US experience with recombinant factor VIIa for surgery and other invasive procedures in acquired haemophilia: analysis from the Hemostasis and Thrombosis Research Society Registry.

INTRODUCTION: Acquired haemophilia (AH) is a rare disorder caused by autoantibodies against factor VIII. AIM: The Hemostasis & Thrombosis Research Society (HTRS) Registry was used to monitor the safety of recombinant FVII (rFVIIa). This study aims to report data from the HTRS Registry regarding safety and efficacy of rFVIIa for haemostatic management of surgeries and other invasive procedures in patients with AH. METHODS: For each rFVIIa-treated procedure, the initial dose, total dose, average infused dose, number of doses and treatment duration were calculated. Efficacy was assessed on a 4-point scale. RESULTS: Of 166 registered patients with AH, 37 patients underwent 58 procedures [30 (51%) rFVIIa-treated]. The median (range) age of all patients undergoing procedures was 70 (13-93) years; for rFVIIa-treated patients, 74 (28-89) years. Approximately 67% (39/58) of all procedures were elective. Overall, the most common procedures were endoscopy (12) and central venous access device (10); rFVIIa was used preoperatively (11), postoperatively (13) and during six follow-up procedures during ongoing postoperative rFVIIa treatment. The median (range) initial dose was 90.0 (44-187) µg kg(-1) preoperatively and 106.0 (56-270) µg kg(-1) postoperatively. For rFVIIa-treated episodes with a reported outcome, 20 (91%) were rated excellent/good or no additional agents used and 2 (9%) were rated as poor/ineffective requiring a switch to another bypassing agent. No thromboembolic events were reported. CONCLUSIONS: Adequate haemostasis was provided for 91% of rFVIIa-treated procedures at doses largely conforming to the package insert. No safety concerns were reported.

Human fibroblast adhesion to fibrinogen.

Fibrinogen and fibrin mediate the adhesion of many cell types. In this report, the adhesion sites for human dermal fibroblasts on fibrinogen are identified and characterized. Fibroblasts showed a time- and dose-dependent adhesion to fibrinogen. Using a combination of synthetic peptide mimetics, monoclonal antibodies, and recombinant fibrinogens, two major classes of adhesive sites were identified. One class was RGD-dependent and involved the RGD sites in the alpha chain of fibrinogen. alpha V integrins present on fibroblasts appeared to mediate this adhesion. Inhibition studies showed that the RGD-independent site was blocked by an ICAM-1 antagonist peptide. Furthermore, the inhibition was additive with RGD peptide inhibition and accounted for essentially all of the fibroblast adhesion. Together, these results suggest that fibroblast adhesion to fibrinogen is mediated by both alpha V integrins and ICAM-1.

The effects of latamoxef, cefotaxime, and cefoperazone on platelet function and coagulation in normal volunteers.

A bleeding diathesis characterized by in-vitro platelet dysfunction and prolongation of the template bleeding time (TBT) has been reported in patients receiving latamoxef ('moxalactam'), but not cefotaxime or cefoperazone. Hypoprothrombinaemia has been associated with the use of both latamoxef and cefoperazone in seriously ill and malnourished patients. We administered either latamoxef, cefotaxime or cefoperazone intravenously, at dosages within the range recommended by each manufacturer, to 14 normal volunteers. Latamoxef caused a dose and time dependent defect in platelet function characterized in vitro by abnormalities in aggregation to adenosine diphosphate and in vivo by prolongation of the template bleeding time. In two out of two subjects, a single 4 g dose of latamoxef caused neither prolongation of template bleeding times nor aggregation abnormalities. Two out of two subjects receiving latamoxef 6 g/day for six days had progressive prolongation of bleeding times to 12 and 15 min. Two additional subjects receiving latamoxef 12 g/day for four days had prolongation of template bleeding times to greater than 20 min. Of four subjects receiving cefotaxime 12 g/day for seven days, none had prolongation of template bleeding times or abnormalities in platelet aggregations. Of four subjects receiving cefoperazone 6 g/day, none had significant prolongation of template bleeding times and one had abnormalities in aggregation attributed to inadvertent salicylate ingestion. Prolongation of the prothrombin time or activated partial thromboplastin time did not occur in any of the 14 volunteers. Latamoxef is more likely to interfere with platelet function than either cefotaxime or cefoperazone.

The effect of prostaglandin modulators on prostate tumor growth and metastasis.

The purpose of this study was to investigate the effect of prostaglandin modulating drugs on the growth and metastasis of experimental prostate tumor. Nb rats bearing subcutaneous implants of an androgen-insensitive prostate adenocarcinoma were treated with indomethacin, a cyclooxygenase inhibitor, UK 38485, a thromboxane synthetase inhibitor, and nafazatrom, an antithrombotic agent which is thought to act by enhancing endogenous prostacyclin synthesis. Animals treated with these three drugs had significantly lower pulmonary metastasis than the untreated controls. The effect on primary tumor volume and mortality was variable. We conclude that shifting prostaglandin hemostasis in the tumor bearing animals in favor of prostacyclin, reduces pulmonary metastasis in this experimental tumor system.

Carcinoma of the pancreas in Iraq.

This paper presents clinical observations on 130 patients with carcinoma of the pancreas, including 19 with periampullary cancer, the first large study of this disease in Iraq. All of the patients were admitted to the First (one of three) Surgical Unit of the University of Baghdad Teaching Hospital (the Medical City) during the period 1965-1977. The diagnosis and extent of disease were confirmed surgically in all patients. The clinical presentation, histopathologic characteristics, and prognostic features of the disease in Iraq seem no different from those seen in other parts of the world. Though relatively uncommon (1.4% of all male and 1.2% of all female cancers in the Baghdad Cancer Registry), cancer of the pancreas is the second most common tumor of the digestive system, next to that of the stomach.

Aplastic anaemia in Iraq. A prospective study.

The problem of aplastic anaemia (AA) in Iraq has not been previously investigated. This paper describes 60 patients evaluated prospectively at the University of Baghdad Teaching Hospital during the period 1975--1978. Criteria for the diagnosis included pancytopenia and hypocellular or acellular bone marrow. A surprising finding at variance with published reports about the disease from other parts of the world was a 3 : 1 preponderance of males over females. A discernible aetiology of drug or chemical exposure was detected in half of the patients. Chloramphenicol, alone or in combination with other antibiotics, was thought to be responsible for marrow injury in 12 patients. The occurrence of AA seems to be on the rise in Iraq, probably as a result of the increased use of potentially toxic therapeutic agents and chemicals, and of the growing environmental pollution.

Inherited bleeding syndromes in Iraq.

This paper presents data on the occurence and pattern of inherited bleeding syndromes (IBS) in Iraq, a hitherto unexplored problem. During the first fourteen months of a prospective on-going study at a major university center, 116 patients from 62 families were diagnosed as having IBS. All patients were referred because of moderate to severe bleeding diatheses. They included 62 haemophiliacs 32 patients with von Willebrand's disease (VWD), 9 with Christmas disease (CD), 6 with afibrinogenemia, 1 with prothrombin deficiency, and 6 were thought to have platelet dysfunction. 32 other bleeders (16 hemophiliacs, 14 VWD, and 2 CD) were also recognized among the pedigrees studied but were not available for full investigations. The clinical and laboratory features of the patients observed in Iraq do not seem to be significantly different from those of patients in Western Europe or North America. Although the absolute incidence and relative distribution of these disorders in the entire population cannot yet be determined, the rate of occurence per segment population is likely to be high, most likely due to the high rate of consanguinity and large number of births per family, phenomena still prevalent in this country.