Venous thromboprophylaxis in UK medical inpatients.

We prospectively assessed the implementation of venous thromboembolism (VTE) prophylaxis guidelines and the impact of grand round presentation of the data in changing clinical practice. Two NHS teaching hospitals were studied for 24 months from January 2003. Patients were risk stratified according to the THRIFT (thromboembolic risk factor) consensus group guidelines and compared with the recommendations of the THRIFT and ACCP (American College of Chest Physicians) consensus groups. Six months following presentation of the initial results, a further analysis was made to assess changes in clinical practice. 1128 patients were assessed of whom 1062 satisfied the inclusion criteria for thromboprophylaxis. 89% of all patients were stratified as having high or moderate risk of developing VTE. Of these only 28% were prescribed some form of thromboprophylaxis-4% received the THRIFT-recommended and 22% received the ACCP-recommended thromboprophylaxis. The vast majority (72%) received no thromboprophylaxis at all. Reassessment, following data presentation at grand rounds, showed a significant increase to 31% inpatients receiving THRIFT (P<0.0001) and ACCP (P=0.002) recommended thromboprophylaxis. However,the proportion of patients receiving no form of prophylaxis barely changed (72% to 69%: P=0.59). We found a gross underutilization of thromboprophylaxis in hospitalized medical patients. A simple grand-round presentation of the data and recommended guidelines to clinicians significantly increased the proportion of patients receiving recommended thromboprophylaxis but did not increase the overall proportion of patients receiving it. We therefore conclude that a single presentation of guidelines is not enough to achieve the desired levels. Such presentations may only serve to make DVT (deep venous thromboembolism) aware clinicians prescribe prophylaxis more accurately.

Optimal timing for processing and cryopreservation of umbilical cord haematopoietic stem cells for clinical transplantation.

Some of the factors that may influence the number and quality of cord blood haematopoietic progenitor cells available for transplantation have been investigated including site of collection, delayed processing after collection and cryopreservation protocol. We used the granulocyte-macrophage progenitor (CFU-GM) and erythroid burst-forming unit (BFU-E) assays to quantify progenitors. The capacity of CFU-GM to produce secondary colonies was used as a measure of progenitor cell quality. We found that: (1) there were no significant differences in total nucleated cells (TNC), mononuclear cells (MNC), CFU-GM or BFU-E numbers in paired specimens from the umbilical vein or veins at the base of the placenta. The potential of the CFU-GM to produce secondary colonies from the two sites was similar; (2) storing cord blood at room temperature or at 4 degrees C resulted in a significant reduction in progenitor cell numbers beyond 9 h; and (3) cryopreservation following either controlled rate freezing or passive cooling reduced MNC numbers, viability and CFU-GM survival insignificantly but the potential of CFU-GM to produce secondary colonies was significantly reduced post cryopreservation (P = 0.04). We conclude that the yield of CB progenitor cells is not affected by the site of collection, but is adversely affected by delays between collection and cryopreservation. Furthermore, cryopreservation reduced the CFU-GM potential to produce secondary colonies. Measures of progenitor cell quality as well as quantity may be relevant to assessing CB blood collections.

The impact of antenatal and perinatal variables on cord blood haemopoietic stem/progenitor cell yield available for transplantation.

We investigated the impact of maternal and fetal variables on cord blood (CB) haemopoietic stem/progenitor cell content. These included maternal age, ethnic origin, parity, ABO and Rhesus D blood group, antenatal haemoglobin, alcohol and cigarette consumption at time of registration, mode of delivery, duration of the first and second stages of labour, gestational age, birth weight, cord pH and cord erythrocyte mean cell volume (MCV). Cord volumes and total nucleated cellularities (TNC) were recorded, the colony assay for granulocyte-macrophage colony-forming-cells (CFU-GM) was used to quantify the progenitor cells and the potential of CFU-GM to produce secondary colonies on replating was used as a measure of progenitor cell quality. We found: (1) significantly greater (P=0.04) volumes were collected from babies who weighed > or = 2.5kg versus babies with a birth weight <2.5kg; (2) significantly greater numbers of mononuclear cells (MNC) from mothers who drank 0-3 units versus those who drank > or = 4 units of alcohol weekly (P=0.03), and in babies with a cord pH < or = 7.1 v > 7.1 (P=0.02); (3) Significantly greater numbers of cord CFU-GM in mothers who drank 0-3 v > or = 4 units weekly (P=0.004) and smokers of > or = 10 v 0-9 cigarettes daily (P=0.02) and in spontaneous vaginal deliveries than assisted vaginal and caesarean deliveries (P=0.04), and (4) the potential of CFU-GM to produce secondary colonies was significantly greater in CB derived from Caucasians than from non-Caucasians ( P=0.02); in assisted vaginal delivery v spontaneous vaginal (P=0.02) and in deliveries with prolonged first stage of labour v short first stage of labour (P=0.04). We conclude that antenatal and perinatal variables may influence the CB stem/progenitor cell yield available for transplantation.

Incidence of objectively diagnosed thromboembolic disease in cancer patients undergoing cytotoxic chemotherapy and/or hormonal therapy.

From August 1993 to May 1994 there were 1505 inpatient and 2590 outpatient chemotherapy treatment episodes at the Clatterbridge Centre for Oncology. A total of 21 thromboembolic events, including two arterial events, were recorded among these patients at a median of 8 weeks from the start of treatment (range 0-14 weeks), and 2 episodes occurred at the time of first presentation. The median age of the patients developing thromboembolism was 53 (range 29-75) years, and there were 14 women and 7 men. In all, 13 of the events (62%) occurred in patients receiving inpatient treatment and 8 (38%), in outpatients. The incidence of thrombosis per treatment episode in inpatients was therefore 0.008 as compared with 0.003 in outpatients. The associated malignancies were breast cancer (5), testicular cancer (4), lung cancer (3), ovarian cancer (3) and non-Hodgkin's lymphoma (2), with bladder, colon, anal and brain cancer providing 1 case each. The following bulky pelvic or para-aortic disease was present in 9 patients: testicular cancer (3), ovarian cancer (3), lymphoma (2) and bladder cancer (1). In all, 20 of the 21 thrombotic episodes were successfully treated, with 1 patient dying from the complications of venous gangrene. Thromboembolic disease is a relatively common and important cause of morbidity and mortality in cancer patients that requires early recognition and treatment.

Hypersensitivity and cross-reactivity to cisplatin and analogues.

We report on a 49-year-old woman with relapsing ovarian cancer who developed a hypersensitivity reaction (HSR) to carboplatin and, subsequently, to cisplatin. This patient was known to be allergic to Co-Amoxiclav and talc, both giving rise to a transient macular skin rash, but had no other history of atopy. Similar cases, including some of life-threatening severity, have been reported in the literature. These severe reactions may prevent a small population of young patients from receiving effective therapy with cisplatin or its analogues, treatment known to be associated with a significant improvement in survival in germ-cell tumours, ovarian cancer and osteogenic sarcoma.

Delayed commencement of granulocyte colony-stimulating factor following autologous bone marrow transplantation accelerates neutrophil recovery and is cost-effective.

It is known that Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery following bone marrow transplantation (BMT), though the optimal timing is not clear. We have undertaken a pilot study in 19 recipients of autologous BMT for non-myeloid malignancy, in which G-CSF was commenced 10 (13 cases) or 7 (6 cases) days after BM infusion. These patients were compared with 18 historical controls, who did not receive G-CSF. The median time to achieve both 0.5 and 1.0 x 10(9) neutrophils/Litre was significantly shorter in the treated group (18 and 21 days respectively) than the control group (20.5 and 29 days; p = 0.03 and 0.02 respectively). No differences between the two groups were seen for the number of febrile days, days on antibiotics or the cost of the antibiotics. G-CSF-treated patients remained in hospital for significantly less time after marrow infusion (21 days compared to 29 days; p = 0.007). The cost of the G-CSF therapy was offset by the decreased bed utilisation, so that the median combined antibiotic, G-CSF and hospitalisation cost was 754 pounds less for G-CSF treated patients. It is concluded that delaying the commencement of G-CSF after autologous BMT accelerates neutrophil recovery, and may allow earlier discharge from hospital, whilst not adversely affecting the cost of the procedure.