Lymphocytopenia in a hospital population--what does it signify?

BACKGROUND: Lymphocytopenia is a common finding in hospital patients especially since the advent of automated differential leukocyte counters. The causes and significance of lymphocytopenia are generally poorly understood. There has been no large-scale study of its significance for 25 years. The HIV epidemic, and the recently described idiopathic CD4+ T-lymphocytopenia have raised interest in this finding. AIMS: To describe the spectrum of lymphocytopenia in an adult teaching hospital and investigate its clinical significance. METHODS: Using the available computer facilities, patients with significant lymphocytopenia (< 0.6 x 10(9)/L) were identified over a 102 day period and diagnoses, operations and medication lists obtained. Where necessary, patient histories were examined to supplement the above information. If feasible, previous and subsequent lymphocyte counts were checked to establish if the lymphocytopenia were temporary or longstanding. RESULTS: One thousand and forty-two patients were identified, with a mean age of 59.6 years, of whom 563 were male, and 757 were inpatients. Thirty-six patients were pancytopenic. We checked previous and subsequent counts for 698 patients and found 45 patients who were consistently lymphocytopenic, some for more than ten years. Thirty-four patients with previously normal counts remained lymphocytopenic throughout follow up, while 457 had at least one subsequent lymphocyte count > 1 x 10(9)/L. We found only one patient who was suspected of having idiopathic CD4+ T-lymphocytopenia. Patients fell into several categories (with some overlap): bacterial/fungal sepsis (250), post-operative (228), corticosteroid therapy (definite 159, suspected 53, inhaled steroids alone 14), malignancy (174 definite, six probable), cytotoxic therapy and/or radiotherapy (90), trauma or haemorrhage (86), transplants (73-38 renal and 35 bone marrow), 'viral infections' (26) and HIV infection (13). Thirty-four patients died within the study period. CONCLUSIONS: Lymphocytopenia in hospital patients is most frequently reversible, and due to acute illness, notably sepsis and trauma (including surgery). Malignancy, with or without chemotherapy, and steroid use are also common causes, but HIV infection is a relatively uncommon cause in our hospital.

Natural anticoagulants and the liver.

The regulation of blood coagulation is dependent on a complex interplay between procoagulant, anticoagulant and fibrinolytic proteins. Most of these proteins are synthesised in the liver and their levels are altered in patients with liver disease. The liver also plays an important role in the regulation of haemostasis throughout the clearance of activated clotting factors. It is therefore not surprising that the critically balanced coagulation system is dysregulated in patients with liver disease. In moderate liver failure bleeding disorders predominate, whereas in more advanced liver disease intravascular coagulation is commonly observed and contributes to the overall dysregulation of blood coagulation. In some patients, liver disease can be primarily caused by an abnormality of the coagulation system. These patients usually have a hypercoagulable state caused by a deficiency of a component of the natural anticoagulant system. These include protein C, protein S and antithrombin III. More recently, activated protein C resistance caused by a point mutation in the Factor V gene has been identified as an important risk factor for thrombosis. In these patients the abnormal Factor V is resistant to cleavage by activated protein C resulting in ongoing uncontrolled procoagulant drive. Both hepatic and portal vein thrombosis have been reported in these patients. Appropriate management of these patients should include a thorough assessment of their natural anticoagulant proteins and exclusion of activated protein C resistance as the cause of their thrombotic disorder.

Primary Sjögren's syndrome and gamma heavy chain disease.

We describe a patient who has primary Sjögren's syndrome associated with asymptomatic gamma heavy chain disease and a tubulointerstitial nephritis. Sjögren's syndrome is known to be complicated by lymphoproliferative disorders and tubulointerstitial nephritis but gamma heavy chain disease is rare (approximately 100 cases described). There is one previously reported case of gamma heavy chain disease associated with primary Sjögren's syndrome and 2 cases associated with secondary Sjögren's syndrome. Our patient and the 3 other patients described in the literature did not have evidence of an underlying lymphoproliferative disorder.

A comparison of Epstein-Barr virus-specific T-cell immunity in malaria-endemic and -nonendemic regions of Papua New Guinea.

Epstein-Barr virus genome-positive Burkitt's lymphoma is endemic in Africa and Papua New Guinea and in both countries the tumour is restricted to regions with holoendemic malaria. The present work has compared groups of healthy indigenous individuals living in malarious and non-malarious regions of Papua New Guinea for Epstein-Barr virus-specific T-cell-mediated immunity using the in vitro regression assay. Residents of the malarious region (55 tested), when compared with either residents of the non-malarious area (35 tested) or Caucasian controls (27 tested) showed a significant (p less than 0.0001) impairment of virus-specific T-cell immunity but no obvious disturbance (p greater than 0.05) of anti-viral antibody titres. These results may be important in explaining the postulated role of malarial infection as a co-factor in the pathogenesis of Burkitt's lymphoma.

Immunoprecipitation of biosynthetically labelled, stage-specific proteins from cultured Plasmodium falciparum using inhibitory human sera.

Proteins from synchronized continuous cultures of Plasmodium falciparum were biosynthetically labelled with [35S]methionine at ring, trophozoite, and schizont stages. Several proteins appeared to be synthesized predominantly at one stage only, especially the schizont stage. Immunoprecipitation using inhibitory human sera revealed that a variety of proteins, from all stages of parasite growth, were recognized. More proteins, especially those with high molecular weight, were precipitated from the schizont stage than from ring and trophozoite stages, but two major proteins (MW or approximately 70,000 daltons and or approximately 45,000 daltons) were recognized in all three stages.

Ovalocytosis in Papua New Guinea -- dominantly inherited resistance to malaria.

Analysis of ovalocytosis in families has demonstrated dominant inheritance. This conclusion is based on finding ovalocytic children of ovalocytic Melanesian mothers and normocytic Caucasian fathers. Inheritance of resistance to thermal deformation and to crenation upon storage correlated with inheritance of ovalocytic erythrocyte morphology. The latter was associated with in vitro resistance to invasion by P. falciparum.