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Wir berichten uber einen schweren Morbus haemolyticus neonatalis eines rhesusnegativen Kindes (Ccddee). Das Neugeborene wurde 2 Tage nach zeitgerechter vaginaler Entbindung der Mutter (G2, P2; Rhesusformel ccddee) notfallmasig aus einem peripheren Haus in das Universitatsklinikum Dusseldorf verlegt. Bei Ubernahme bot das Kind einen Icterus gravis (Ges.-Bilirubin > 30 mg/dl) bei Hamolyse (LDH > 1500 U/l), aber noch normwertigem Hamoglobin (13,7 g/dl). Unter Austauschtransfusion mit dem 3-fachen kindlichen Blutvolumen fiel das Ges.-Bilirubin auf 18 mg/dl, bei weitergefuhrter intensiver Phototherapie innerhalb von 24 h auf 12 mg/dl. Nach erfolgreicher Behandlung einer bereits bei Aufnahme bestehenden Sepsis konnte das Kind in gutem Allgemeinzustand entlassen werden. Ursache des Morbus haemolyticus neonatalis war eine erst postpartal diagnostizierte Alloimmunisierung durch antierythrozytare Antikorper der Spezifitaten Anti-C und Anti-G in Kombination. Zwar wurde bei der Mutter auswarts ein als Anti-D fehlinterpretierter Alloantikorper ab der 8. SSW mit steigendem Titer gefunden, aber keine erneute Rhesusprophylaxe durchgefuhrt. Diese Entscheidung stutzte sich offenbar auf den molekulargenetischen Befund „keine fetalen D-spezifischen Nukleinsaurepolymorphismen“ und fehlende indirekte Hinweise einer fetalen Hamolyse im weiteren Schwangerschaftsverlauf. Unsere immunhamatologischen Untersuchungen ergaben, dass die Mutter vermutlich bereits in ihrer Erstschwangerschaft (Rhesusformel von P1 Ccddee) immunisiert worden war und nun einen weiteren irregularen Antikorper der Spezifitat Anti-G entwickelt hatte. Die Besonderheit des G-Antigens liegt darin, dass es auf Erythrozyten exprimiert wird, welche das C- und/oder D-Antigen tragen. Durch diese Assoziation kann ein Anti-G-Antikorper wie eine Kombination aus Anti-C und Anti-D erscheinen und verkannt werden. Bei dem Reaktionsmuster „Anti-C und Anti-D“ sind unterschiedliche Kombinationen von Anti-C, Anti-D und Anti-G in Betracht zu ziehen. Die genaue Differenzierung der Antikorperspezifitaten erfolgt durch Absorptions- und Elutionsuntersuchungen mit spezifischen Testerythrozyten. Bei Ausschluss eines Antikorpers der Spezifitat Anti-D ist bei rhesusnegativen Schwangeren mit einem rhesuspositiven Feten unbedingt eine Rhesusprophylaxe indiziert.

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.

An open, prospective study was performed to evaluate the clinical usefulness of sodium chloride loading for prevention of amphotericin-B-induced nephrotoxicity in 37 patients requiring 44 courses of amphotericin B treatment. The median duration of the treatment course was 22 days (range, 9-136 days), and mean cumulative dose per patient was 1117 mg (range, 231-7831 mg). During amphotericin B treatment, all patients received 50 to 100 ml of 10% sodium chloride (85 to 171 mmol NaCl) via an intravenous line for prevention of amphotericin-B-induced nephrotoxicity evaluated by serum creatinine levels. Using this regimen, none of the patients developed significant nephrotoxicity (increase in serum creatinine of more than twice baseline level, or serum creatinine level greater than or equal to 2.0 mg/dl, respectively) despite the co-administration of other potentially nephrotoxic drugs. It was not necessary to discontinue treatment with amphotericin B in any of the patients. There were no side effects due to sodium chloride loading. Our results demonstrate that sodium chloride loading is useful for the prevention of amphotericin-B-induced nephrotoxicity.

The etiology of cerebrovascular disease (CDV) in young patients is difficult to establish if the common causes of a focal neurological deficit are excluded by appropriate investigations. Since in some observations prolapse of the mitral-valve (MVP), alterations of platelet function, or both have been linked with cerebral ischemic events, we studied the in vivo platelet release reaction and the incidence of MVP in 47 patients (12 males, 35 females) under 45 years of age with TIA or stroke of unknown cause and in an age- and sex-matched control group. The mean plasma beta-thromboglobulin (beta-TG) level of the patients (mean = 54.9 +/- 31.4 ng/ml) was significantly higher than that of the controls (mean = 20.6 /- 6.9 ng/ml, p less than 0.001). MVP was demonstrated in 13 of 47 patients in contrast to 4 of the controls (p less than 0.01). However, the beta-T levels of patients with MVP (n = 13, 52.9 +/- 25.5 ng/ml) did not differ from those of patients without MVP (n = 34, 55.7 +/- 33.7 ng/ml) significantly (p less than 0.4). Our results confirm that the incidence of MVP is higher in young patients with cerebral ischemia of unknown cause than in asymptomatic controls. The significantly elevated plasma beta-TG concentrations in the patient's group indicate an increased platelet activity in vivo. Since there was no significant difference between beta-TG levels of patients with and without MVP, the mitral-valve abnormality can not be the cause for the altered platelet activity.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder which usually occurs in young adults. It is characterized by a pentad of clinical findings: fever, neurological abnormalities, renal dysfunction, microangiopathic hemolytic anemia and thrombocytopenia. The histological hallmark is the presence of platelet thrombi occluding the microcirculation of multiple organs. The etiology and pathogenesis of disseminated platelet aggregation are uncertain and obviously not uniform in individual patients. Experimental findings suggest that microthrombi may result from intravascular platelet activation or form secondarily at sites of vessel wall damage. The differential diagnosis of TTP includes the hemolytic uremic syndrome in which the microangiopathic changes are exclusively found in the kidneys. When untreated, TTP invariably runs a progressive and fatal course. In recent years, prognosis has been improved by new forms of therapy such as plasmapheresis or infusions of fresh frozen plasma which may lead to recovery in about 80% of patients.

Besides decreased platelet production and an increased platelet sequestration in the spleen chronic DIC is thought to cause thrombocytopenia in chronic liver diseases. To investigate if this mechanism could play a role in patients with severe, but stable hepatic cirrhosis, we studied 32 pts. Twenty-eight of them had portal hypertension, 22 had bleeding episodes from oesophageal varices.

The role of variations in plasma insulin concentrations as a factor possibly involved in abnormalities of haemostatic functions, and (or) the development of arterial disease, has been the subject of controversy. This study examines the "in vivo" effect of hyperinsulinaemia on haemostatic parameters in seven healthy men. Two studies were carried out in random order: (a) Hyperinsulinaemia study. Human insulin was infused by a calibrated infusion pump (0.7 mU kg-1 min-1, for 8 h) during a euglycaemic glucose clamp, and (b) Control study 0.15 mmol/l NaCl solution was infused over 8 h. Plasma epinephrine and norepinephrine concentrations remained constant throughout the studies. Mean insulin levels during the hyperinsulinaemia study were 46.2 +/- 1.6 microU/ml, i.e. approximately eightfold higher than those at baseline, whereas plasma glucose levels remained constant at 4.9 +/- 0.1 mmol/l. During the control study, mean insulinaemia was 5.0 +/- 0.9 microU/ml, and plasma glucose 5.2 +/- 0.1 mmol/l. No statistically significant changes were observed during, or after insulin or 0.15 mmol/l NaCl infusions with regard to platelet parameters, blood coagulation, and coagulation inhibitors. These data suggest that abnormalities of the haemostatic function described during insulin-induced hypoglycaemia or in hyperinsulinaemic patients are not due to a direct action of insulin.