Background information about the variation in the risk for venous thromboembolism (VTE) and in prophylaxis practices around the world is scarce. The ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study is a multinational cross-sectional survey designed to assess the prevalence of VTE risk in the acute hospital care setting, and to determine the proportion of at-risk patients who receive effective prophylaxis.Methods All hospital inpatients aged 40 years or over admitted to a medical ward, or those aged 18 years or over admitted to a surgical ward, in 358 hospitals across 32 countries were assessed for risk of VTE on the basis of hospital chart review. The 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines were used to assess VTE risk and to determine whether patients were receiving recommended prophylaxis.Findings 68183 patients were enrolled; 30 827 (45%) were categorised as surgical, and 37 356 (55%) as medical. On the basis of ACCP criteria, 35 329 (51.8%; 95% CI 51.4-52.2; between-country range 35.6-72.6) patients were judged to be at risk for VTE, including 19 842 (64.4%; 63.8-64.9; 44.1-80.2) surgical patients and 15 487 (41. 5%; 41.0-42. 0; 21.1-71.2) medical patients. Of the surgical patients at risk, 11613 (58.5%; 57.8-59.2; 0.2-92.1) received ACCP-recommended VTE prophylaxis, compared with 6119 (39.5%; 38.7-40.3; 3.1-70.4) at-risk medical patients.Interpretation A large proportion of hospitalised patients are at risk for VTE, but there is a low rate of appropriate prophylaxis. Our data reinforce the rationale for the use of hospital-wide strategies to assess patients' VTE risk and to implement measures that ensure that at-risk patients receive appropriate prophylaxis.

SummaryLimited data are available regarding the risk for venous thromboembolism (VTE) and VTE prophylaxis use in hospitalised medically ill patients. We analysed data from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this population according to diagnosis, baseline characteristics, and country. Data on patient characteristics, VTE risk, and prophylaxis use were abstracted from hospital charts. VTE risk and prophylaxis use were evaluated according to the 2004 American College of Chest Physicians (ACCP) guidelines. Multivariable analysis was performed to identify factors associated with use of ACCP-recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical patients across 32 countries. VTE risk varied according to medical diagnosis, from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of patients with acute heart failure, active non-infectious respiratory disease, or pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP-recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40–45% of cardiopulmonary disease patients (global rate, 39.5%). Large differences in prophylaxis use were observed among countries. Markers of disease severity, including central venous catheters, mechanical ventilation, and admission to intensive care units, were strongly associated with use of ACCP-recommended prophylaxis. In conclusion, VTE risk varies according to medical diagnosis. Less than 40% of at-risk hospitalised medical patients receive ACCP-recommended prophylaxis. Prophylaxis use appears to be associated with disease severity rather than medical diagnosis. These data support the necessity to improve implementation of available guidelines for evaluating VTE risk and providing prophylaxis to hospitalised medical patients.

1 Treatment of patients with FXIII de®ciency with prophylactic infusion of Fibrogamin-P: patient education and follow-up D. BASHARI,* R. POWSNER,* N. CASPI,* U. MARTINOWITZ* and A. INBAL The National Hemophilia Center; and the Institute of Thrombosis Hemostasis, Sheba Medical Center, Tel-Hashomer 52621, Israel FXIII is the last factor of the coagulation cascade. It stabilizes the ®brin clot by crosslinking the amino acid lysine-glutamyl, thereby producing the ®nal ®rm clot. Hereditary FXIII de®ciency is a rare disease. Homozygous patients suffer from severe lifelong bleeding episodes, delay in wound repair and recurrent abortions in females. Because of severe life-threatening bleeding, prophylaxis with FXIII concentrate (Fibrogamin-P) is recommended. Due to its long half-life (~10 days) this concentrate can be administered every 3±4 weeks. Six families with hereditary F XIII de®ciency have been diagnosed at our Institute of Thrombosis and Hemostasis, ®ve of whom are under our follow-up for over 7 years. In four out of the six families the mutation that causes F XIII de®ciency was identi®ed: leucine by proline substitution at amino acid 660 (Leu 660 Pro). The affected members from the ®ve families have been educated to self-inject Fibrogamin-P, 10 U kg intravenously. Since then the patients have been treated constantly by 3±4 weekly infusions of Fibrogamin-P. Over the 3 years of follow-up while on prophylactic treatment none of the treated patients experienced bleeding. In addition, in one of the patients, who underwent left hemicolectomy with transverse colostomy due to colon carcinoma while receiving Fibrogamin, no bleeding was observed. Patients' education with regard to the nature of the disease and importance of prophylactic treatment contributed signi®cantly to their understanding of the genetics of FXIII de®ciency and the appropriate prevention of bleeding or other complications.

. Factor VII (FVII) deficiency is a rare haemorrhagic condition, normally inherited as an autosomal recessive trait, in which clinical presentation is highly variable and correlates poorly with laboratory phenotype. The FVII ( F7 ) gene was sequenced in 48 unrelated individuals with FVII deficiency, yielding a total of 23 novel lesions including 15 missense mutations, 2 micro-deletions, 5 splice junction mutations and a single base-pair substitution in the 5' untranslated region. Family studies were performed in order to distinguish the contributions of individual mutant F7 alleles to the clinical and laboratory phenotypes. Specific missense mutations were evaluated by molecular modelling in the context of the FVIIa-tissue factor crystal structure. Single base-pair substitutions in splice sites and the 5' untranslated region were studied by in vitro splicing assay and luciferase reporter gene assay, respectively. All probands were also typed for four previously reported F7 polymorphisms. In the majority of cases of FVII deficiency studied here, consideration of both mutational and polymorphism data permitted the derivation of plausible explanations for the FVII activity and antigen levels measured in the laboratory. Inter-familial variation in FVII activity and the antigen levels of heterozygous relatives of probands was found to be significantly higher than intra-familial variation, consistent with the view that the nature of the F7 gene lesion(s) segregating in a given family is a prime determinant of laboratory phenotype. Although no relationship could be discerned between laboratory phenotype and polymorphism genotype, the frequencies of the A2 and M2 polymorphic alleles were significantly higher in the FVII-deficient individuals tested than in controls. This suggests that the presence of these alleles may have served to increase the likelihood of pathological F7 gene lesions coming to clinical attention.

Two unrelated female infants with homozygous protein C (Pr C) deficiency are reported. Both are of U.K. Pakistani origin and in each case the parents are consanguinous. A previous sibling had died in each family. Both sets of parents were shown to be carriers. The concentration of Pr C in both infants was low at birth. Both developed necrotic skin lesions (purpura fulminans) and responded well to Pr C concentrate. Both are developing normally although one has visual impairment due to retinal artery thrombosis which occurred before treatment was commenced. Both infants are treated with intravenous Pr C concentrate administerd daily by the parents at home. Studies of the half-life of exogenous Pr C in one of the patients has shown an increase from 2.7 to 10.8 h during the course of treatment thus enabling it to be administered once daily while still maintaining effective plasma concentrations. In the other patient half-life has fluctuated but Pr C is also given once daily. This is the first report of this condition being treated in this way in the United Kingdom.

Twenty-five patients with either previously untreated advanced Hodgkin's disease (HD) or with relapsed disease were treated with an intensive weekly chemotherapy regimen (ChlOPhEPP-B) in which the myelo-suppressive combinations of epirubicin and chlorambucil, and procarbazine and etoposide alternated at two-week intervals, interspersed with vincristine and prednisolone and then vincristine, prednisolone and bleomycin. in a four-week cycle. Of the previously untreated patients (n = 14), 12 (86 per cent) showed a complete response (CR); in the previously treated patients (n = 11), CR was achieved in five (46 per cent). Toxicity was predictable and not evidently more severe than with more standard regimens. Neutropenia leading to treatment delay and/or dose reduction was seen in 11 patients (44 per cent) but severe neutropenia (WHO grade 4) was documented in only six patients (24 per cent) for a cumulative total of nine treatment weeks (1.8 per cent of the total treatment time). Dose reductions for neutropenia were applied in relation to 11 of the 379 weekly treatment points (2.9 percent). Delays in treatment, for any reason, averaged 3.65 weeks per patient. The study demonstrated the feasibility of a more intensive weekly multidrug schedule. This approach may be applicable in the treatment of advanced HD and represents a further option in the strategy of treating relapsed disease.

Fifty-seven patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 33 patients with NHL evaluable for response, 10 (30 per cent) achieved complete remission and six partial remission, giving an overall response rate of 48 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 18 patients with HD evaluable for response, seven (39 per cent) achieved complete remission and six partial remission, giving an overall response rate of 72 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. The possibility of increasing the safety of the regimen by increasing the time of infusion to 72 h is discussed. Given the need to offer alternative treatment to patients in these categories, this combination (I-M) is of value in relapsed patients, especially where options are limited because of previous multi-drug treatment. Remissions may not be prolonged but allow the effective application of additional intensive treatment including bone marrow transplantation.

Fifty‐five patients, initially diagnosed as having advanced high grade non‐Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first‐line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three‐weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)—one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I‐M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi‐drug treatment.

Monoclate is a new generation of Factor VIII concentrate produced by purification using mouse monoclonal anti-Factor VIII:R antibody. As the- Factor VIII:C does not interact with the antibody it can be eluted by disrupting the Factor VIII:C - Factor VIII:R complex using a high concentration of calcium ions. The eluted Factor VIII:C is concentrated and purified. The method of manufacture has demonstrated efficacy in the elimination of infectious viral particles. The first “virgin” haemophiliac to be treated by this has completed 20 weeks follow-up. The patient, a child of 18 months with a Factor VIII:C level of 2.8%, was treated with 190 × 4 units of the Factor VIII concentrate for a severe cut of the lower lip. The HIV status has remained negative. The AST and ALT enzymes have remained within normal limits. Other parameters which have remained normal are Gamma GT, WBC and lymphocyte counts, T cell subsets and B cell ratios. The patient has remained well and no side effects have been noted. Mouse antibody titres are being carried out and the results will be presented at the conference.

Twenty-five patients with immunologically classified B cell chronic lymphocytic leukaemia (CLL) were examined for skin lesions. Six showed evidence of cutaneous involvement, and histological examination of skin biopsies from these patients revealed perivascular lymphocytic infiltration with some diffuse involvement in three. Immunohistological analysis with a range of B and T cell specific monoclonal antibodies revealed that in all cases the infiltrate was predominantly T cell in origin and that epidermotropism in three cases was also associated with T cell components. Six control patients with macroscopically normal skin were also biopsied and these biopsies subjected to the same assessment. All were normal.

37 lighting can be experimented with to achieve the optimum modelling effect. The results obtained are accurate and reproducible. This technique has been used for photomicroscopy of normal skin features and abnormalities of the skin. Skin diseases that have been studied include Gorlin's syndrome, graft-versus-host disease, disseminated superficial actinic porokeratosis, Anderson-Fabry disease and acne vulgaris. Some examples will be demonstrated.

Cytotoxic agents and aminoglycosides when given for a maximum of eleven days damaged the renal tubules as indicated by an increased urinary beta 2-microglobulin (beta 2-m), N-acetyl-beta-D-glucosaminidase (NAG) and total protein. Methotrexate (MTX) caused the greatest changes among the cytotoxic agents studied. Prophylactic doses of aminoglycosides in surgical patients also caused tubuloproteinuria. The tubular damage was greatest when aminoglycosides were given to treat septicaemia complicating haematological malignancies in patients who had previously had cytotoxic drugs. However, even in these patients there was no evidence of glomerular failure or increased glomerular permeability seven days after beginning chemotherapy.

The serum and urinary concentrations of beta 2-microglobulin (beta 2-m) and creatinine and the urinary concentration of albumin and IgG were measured in 14 patients with hematologic malignancies before and during chemotherapy. There was a transient increase in urinary beta 2-m in nine of the 14 patients during chemotherapy. All of the nine patients but only one of the other five patients had had recent multiple chemotherapy. The urinary beta 2-m increased in 24 courses of chemotherapy given to these nine patients and was already abnormal before 13 of these courses. The increase in urinary beta 2-m was not associated with an increase in serum beta 2-m or a significant increase in urinary albumin or IgG excretion. These results suggest that chemotherapy causes a marked transient tubular proteinuria, particularly in patients who have had previous chemotherapy.