Renal disease

Diseases of the kidney are associated with a remarkably wide range of possible haematological abnormalities (Table 48.1).

Anaemia is almost inevitable in chronic renal failure. The pathogenesis is complex but impaired erythropoietin production is the principal cause. Other possible contributory factors include the release of inhibitors of erythropoiesis, mild haemolysis and iron deficiency. The anaemia of renal failure is typically normocytic and normochromic. A characteristic finding in the blood film is the presence of burr cells (Fig 48.1). The best treatment of anaemia is resolution of the underlying renal problem (e.g. by transplantation), but where this is not feasible, recombinant erythropoietin is the treatment of choice. Intermittent bolus administration generally leads to a marked improvement in anaemia and transfusion independence. A failure of the anaemia to respond to erythropoietin should prompt a search for other aetiologies such as iron deficiency.

Paradoxically, some forms of renal disease can lead to increased red cell production and clinical polycythaemia (see Table 48.1). This arises either from inappropriate secretion of erythropoietin by a kidney tumour or from local renal hypoxia promoting erythropoietin release from normal cells. Polycythaemia can be the presenting feature of renal carcinoma and rapid identification of the malignancy may allow curative surgical treatment. Benign diseases such as polycystic disease and hydronephrosis probably cause polycythaemia by inducing renal ischaemia. The polycythaemia of renal disease is not an appropriate physiological response and patients with high haematocrits can derive benefit from regular venesection.

Chronic renal failure is also associated with a large number of possible platelet and coagulation abnormalities. The increased risk of bleeding in these patients is generally caused by the complex interaction of abnormalities shown in Table 48.1. Anaemia tends to worsen bleeding by interfering with the normal interaction between platelets and vascular endothelium.

Liver disease and alcohol

Significant liver disease is associated with haemostatic problems (see p. 77) and red cell abnormalities including macrocytosis and target cells. Excessive alcohol consumption commonly causes macrocytosis and thrombocytopenia.

Malignancy

Anaemia is seen in around half of patients with non-haematological malignant tumours. The anaemia of chronic disease is the most common aetiology (p. 36) but other causes include chemotherapy, blood loss, haemolysis and marrow infiltration. Invasion of the bone marrow by solid tumours can result in a pancytopenia and a characteristic leucoerythroblastic blood picture with circulating nucleated red cells and myelocytes (Fig 48.2a). Clumps of malignant cells may be seen in a bone marrow aspirate but a bone marrow trephine is a more reliable way of demonstrating solid malignancy (Fig 48.2b).

Malignancy can be associated both with a hypercoagulable state and a bleeding tendency. The presence of hypercoagulability was first suggested by the increased incidence of deep vein thrombosis and pulmonary embolism seen in cancer patients. The mechanism is thought to be activation of the normal clotting system with low-grade intravascular coagulation and secondary fibrinolysis. In the laboratory, common findings are elevated levels of clotting factors and a shortened prothrombin time and activated partial thromboplastin time. It is presumed that cancer cells secrete thromboplastin which initiates clot formation. Treatment of venous thrombosis in malignancy is difficult, as anticoagulant control is often poor. Low molecular weight heparin is generally preferred to warfarin.

Disseminated intravascular coagulation (DIC) can complicate malignancy. It may be an acute haemorrhagic state but is more often a chronic low-grade disorder with no bleeding. It is particularly likely to accompany carcinomas of the prostate, stomach, colon, breast, ovary, lung, gallbladder and melanoma. DIC is further discussed on page 76.

Connective tissue disorders

Systemic disorders such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and mixed connective tissue disease often lead to abnormal blood counts. In practice the most common finding, particularly in rheumatoid arthritis, is the anaemia of chronic disease. Immune thrombocytopenia is more often seen in SLE and this heterogeneous disorder may also be complicated by the presence of the lupus anticoagulant (p. 79). Neutropenia can arise in several connective tissue disorders; the triad of long-standing rheumatoid arthritis, splenomegaly and neutropenia is termed Felty syndrome. There may be a small increased risk of haematological malignancy in patients with rheumatoid arthritis. In Sjögren’s syndrome there is a substantially increased risk of non-Hodgkin’s lymphoma.

Infections

Infections are probably the most common cause of abnormal blood counts in a typical haematology laboratory. Different infections are associated with different abnormalities but it is possible to make some generalisations.

Bacterial infections commonly cause a neutrophil leucocytosis. The neutrophils are classically ‘left-shifted’ (i.e. reduced nuclear segmentation) with increased cytoplasmic granulation (toxic granulation). Very severe bacterial infections such as disseminated tuberculosis can induce a leukaemoid reaction with immature myeloid cells appearing in the blood.

Viral infections most commonly cause a transient lymphocytosis with reactive changes in the cells. Two types of viral infection merit more detailed description: infectious mononucleosis and HIV infection.