The antithrombic drugs in clinical practice.

The rational use of antithrombic drugs centres on the fundamental differences in the pathogenesis of arterial or venous thrombosis. The major role of platelets in the development of occlusion in arteries contrasts with prominent fibrin deposition in the slower moving venous blood. Logically, antiplatelet agents are used to treat patients at high risk from arterial disease and anticoagulants for those with venous thrombo-embolism. These sound theoretical principles have been linked to steady improvement in diagnostic techniques, and there now exists an extensive literature on available drugs and their clinical evaluation. It is therefore surprising how little agreement exists on the practical use of the antithrombic drugs. In patients with coronary artery disease, secondary prevention of myocardial infarction is favourably influenced by administration of aspirin, dipyridamole or sulphinpyrazone. However, differences are not statistically significant so that confident recommendations for their use cannot yet be made. In mitral valve disease, anticoagulants are effective in reducing systemic thrombo-embolism; in patients with cardiac prostheses, dipyridamole should be added. In the cerebral circulation, vertebrobasilar and carotid ischaemia need to be distinguished and suitable lesions surgically corrected. Patients not undergoing endarterectomy are divided into two groups. In those with symptoms stable for more than 3 months, aspirin alone is sufficient; patients with recent deterioration or a shorter history are best treated with conventional anticoagulants followed by the addition of aspirin. In venous thrombo-embolic disease, heparin prophylaxis should be combined with reversal of identifiable risk factors. In treating the acute event, anticoagulation, with or without preceding thrombolytic therapy, is preferred. In addition, the clinician must select an antithrombic regimen o take into account the possibility of drug interaction, the need for and feasibility of laboratory monitoring, and the total number of medicines prescribed for the patient. Failure to restrict tablets to manageable numbers will lead to poor compliance and unpredictable therapeutic response.

Diagnostic value of trephine biopsy in bone disease.

A clinical diagnosis of myeloma was made in a 44-year-old woman with anaemia, a markedly raised erythrocyte sedimentation rate, osteolytic lesions in the pelvis, and a pathological fracture of the femur. Confirmatory trephine biopsy showed, instead of plasma cell infiltration, destruction of the normal micro-anatomy of the marrow with bridging fibrosis, gross osteoclastic proliferation, and areas of new bone formation. These are the features of hyperparathyroidism. Subsequently, a solitary adenoma of the parathyroid glands was demonstrated and resected. This case illustrates the value of examination of the trabeculae in trephine biopsy specimens in the diagnosis of bone disease.

Haematology Grand Rounds. Hairy cell leukaemia masquerading as malignant lymphoma.

Pancytopenia with massive splenomegaly, minimal lymphadenopathy and circulating atypical lymphoid cells with cytoplasmic projections characterize the lymphoproliferative disorder known as hairy cell leukemia, or leukaemic reticulo-endotheliosis. Many of the features of hairy cell leukaemia are shared with a malignant lymphoma of the B-cell type, from which it can be distinguished on a number of criteria, including histological examination of bone marrow, lymph nodes, liver and spleen. Recognition that this syndrome is not homogeneous is important, since in the B-cell tumour the clinical course is progressive, requiring chemotherapy which is usually effective; the disease is indolent in leukaemic reticulo-endotheliosis and drug treatment may actually shorten survival. The patient presented illustrates the ease with which this diagnostic error can arise, and the features separating these two unusual entities are reviewed.

8;21 translocation in myelodysplasia secondary to essential thrombocythemia.

A case is presented of a 73-year-old woman who received busulphan for essential thrombocythemia and subsequently developed a myelodysplastic syndrome (MDS), which transformed to acute nonlymphoblastic leukaemia within 1 month. Cytogenetic studies showed a 46,XX,t(8;21) (q22;q22) karyotype in all metaphases examined at diagnosis. The karyotypic abnormality is previously unreported in secondary myelodysplasia and may have specific clinical implications in this setting, such as early transformation to acute leukaemia and short survival. This finding contrasts with the generally favourable prognosis of the 8;21 translocation in patients with de novo acute nonlymphoblastic leukemia. A possible explanation for this difference may be the involvement of a committed progenitor in acute nonlymphoblastic leukaemia, while in myelodysplasia the more primitive multipotent stem cell may be affected.

Micro-angiopathic haemolytic anaemia and an unusual lactate dehydrogenase iso-enzyme pattern in metastatic adenocarcinoma. A case report.

Micro-angiopathic haemolytic anaemia is an unusual but well-recognized complication of metastatic adenocarcinoma. A young black man presented with red cell fragmentation, compensated disseminated intravascular coagulation and leuco-erythroblastosis. Metastatic adenocarcinoma of the stomach was suspected but only demonstrated at autopsy. An unusual finding was the elevation of the slow-moving lactate dehydrogenase iso-enzyme (LDH5) level in the plasma which was shown to be produced by metastatic tumour cells recovered from the bone marrow.

Primary shunt hyperbilirubinaemia: a variant of the congenital dyserythropoietic anaemias.

A 19 year old Mauritian male presented with episodic nausea, abdominal discomfort and jaundice. Unconjugated hyperbilirubinaemia and erythroid hyperplasia without dyserythropoiesis led to the diagnosis of primary shunt hyperbilirubinaemia. The similarity between congenital dyserythropoietic anaemia and this entity suggests that patients with these lesions can be considered within a single spectrum of disorders, characterized as congenital ineffective erythropoiesis.

A prospective analysis of prognostic factors in the myelodysplastic syndromes.

In view of the uncertainty regarding the natural history and management of individuals with the myelodysplastic syndromes, a prospective study of 43 consecutive and previously untreated patients was undertaken in order to identify haematological features that could predict for poor prognosis. A significant correlation between percentage of blasts in the bone marrow, maturity index and the number of cell lineages involved was demonstrated with both the risk of leukaemic transformation and survival. It remains to be determined whether further accumulation of data will result in similar predictive values for karyotypic analysis, in vitro bone marrow culture and the species of plasminogen activator secreted by the cells. Since treatment ranges from red cell transfusion and administration of maturation-inducing agents to aggressive cytotoxic chemotherapy or bone marrow transplantation, the development of predictive models, based on relevant prognostic factors, remains the most rational basis for choices between these various options.