Naomi Mackinlay

Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia

Hypogammaglobulinemia is a common complication of chronic lymphocytic leukemia (CLL), but the significance of immunoglobulin G (IgG) subclass deficiency is unknown. We analyzed the prevalence of immunoglobulins G, A and M, IgG subclass deficiency and infection in 150 patients with CLL. Low IgG, IgA and IgM levels were observed in 27.3%, 30.7% and 56.7% of patients, respectively. IgG subclass deficiency was frequent, with reduced IgG1, IgG2, IgG3 and IgG4 in 28%, 19.3%, 52% and 22.7% of patients, respectively. IgG subclass deficiency (total 64.6%) and hypogammaglobulinemia (27.3%) were more prevalent than clinically significant infection (16%). Recurrent or significant infections were seen in 24 patients (16%), of whom 50% had hypogammaglobulinemia but 100% had at least one IgG subclass deficiency, indicating that half the patients with infection had IgG subclass deficiency but normal total IgG level. Deficiencies of IgG3 and IgG4 were statistically associated with infection risk. Normal immunoglobulin and IgG subclass levels were seen in 26 patients (17%) and none had infections. IgG subclass deficiency is commonly observed in patients with CLL with both normal and reduced total IgG levels, and is associated with infection. Screening patients with CLL for IgG subclass deficiency may be a useful adjunct in stratifying their infection risk.

A survey of heparin monitoring in australasia

&NA; Full dose heparin therapy is monitored by a variety of laboratory methods, of which the activated partial thromboplastin time (APTT) is the most popular. A large number of APTT reagents are currently available, with different sensitivities to heparin evident in many. Within the literature it is apparent that there is a lack of consensus, and indeed some confusion, regarding the therapeutic ranges for the APTT for standard heparin therapy in the treatment of venous thromboembolic disease. Accordingly we conducted an Australasian survey to evaluate current laboratory and clinical practices in monitoring heparin therapy, to determine the extent of variation in the approach and to stimulate the process of standardisation of acceptable procedures and methodology. Results of the survey demonstrate that currently there is no uniform practice used to establish therapeutic ranges for monitoring standard heparin therapy. Furthermore, results suggest that current practice may lead to subtherapeutic anticoagulation in many laboratories.

Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment‐free and overall survival in Chronic Lymphocytic Leukaemia

Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment‐free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.

Genetic prion disease-associated myelodysplasia and SIADH in siblings.

F. C. F. Chang, Y. Berman, M. E. Buckland, N. MacKinlay, A. McGlade, S. Collins and K. Ng Department of Neurology, Department of Clinical Genetics, Royal North Shore Hospital and the University of Sydney, Sydney, NSW; Department of Neuropathology, Royal Prince Alfred Hospital and the University of Sydney, Sydney, NSW; Department of Haematology, Royal North Shore Hospital and the University of Sydney, Sydney, NSW; and Australian National CJD Registry, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia

Genetic analysis of Diffuse Large B-cell Lymphoma occurring in cases with antecedent Waldenström Macroglobulinaemia reveals different patterns of clonal evolution

Fischer, K., van der Bom, J.G., Molho, P., Negrier, C., Mauser-Bunschoten, E.P., Roosendaal, G., De Kleijn, P., Grobbee, D.E. & van den Berg, H.M. (2002) Prophylactic versus on-demand treatment strategies for severe haemophilia: a comparison of costs and long-term outcome. Haemophilia, 8, 745–752. Foley, C.J., Nichols, L., Jeong, K., Moore, C.G. & Ragni, M.V. (2010) Coronary atherosclerosis and cardiovascular mortality in hemophilia. Journal of Thrombosis and Haemostasis, 8, 208– 211. Larsson, S.A. (1985) Life expectancy of Swedish haemophiliacs, 1831-1980. British Journal of Haematology, 59, 593–602. Lovdahl, S., Henriksson, K.M., Baghaei, F., Holmstrom, M., Nilsson, J.A., Berntorp, E. & Astermark, J. (2013) Incidence, mortality rates and causes of deaths in haemophilia patients in Sweden. Haemophilia, 19, 362–369. Mannucci, P.M. & Mauser-Bunschoten, E.P. (2010) Cardiovascular disease in haemophilia patients: a contemporary issue. Haemophilia, 16 (Suppl 3), 58–66. Martin, K. & Key, N.S. (2016) How I treat patients with inherited bleeding disorders who need anticoagulant therapy. Blood, 128, 178–184. Rizwan, I., Minuk, L., Jackson, S. & Iorio, A. (2015) Cardiovascular disease prevalence and relevance in haemophilia: a scoping review. Haemophilia, 21, e156–e166.