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ZusammenfassungVor allen operativen oder anderen invasiven Eingriffen, die mit gefährlichen Blutungen einhergehen können, muss eine hämorrhagische Diathese anamnestisch, ggf. anhand der klinischen Symptomatik und laboranalytisch ausgeschlossen werden. Auf keine dieser Maßnahmen kann verzichtet werden. Die Blutungsanamnese wird mit einem standardisierten Fragebogen unter Verwendung eines Scores und unter ärztlicher Anleitung erhoben. Falsch positive und falsch negative Blutungsanamnesen kommen häufig vor. Das laboranalytische Minimalprogramm besteht aus Thrombozytenzahl, aktivierter partieller Thrombo plastinzeit (aPTT) und Quick-Wert in % der Norm. Eine Ergänzung durch die Bestimmung des Fibrinogens ist sinnvoll. Ein zuverlässiges Screening für häufige Thrombozytopathien und das von-Willebrand-Syndrom steht nicht zur Verfügung. Ergeben Anamnese oder Symptomatik oder Labor-Screening den Verdacht auf eine hämorrhagische Diathese, muss eine präoperative Abklärung in einem hämo staseologischen Labor erfolgen.

A randomized and controlled study was undertaken to test whether substitution with factor XIII concentrates influences the clinical course in patients with acute leukaemia and acquired factor XIII deficiency (less than or equal to 60%). A control group of 31 patients was compared with a factor XIII-treated group of 29 patients. Partial factor XIII deficiency was successfully corrected by substitution. On the other hand, there was no statistically significant difference between the two patient groups in the frequency and severity of bleeding complications, transfusion requirements, and the number of remissions. Undesirable side-effects as a result of substitution treatment were not observed.

During postoperative prophylaxis of thrombosis using subcutaneous low-dose heparin thrombocytopenia and consumption coagulopathy without manifest haemorrhage were observed in a female patient with gynaecologic problems on the tenth postoperative day. Using gel-electrophoresis, demonstration of cross-linked fibrin derivatives, which occur only after contact with thrombin, was proof that disseminated intravascular coagulation must have been present. Cancellation of heparin prophylaxis was sufficient for regression of the haemostatic disorder. Platelet function tests performed two months later showed as the only reproducible abnormality that the patient's plasma caused inhibition of desaggregation of normal platelets only when heparin was present. The remarkably close chronologic connection of heparin prophylaxis with thrombocytopenia and consumption coagulopathy suggests a possible causal connection. However, at present the possibly heterogeneous aetiology cannot be explained satisfactorily.

HISTORY An 80-year-old woman had been hospitalized in a psychiatric clinic where, on the 22nd day, she sustained a fracture of the neck of the left femur, which was treated by internal screw fixation. The postoperative course was at first without complication. But 9 days postoperatively her platelet count had fallen to 59,000/microliter. As heparin induced type II thrombocytopenia (HIT II) was suspected, the thrombosis prophylaxis with low-molecular heparin was replaced by sodium danaparoid (twice 750 units subcutaneously). Despite this, ischaemia of the right lower leg developed and required amputation. On the following day the left lower leg and foot also became ischemic, where upon she was admitted to the author's hospital (37 days after her admission to the psychiatric clinic). ADMISSION FINDINGS The patient was in a reduced general condition (body-mass index 19.5 kg/m2). She was disoriented as to place and time. Her blood pressure was 140/80 mmHg, her pulse irregular with a ventricular rate of 100/min. The skin below the middle of the left lower leg was cold and livid and the pedal pulses were not palpable. LABORATORY TESTS Haemoglobin content was 9.7 g/dl, the white cell count 9,200/microliter, and platelet count 54,000/microliter. Electrolytes and creatinine were within normal limits. TREATMENT AND COURSE Thrombendarterectomy was performed once via the left groin under danaparoid anticoagulation. There was no re-occlusion and the patient was able to walk again.--It was ascertained subsequently, she had already been given ordinary heparin in the psychiatric clinic for 20 days. Her platelet count of around 70,000/microliter returned to normal even though heparin administration was continued. CONCLUSION A reduction in platelet count by more than half during heparin treatment suggests heparin-induced thrombocytopenia, in which case heparin should be discontinued at once. In high-risk patients adequate treatment should be initiated with other anticoagulants even before the occurrence of thromboembolism.

The antithrombotic potential of oral anticoagulants is undisputed as the frequency of recurrent thrombosis is high unless anticoagulant therapy is continued after hospital discharge. However, the relationship between potency and/or changes in anticoagulant therapy and frequency of complications remains unclear. Optimizing the clinical management of oral anticoagulation information obtained by databases may be advantageous in addition to meeting safety criteria, as described in the "Saarland Model." The Phoenix-database implicates an association between bleeding complications and the hypertensive elderly. From 1968 to 1993 most reports about cerebral/intraspinal bleedings occurred at prothrombin (PT)-values below 20% in the elder patients (>60 years of age) (12%; 367 reports). In the Saarland Model, 60 patients were followed from our department during a 3-year period. Our findings suggest neither a correlation of the range of PT values and the bleeding events nor an association with age or hypertension. It became obvious that "stable phases" of International Normalized Ratio (INR) [+/-15% change of 4 serial controls using nearly constant weekly oral anticoagulant dosages (+/-15%)] might be considered as a valid criterion of safety. At least the individual risk profile determines the patient's fate.

SummaryInitially, hydroxyethyl starch (HES) was only characterized by its in vitro molecular weight (MW). This is not sufficient because HES is degraded in vivo. One relevant parameter that predicts the rate of enzymatic breakdown is the degree of substitution, a measure of the average number of hydroxyethyl groups per glucose unit. The higher this degree of substitution, the slower the break-down. In addition, because the glucose units can be substituted at carbon 2,3 and 6, different substitution patterns are possible. They are classified by their C2/C6 hydroxyethylation ratio. A higher C2/C6 ratio results in less metabolism of the starch in vivo and results in a larger in vivo MW. This in turn affects therapy, because the larger the in vivo MW, the longer is the duration of the volume effect of HES.Of particular importance is the fact that HES with a high in vivo MW affects factor VIII/von Willebrand factor which can lead to an acquired von Willebrand syndrome. During a 10-day volume therapy with a medium-MW HES 200, a form that is difficult to metabolize, we observed an 80% drop in factor VIII/von Willebrand factor. Therapy with a medium-MW HES 200, a form that is easily degraded, and therapy with a low-MW HES 70 did not result in a relevant decline of factor VIII/von Willebrand factor.This explains why hemorrhagic complications have been observed repeatedly in the United States after therapy with HES infusions, some of them lethal. In the United States high-MW HES 480 which is difficult to degrade is most frequently used and results in a larger in vivo MW and subsequent decrease in factor VIII/von Willebrand factor levels. In Europe, medium-MW HES 200 that is easily degraded and low-MW HES 70 are preferred. In the future, HES should be characterized by the in vivo, not the in vitro MW.

ZusammenfassungIn klinischen Studien ist die Wirksamkeit der Prophylaxe mit Heparin zur Verhütung von Venenthrombosen und Lungenembolien im Verlauf der letzten 20 Jahre statistisch überzeugend gesichert worden. Die Ergebnisse klinischer Studien dürfen allerdings nicht als Endresultat klinischer Forschung angesehen werden. Die Resultate einer randomisierten klinischen Studie lassen zunächst im Sinne eines Basiswertes die Nutzen-Risiko-Relation eines Medikamentes erkennen. In klinischen Studien werden spezielle Patientenkollektive geprüft, die Ergebnisse lassen sich daher häufig nicht unmittelbar in Indikation und Kontraindikation auf einen individuellen Patienten übertragen. Für den praktizierenden Kliniker ist es notwendig, diese Entscheidungshilfen der zugängigen Standardliteratur zu entnehmen. Es wird dargelegt, wie wenig informativ Indikationen und Kontraindikationen zur Heparinprophylaxe in Fachinformationen und Roter Liste, speziell unter dem Gesichtspunkt der Risikosituation des Patienten, dargelegt werden. Konsensus-Konferenzen und Empfehlungen von ärztlichen Experten sind notwendig, um in der Praxis die Resultate klinischer Studien auf individuelle Patienten und Risiko-Nutzen-Überlegungen zu übertragen. Endziel ist es, die Ergebnisse klinischer Studien bei der antithrombotischen Therapie so umzusetzen, daß die Sicherheit erhöht wird, ohne daß die Wirksamkeit vermindert wird.

SummaryThe plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch.10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7.After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (pThe higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.