The blood in systemic disease

Few diseases do not produce some alteration in the blood, and changes in the blood may give the first indication of many nonhaematological disorders.

Malignant disease

Malignant disease can cause protean haematological manifestations, including (1) leucoerythroblastic anaemia—the appearance of immature myeloid cells and nucleated red cells is a common phenomenon in disseminated malignancy, and occasionally there is a leukaemoid reaction; (2) anaemia of chronic disorders—see Chapter 22.5.5; (3) increase of the erythrocyte sedimentation rate; (4) thrombocytosis—of unknown cause, but often the first manifestation of cancer; (5) thrombocytopenia—may be due to widespread infiltration of the bone marrow, but more frequent in association with autoimmune effects of lymphomas and other tumours; (6) activation of blood coagulation pathways—this may cause thromboses as well as disseminated intravascular coagulation; adenocarcinomas that release tissue factor are characteristically responsible.

Specific tumours can cause particular haematological manifestations, most commonly iron deficiency anaemia attributable to gastrointestinal malignancy as a result of chronic haemorrhage, and much less commonly (1) microangiopathic haemolytic anaemia—may be caused by mucin-secreting adenocarcinomas; (2) autoimmune haemolytic anaemia—may occur with a wide variety of tumours; (3) pure red-cell aplasia—seen in thymoma; (4) secondary polycythaemia—caused by erythropoietin-secreting tumours, e.g. of cerebellum and kidney.

Other associations between malignancy and haematological disorders include (1) pernicious anaemia—associated with gastric cancer; (2) the effects of treatments for cancer—chemotherapy frequently causes various cytopenias and other toxic effects, including haemolysis.

Infection

Acute bacterial infections—these cause neutrophilia, but occasionally in severely ill patients there is an inadequate response or frank neutropenia, which is characteristic of salmonellosis, brucellosis, rickettsial infections, disseminated tuberculosis, or histoplasmosis.

Chronic bacterial infections—these characteristically induce the anaemia of chronic disorders, but tuberculosis may also cause leukaemoid reactions, pancytopenia, and myelofibrosis, and should be considered in any patient with an unexplained and atypical myeloproliferative disorder.

Virus infections—these generally cause mild neutropenia with lymphocytosis. Conditions of particular note include (1) Epstein–Barr virus—often associated with atypical lymphocytes, which are also found in other viral infections (e.g. cytomegalovirus). (2) Rubella and measles—often cause thrombocytopenia, and occasionally there is bleeding due to disseminated intravascular coagulation. (3) HIV/AIDS—may cause marked anaemia related to the chronic disorder, but examination of the bone marrow frequently shows dyserythropoiesis, which may be related to poor nutrition, drug toxicity and opportunistic infection. Progressive immunodeficiency is associated with lymphoma. (4) Aplastic anaemia—may occur in parvovirus B19 infection and (rarely) hepatitis B infection.

Protozoal and helminthic infections—these include (1) Malaria—can cause a range of manifestations including (a) severe anaemia of complex aetiology—typically in children; (b) thrombocytopenia—a common finding; (c) neutropenia—a common finding; (d) intravascular haemolysis—may be associated with glucose-6-phosphate dehydrogenase deficiency; (e) disseminated intravascular coagulation—probably uncommon; (f) tropical splenomegaly syndrome—can cause pancytopenia due to hypersplenism. (2) Other conditions—these include (a) Leishmaniasis—causes pancytopenia with prominent neutropenia in the early phase of infection; anaemia is due to an inappropriate marrow response and hypersplenism. (b) Hookworm infestation—one of the commonest causes of iron deficiency anaemia in the world. (c) Eosinophilia—characteristic of helminth infestation, particularly during the systemic phase.

Rheumatic and autoimmune disorders

Rheumatoid arthritis—haematological manifestations include (1) anaemia—largely attributable to the response to chronic disease, but iron deficiency due to medication-related blood loss is common; (2) Felty’s syndrome—hypersplenism and immune destruction of neutrophils causes pancytopenia and marked neutropenia.

Other disorders—these include (1) systemic lupus erythematosus—anaemia is common and may be related to chronic illness, gastrointestinal blood loss attributable to medication, renal impairment, and autoimmune haemolysis; mild thrombocytopenia occurs in 10 to 25%; lupus anticoagulants and associated anticardiolipin antibodies may be associated with venous thromboembolism, arterial thromboembolism, an increased fate of fetal loss, or thrombocytopenia. (2) Polymyalgia rheumatica and temporal arteritis—may present with severe anaemia of chronic disorders and marked elevation of the erythrocyte sedimentation rate.

Other conditions

These include (1) Renal disease—complications include anaemia, mainly due to erythropoietin deficiency, and also defective haemostasis with bleeding tendency due to abnormal platelet function. (2) Gastrointestinal disease—haematological manifestations include iron deficiency due to bleeding, also malabsorption of iron, folate, and/or vitamin B₁₂. (3) Liver failure—associated with macrocytic anaemia, also with microcytic anaemia due to blood loss from peptic ulceration or bleeding varices; bleeding and haemostatic failure are common, attributable to both thrombocytopenia due to hypersplenism and failure of hepatic formation of coagulation factors V, VIII, IX, X, XI, prothrombin, and fibrinogen. (3) Alcohol—has numerous adverse effects on the blood: macrocytosis and thrombocytopenia are frequent; nutritional deficiencies of iron and folate may complicate the picture; may have direct toxic effects on megakaryocytes and impairs neutrophil function.

Numerous specific abnormalities of the blood occur in other systemic diseases, e.g. in pulmonary eosinophilia, mast-cell and neurological syndromes due to neuroacanthocytosis, and abetalipoproteinaemia.