Pathology tests: is the time for demand management ripe at last?

With the ever increasing demands for pathology testing within the National Health Service there is a need to manage the demand for these tests. This review discusses strategies for the demand management of requests made by clinicians in the disciplines of biochemistry, haematology, and microbiology. The various approaches that have been used to manage demand will be described, along with specific clinical strategies for demand management.

Warfarin-induced skin necrosis associated with Factor V Leiden and protein S deficiency.

Thrombotic events are rare complications during anticoagulation therapy. The thrombosis varies from localized cutaneous involvement to catastrophic thromboembolism and is usually associated with an underlying thrombophilia. We describe a patient who developed skin necrosis during warfarin treatment for a pulmonary thromboembolism. The management was complicated by the development of heparin-induced thrombocytopenia and further thrombotic events. Thrombophilia screen demonstrated the presence of protein S deficiency and Factor V Leiden as the prothrombotic factors, together with the demonstration of antiplatelet factor 4 antibodies, which confirms the diagnosis of heparin-induced thrombocytopenia (type II). Reinstitution of warfarin at a low loading dose was successful without the recurrence of skin lesions nor any further thrombosis.

Prevalence and molecular basis of alpha thalassaemia in British South Asians.

OBJECTIVES: To determine the prevalence and molecular basis of alpha thalassaemia in the British South Asian population, and the implications for genetic screening for haemoglobin disorders. METHODS: 397 South Asian Subjects were screened for haemoglobinopathy with measurement of bull blood count, haemoglobin electrophoresis, haemoglobin A2 quantification, and plasma ferritin determination. alpha Globin gene mapping was successfully performed on 266 stored buffy coat samples using a Southern blot technique after hybridisation with Bg/II and BamHI. RESULTS: Of the 266 subjects in whom gene mapping was performed, 28 had a single alpha+ thalassaemia deletion and one was homozygous for this deletion (gene frequency 0.056). Half of the heterozygotes had normal mean cell haemoglobin (MCH) values. A further 16 subjects had probable non-deletional alpha+ thalassaemia. None had alpha 0 thalassaemia. CONCLUSIONS: alpha Thalassaemia is by far the commonest haemoglobinopathy in British South Asian subjects, but is not a cause of serious genetic risk. Screening and counselling should focus on subjects with more marked red cell hypochromia (MCH < 25 pg), thus concentrating resources on subjects of different ethnic origins who may carry the alpha 0 thalassaemia gene.

Homozygous protein C deficiency--management with protein C concentrate.

UNLABELLED: 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 administered 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. CONCLUSION: Infusion of Pr C is a safe and efficient way of treating infants with homozygous Pr C deficiency in the medium term.

Zinc protoporphyrin assays in patients with alpha and beta thalassaemia trait.

AIMS: To determine the value of the red cell distribution width (RDW) and erythrocyte zinc protoporphyrin (ZPP) concentration in discriminating between iron deficiency, and beta and alpha thalassaemia in a mixed urban Asian population. METHODS: The RDW and ZPP concentrations were measured in 1412 subjects attending for outpatient phlebotomy, with classification into diagnostic groups on the basis of haemoglobin, mean cell haemoglobin, ferritin, HbA2 and haemoglobin electrophoresis. RESULTS: Non-parametric 95% reference ranges for RDW were 11.7-15.7% and for ZPP 38-104 mumol/mol haem. Both RDW and zinc protoporphyrin rose with increasing severity of iron deficiency, but were also raised in significant numbers of subjects with beta and probable alpha thalassaemia. CONCLUSIONS: Measurements of RDW and ZPP do not differentiate between alpha or beta thalassaemia trait and moderate degrees of iron deficiency (hypochromasia without anaemia). ZPP is a more accurate indicator of iron deficiency than RDW and concentrations above 150 mumol/mol haem strongly suggest iron deficiency, usually with anaemia, rather than thalassaemia.