This report describes studies investigating the use of a collagen binding assay to improve the laboratory monitoring of desmopressin (DDAVP) therapy in patients with von Willebrand's disease (vWD). We evaluated the response of seven patients with vWD (four type I, three type IIA) to DDAVP, administered using a standard protocol, by assessing levels of von Willebrand factor (vWF) and factor VIII, as well as performing skin bleeding times (SBT) prior to, and at sequential time points following, DDAVP administration. The study employed the following assays: von Willebrand factor antigen assay (vWF:Ag; determined by ELISA); a novel functionally based collagen binding assay (CBA; determined by ELISA); ristocetin cofactor assay (RCof; determined by platelet aggregometry); von Willebrand factor multimer analysis (using SDS-agarose gels); factor VIII coagulant (FVIIIC; determined by clotting assay); and factor VIII antigen (FVIIICAG; determined by ELISA). All patients showed an initial incremental increase in vWF/FVIII levels using all assays above, and some showed some correction in SBT. Although the absolute levels of vWF/FVIII antigen or activity varied between patients, the CBA was found to provide consistently the greatest proportional incremental increases (i.e., -fold) compared to baseline (pre-DDAVP) levels. Accordingly, we consistently observed an increase in the CBA to vWF:Ag ratio for all patients evaluated. This supplements previous findings that have suggested a unique ability of our CBA procedure to bind preferentially to higher molecular weight (i.e., more functionally active) forms of vWF. We therefore propose that the use of the above test combination (e.g., vWF:Ag plus CBA) may provide the basis for more accurate estimation of a patient's functional responsiveness to DDAVP therapy in future studies.

Objectives: To estimate the appropriateness of transfusions of platelets, fresh frozen plasma (FFP) and cryoprecipitate using National Health and Medical Research Council and Australasian Society for Blood Transfusion guidelines (NHMRC/ASBT 2002). Design and setting: Three separate retrospective surveys of medical records from 1 January to 31 August 2000 (1147 transfused patients) from 14 hospitals selected randomly from all public hospitals that use these blood products in New South Wales: five tertiary referral, five major metropolitan, and four major rural (base) hospitals. Main outcome measures: Proportion of potentially inappropriate transfusions. Results: 33% (136/414) of platelet, 37% (248/669) of FFP and 62% (37/60) of cryoprecipitate transfusions were assessed as inappropriate. By hospital type, 29% (75/259) of platelet transfusions were inappropriate at tertiary referral hospitals, 51% (40/78) at major urban hospitals, and 27% (21/79) at major rural hospitals. For FFP, 36% (112/313), 37% (80/216) and 39% (55/140) were inappropriate for referral, urban and rural hospitals, respectively. Cryoprecipitate was used almost exclusively at tertiary referral hospitals. Conclusions: In terms of the NHMRC/ASBT guidelines on use of blood products, there is considerable inappropriate transfusion of platelets, FFP and cryoprecipitate in NSW public hospitals.

Cabozantinib was associated with improved clinical outcomes versus everolimus in patients with advanced RCC, irrespective of prior therapy, including checkpoint inhibitor therapy.

Objectives To assess the appropriateness of red blood cell (RBC) transfusions and the effectiveness of an intervention to reduce inappropriate RBC transfusions. Design Medical record audit by hospital staff using a data form, before and after randomly allocated interventions (letter only or letter+visit). Criteria for assessing appropriateness of RBC transfusions were based on a systematic literature review. Setting Ten major urban hospitals in Sydney, New South Wales, in 1998 and 1999. Subjects Medical records of up to 120 patients at each hospital (n = 1117). Interventions Letter‐only (5 hospitals) — results of first audit at the hospital mailed to chief executive officer of that hospital; letter+visit (5 hospitals) — results of first audit at the hospital presented by the research team to a meeting of that hospital's staff, and then mailed to the chief executive officer. Main outcome measure Proportion of RBC transfusions assessed as inappropriate. Results At first audit, 35% of RBC transfusions were assessed as inappropriate. Small reductions in inappropriate transfusions were found at the second audit, but the change was significant only for the hospitals receiving the letter‐only intervention. About 5% of patients received a single RBC unit; 40% of single‐unit transfusions were inappropriate. More RBC transfusions were inappropriate in surgical patients than in those treated by other specialties. Conclusions About a third of RBC transfusions were assessed as inappropriate. The interventions had only a small effect on transfusion appropriateness.

Acquired deficiencies of, or inhibitors to, factor V are considered rare events. We report a series of 14 acquired factor V deficiencies, 10 of which were confirmed to have inhibitors to factor V, as identified within Australia in the past 5 years following a multi-laboratory investigation. The initial index case seen by one laboratory was followed within 4 months by a separate similar case. This prompted local contact with colleagues (n = 20) working in other haemostasis referral laboratories to identify the current case series. In total, nearly one-half of all haemostasis referral laboratories contacted had seen a case within the past 5 years. Clinical features and the apparent associated risk of bleeding complications generally varied, as did laboratory findings and the likely causal event. There were three females and 11 males. Age ranged from 44 to 95 years (median, 81 years). The level of inhibitor ranged from undetectable to over 250 Bethesda units. The probable cause leading to development of the inhibitors ranged from exposure to bovine thrombin, exposure to antibiotics, surgery and malignancy. Of additional interest was the apparent association of anti-phospholipid antibodies in many of the cases. For example, in the two similar index cases, with factor V inhibitor titres > 200 Bethesda units, high levels of anti-cardiolipin antibodies (> 70 GPL units) were also detected. Although less clear because of inhibitor interference, many of the cases also showed evident co-associated lupus anticoagulant activity. In conclusion, we report a series of factor V inhibitors recently identified within our geographic region that would represent an annual incidence of around 0.29 cases per million Australians. Although considered a rare finding, there is a high likelihood that most haemostasis referral laboratories will see a case every five or so years.

No abstract

SummaryThis is the first report of a method to assess the significance of numerical changes in the platelet count based upon a result exceeding the normal intra-individual variation in platelet numbers. Serial platelet counts from 3,789 subjects were analysed to determine the intra-individual variation in platelet numbers. A platelet count difference of 98 × 109/L in males was found to represent a change that would occur by chance in less than 1 in 1,000 platelet count determinations. Tables to determine the significance of platelet number variations, given N previous observations, are provided at two probability levels. The repeatability of the platelet count was calculated as 0.871 (males) and 0.849 (females) indicating that the heritability of platelet count is high and that the platelet count is predominantly genetically determined. A seasonal variation in platelet count was found with a ‘winter’ versus ‘summer’ difference of 5.10 × 109/L (males) and 5.82 × 109/L (females).

No abstract