[Pitfall in coagulation tests]. / Pitfalls bei Gerinnungsuntersuchungen.

Coagulation assays are prone to pre-analytical problems and results may be influenced by varying clinical and pharmaceutical aspects. Particularly anticoagulants interact with coagulation testing in many ways. Thromboplastin time will be prolonged dose-dependently in patients taking vitamin K antagonists; moreover the new oral anticoagulants have been shown to have variable impact on the results of the thromboplastin time as well as on other coagulation tests, depending on the mechanism of action of these new drugs as well as on the mechanism of the coagulation test. When measuring anti-Xa activity it should be realised that all drugs with anti-Xa activity will influence the result, which means not only heparins but also the new anti-Xa inhibitors. Respective calibration curves are an indispensable condition to provide the clinician with valuable results. On the other hand this implies that the laboratory knows which anticoagulant is given to the patient. This is an example among others that clinical aspects are important to know for proper interpretation of the results of coagulation testing. Other examples are e. g. bleeding disorders, actual bleeding status or thromboembolic events. Several cases are discussed which exemplify possible pitfalls in the interpretation of coagulation testing.

Intravascular lymphoma mimicking cerebral stroke: report of two cases.

Ischemic stroke is a serious disease leading to significant morbidity and mortality. Multifocal and recurrent strokes are usually caused by embolic diseases, i.e. atrial fibrillation, but rare causes like cerebral vasculitis and clotting disorders are also well known. Here we report on two patients suffering from the very rare intravascular large B-cell lymphoma leading to multifocal and recurrent strokes in the brain and spinal cord as the prominent neurological symptom. The difficulties and the need for diagnostic brain biopsy in making an 'in vivo' diagnosis in this particular disease are outlined. Furthermore, the prerequisite for an interdisciplinary approach in these patients is strongly emphasized. Delayed diagnosis for several reasons was the most probable cause for cerebral relapse leading to death in one patient a few months after diagnosis. Conversely, early initiation of immunochemotherapy with a classical lymphoma schedule (R-CHOP) led to long-lasting remission of the disease in the other patient. With this report we like to improve alertness to intravascular large B-cell lymphoma as a cause for multifocal and recurrent strokes.

[Anemia -- the first step in its differential diagnosis]. / Anämien - die ersten Schritte in der Differentialdiagnose.

Anemia is a common manifestation, and has to be considered more often as a symptom of an underlying, acquired or hereditary disease, rather than a disease by itself. The different causes of anemia cover almost the whole spectrum of human diseases. Often the question arises, if anemia is symptom of an already known disease or if other reasons should be investigated. We will present in this paper general considerations of the assessment of anemia and the differential diagnosis, and focus on a possible initial approach to the patient with anemia.

Factor XIII substitution in surgical cancer patients at high risk for intraoperative bleeding.

BACKGROUND: Excessive intraoperative bleeding is associated with significant morbidity and mortality. The authors and others have shown that fibrin monomer allows preoperative risk stratification for intraoperative blood loss, likely due to an imbalance between available factor XIII and prothrombin conversion. The authors hypothesized that the use of factor XIII would delay the decrease of clot firmness in high-risk patients. METHODS: The concept was tested in a prospective, randomized, double-blind, placebo-controlled trial in elective gastrointestinal cancer surgery. Patients were randomized to receive factor XIII (30 U/kg) or placebo in addition to controlled standard therapy. RESULTS: Twenty-two patients were evaluable for a planned interim analysis. For the primary outcome parameter maximum clot firmness, patients receiving factor XIII showed a nonsignificant 8% decrease, and patients receiving placebo lost 38%, a highly significantly difference between the two groups (P = 0.004). A reduction in the nonprimary outcome parameters fibrinogen consumption (-28%, P = 0.01) and blood loss (-29%, P = 0.041) was also observed in the factor XIII group. Three patients experienced adverse events that seemed unrelated to factor XIII substitution. The trial was stopped early after a planned interim analysis with the primary endpoint reached. CONCLUSIONS: This proof of concept study confirms the hypothesis that patients at high risk for intraoperative blood loss show reduced loss of clot firmness when factor XIII is administered early during surgery. Further clinical trials are needed to assess relevant clinical endpoints such as blood loss, loss of other coagulation factors, and use of blood products.

Preoperative fibrin monomer measurement allows risk stratification for high intraoperative blood loss in elective surgery.

We recently demonstrated that patients with increased blood loss due to intraoperative coagulopathy show a persistent pre-, intra- and postoperative increase in fibrin monomer concentration. We thus tested the hypothesis that preoperative fibrin monomer concentrations can be used as a risk indicator for intraoperative blood loss in a study designed for diagnostic test evaluation in 168 patients admitted to the surgical service of our hospital. Intraoperative blood loss increased with preoperative fibrin monomer concentration (median blood loss of 50, 100, 200 and 400 ml in preoperative fibrin monomer quartile groups 1 to 4, p<0.001, ANOVA on ranks; interquartile comparisons p < 0.05 (4/6), Mann Whitney Rank Sum test). In contrast, intraoperative blood loss was unrelated to preoperative values of prothrombin time, activated partial thromboplastin time and platelet count. By multivariate (logistic regression) analysis, only fibrin monomer remained a significant predictor of intraoperative blood loss > 500 ml when age, gender, BMI, fibrin monomer and the different types of surgical procedures (tumor surgery, vascular surgery, cholecystectomy, gastric banding, varicous vein surgery and hernia repair) were included as independent variables. Most importantly, accuracy evaluation showed that preoperative fibrin monomer concentration < 3 microg/l excluded intraoperative blood loss > 500 ml with 92% sensitivity and 95% negative predictive value. These results support our hypothesis that preoperative fibrin monomer concentrations are related to intraoperative blood loss in elective surgery. Fibrin monomer should be further investigated for it's potential to serve as a routine tool for preoperative risk stratification of intraoperative bleeding.