Long-term cosmetic changes after breast-conserving treatment of patients with stage I-II breast cancer and included in the EORTC 'boost versus no boost' trial.

BACKGROUND: In breast cancer treated with breast-conserving radiotherapy, the influence of the boost dose on cosmetic outcome after long-term follow-up is unknown. PATIENTS AND METHODS: We included 348 patients participating in the EORTC 'boost versus no boost' mega trial with a minimum follow-up of 6 years. Digitalised pictures were analysed using specific software, enabling quantification of seven relative asymmetry features associated with different aspects of fibrosis. RESULTS: After 3 years, we noted a statistically significantly poorer outcome for the boost patients for six features compared with those of the no boost patients. Up to 9 years of follow-up, results continued to worsen in the same magnitude for the both patient groups. We noted the following determinants for poorer outcome: (i) boost treatment, (ii) larger excision volumes, (iii) younger age, (iv) tumours located in the central lower quadrants of the breast and (v) a boost dose administered with photons. CONCLUSIONS: A boost dose worsens the change in breast appearance in the first 3 years. Moreover, the development of fibrosis associated with whole-breast irradiation, as estimated with the relative asymmetry features, is an ongoing process until (at least) 9 years after irradiation.

Hereditary increase of plasma histidine-rich glycoprotein associated with abnormal heparin binding (HRG Eindhoven).

Plasma histidine-rich glycoprotein (HRG) was found to be persistently increased in a patient with a history of recurrent arterial thromboembolic events. The mean concentration was 270% of normal pooled plasma. Increased HRG was found in eight of the 17 relatives studied, but none of them has experienced thrombo-embolism yet. Apparently, increased HRG was hereditary with autosomal dominant inheritance. A significant correlation was found between the increased plasma concentration of the protein and the age of the subjects (P < 0.02), whereas no such relation is present in a normal population. The plasma HRG of the proposita and 9 of her family members displayed abnormal binding to heparin, as assessed in a crossed affinity immuno-electrophoresis system: the usual increase in mobility after binding to heparin was absent. The binding of this variant HRG to plasminogen was normal. This case represents the first abnormal HRG variant reported and it is proposed to designate it: HRG Eindhoven.

Haemostatic effects in vivo after snakebite by the red-necked keelback (Rhabdophis subminiatus).

We describe a patient who developed a severe coagulopathy after being bitten by a red-necked keelback snake (Rhabdophis subminiatus), a species which is generally considered non-venomous. The patient's blood was incoagulable due to complete depletion of fibrinogen. Comprehensive coagulation studies were performed to identify the mechanism(s) by which the snake toxin caused the coagulopathy. It was found to contain a potent prothrombin activator, probably an activator of protein C and possibly also a factor X activating enzyme. The fibrinolysis was secondary to intravascular fibrin formation; there were no indications for a direct fibrinogenolytic activity in the snake toxin. Remarkably, there was virtually no consumption of antithrombin III, despite extensive thrombin formation; this feature appears to be not uncommon after snake bites, but is still unexplained.

Prevention of in vitro fibrinogenolysis during laboratory monitoring of thrombolytic therapy with streptokinase or APSAC.

In the present study, we systematically investigated aprotinin, epsilon-aminocaproic acid (EACA) and tranexamic acid as inhibitors of fibrinogen breakdown and of the generation of fibrinogen degradation products (FgDP). The experimental setting very closely imitated the conditions in practice when collecting blood from patients receiving thrombolytic therapy with streptokinase or APSAC. The minimal concentration of aprotinin required to completely inhibit fibrinogen breakdown and FgDP generation was 200 KIU/ml blood. This was sufficient even at the highest concentrations of streptokinase and APSAC expected to occur in patients (300 U/ml and 46 nM, respectively). However, 200 KIU/ml aprotinin heavily interfered in the determinations of plasminogen and alpha 2-antiplasmin. Relatively low concentrations of EACA (200 mM) and tranexamic acid (35 mM) were sufficient to prevent FgDP generation, but they interfered in the Clauss assay of fibrinogen. A non-interfering concentration of EACA (7 mM) allowed the inhibition of lower concentrations of APSAC (20 nM) and streptokinase. We conclude that at least 200 KIU aprotinin per ml blood is necessary to effectively inhibit in vitro fibrinogenolysis under circumstances likely to be met in clinical practice during thrombolytic therapy.

Systemic effects of anisoylated plasminogen streptokinase activator complex and streptokinase therapy in acute myocardial infarction. Coagulation aspects of the Dutch Invasive Reperfusion Study.

The systemic effects of intravenous anisoylated plasminogen streptokinase activator complex (APSAC; 30U) and intracoronary streptokinase (250,000U) were compared in 54 patients with acute myocardial infarction. In 3 patients, no signs of a systemic lytic state were observed. In all other patients, significant reductions of coagulation and fibrinolytic factors occurred: fibrinogen levels decreased by 86% in the APSAC group and 81% in the streptokinase group; for plasminogen the decreases were 68 and 66%, and for alpha 2-antiplasmin activity greater than 95 and 94%, respectively. Fibrin(ogen) degradation products were increased 68- and 38-fold, respectively. Although there was a trend for the lytic state to be more profound in the APSAC-treated patients, there was no difference between treatment groups with regard to bleeding complications or therapeutic efficacy, the latter being 79 and 73%, respectively, for APSAC and streptokinase. Total fibrinolytic activity, measured as euglobulin clot lysis time, was sustained for longer in the APSAC group, which may explain the low reocclusion rate in this group in comparison with the streptokinase group.