK-I, C1-I and alpha 1-AT is absent independent of the outcome, but develops with progression of the disease. As ARDS is more frequently associated with septicemia, diminished availability of the fibrinolytic system simultaneously with increased procoagulant stimulation may be a particular pathophysiologic mechanism in the pathogenesis of ARDS.
    Scandinavian journal of clinical and laboratory investigation. Supplementum 02/1985; 178:87-94.