Chemical and physical agents

Oxidative haemolysis

Oxidative substances may cause haemolysis in people with normal red cell metabolism and normal HbA if the oxidative stimulus is large enough. The major causes of oxidative haemolysis in normal subjects are shown in Table 10.7. The clinical features of this condition are dependent on the main sites of oxidative attack, whether on the membrane of the red cell, the globin chains or the haem group.

Figure 10.5 Oxidative haemolysis caused by drug (phenacetin). Note red cells with contracted haemoglobin.

stop the treatment unless the anaemia is severe. A dose reduction may sometimes be needed.

Methaemoglobinaemia is uncommon unless the patient is partially deficient in NADH methaemoglobin reductase. The gene for this abnormality may not be very uncommon, and it may account for some people becoming cyanosed after taking dapsone-containing antimalarial preparations.

Chronic intravascular haemolysis with Heinz bodies

Dapsone and Salazopyrin (salicylazosulphapyridine) will cause oxidative intravascular haemolysis in normal subjects if taken in high enough dosage. Red cells show the 'bite' abnormality of the chemically damaged cell (Figure 10.5). Heinz bodies may be absent or scanty in patients with an intact spleen. Dapsone is used in the treatment of G6PD-deficient subjects with leprosy and in the treatment of dermatitis herpetiformis, in which functional hyposplenism occurs; Heinz bodies appear in the latter case, acute intravascular haemolysis in the former.

Haemosiderinuria may be detected in patients taking these drugs, and there may be polychromasia and macrocytosis. Haemolysis is usually well compensated and there is no need to

Methaemoglobinaemia with or without haemolysis

Nitrites in water or vegetable juices may cause methaemoglo-binaemia in infants who have a physiological impairment of the reducing systems. Well water that comes from land with an excess of nitrites and which is used to reconstitute artificial feeds has produced cyanosis in infants. Cases have also been described following the enthusiastic feeding of juice from carrots grown on organically fertilized land and of spinach juice (spinach has a high concentration of nitrogen-fixing bacteria on its leaves).

Nitrate drugs, for example amyl nitrate, also produce methae-moglobinaemia and have proved fatal when taken in high enough dosage for 'recreational' purposes.

Table 10.7 Substances causing oxidative haemolysis and/or methaemoglobinuria in normal people.

Substance

Use

Remarks

Dapsone

Leprosy; dermatitis herpetiformis

Chronic haemolysis; slow acetylators more susceptible

Maloprim

Antimalarial

Methaemoglobinaemia in NADH-MetHb

reductase-depleted subjects

Salazopyrine

Ulcerative colitis

Chronic intravascular haemolysis

Phenazopyridine

Analgesic in urinary tract infections

Methaemoglobinaemia

Menadiol

Water-soluble vitamin K analogue

Haemolysis/kernicterus in infants

Nitrites

Fertilizer; present in well water and some vegetable juices

Methaemoglobinaemia in infants

Nitrates, 30 g

Amyl nitrate, butyryl nitrite; abused recreationally

Acute i.v. haemolysis; renal failure; fatal

Arsine

Gas produced in smelting and other industrial processes

Acute i.v. haemolysis; renal failure

Water-soluble analogues of vitamin K (menadiol sodium diphosphate) cause haemolysis with or without methaemoglo-binaemia in infants and in utero if given to the mother during the third trimester. Fat-soluble vitamin K preparations must be used if required in these situations.

Methaemoglobinaemia due to oxidative drugs may be treated with intravenous methylene blue in doses of 1-2 mg/kg. Ascorbic acid by mouth may also be used. These measures are ineffective in G6PD-deficient patients and when very strong oxidant substances are implicated. In these circumstances, methylene blue should be avoided because it acts as an oxidant and makes the condition worse.

Acute intravascular haemolysis, methaemoglobinaemia and renal failure

These conditions occur following exposure to strong oxidizing substances that are found mainly in industrial or horticultural pursuits, e.g. sodium chlorate is a popular weed killer and arsine is a gas that is produced in various industrial settings. Acute intravascular haemolysis and haemoglobinuria develop. The serum becomes brown, often very dark, so that blood cells cannot be seen in anticoagulated preparations, due to the presence of methaemalbumin, methaemoglobin and free haemoglobin. Oliguric renal failure usually develops over about 24 h. The blood film shows microspherocytosis and bizarre forms.

Plasma exchange and renal dialysis are the mainstays of treatment, methylene blue being ineffective. Poisoning with arsine is usually reversible with these measures. Chlorate poisoning is more difficult, 30 g being a generally fatal dose. It is mostly ingested deliberately in suicide attempts.

Thermal injury

Normal red cells when heated in vitro show no changes when heated to 46°C for 1 h but show temperature- and duration-dependent changes above 47-50°C. Some hereditary membrane defects produce red cells that have increased thermal fragility (see Chapter 8).

Haemolysis following burns

Severe burns may be accompanied by intravascular haemolysis with haemoglobinuria. The intravascular haemolysis is related to the extent and severity of the burns. The gross haemoglo-binuria occurs over the first 24 h after the burns and ceases thereafter. The blood film shows spherocytosis and schistocytes, the morphological abnormalities reflecting the thermal damage and the amount of lysis. Prolonged anaemia post burning is related to inflammation, occult blood loss and infection rather than haemolysis.

Acquired disorders of the red cell membrane

The mature red cell does not have the capacity for the repair of its membrane. The lipids of the membrane are in equilibrium with the lipids of the plasma and changes in the ratio of free cholesterol to phospholipids in plasma may affect the red cell shape and, in some instances, lead to haemolysis. This is most commonly seen in liver disease, but other inherited lipid disorders may affect the red cell secondarily.

Liver disease

Some degree of shortening of the red cell survival occurs in most cases of acute hepatitis, cirrhosis and Gilbert's disease, but anaemia is not present and there is only a slight rise in reticulo-cytes, which may not be detectable. Biliary obstruction is associated with the appearance of target cells and fulminant hepatitis with acanthocytosis, both consequent on changes in the plasma lipid composition.

Zieve's syndrome is an uncommon disorder, seen mainly in alcoholics. It comprises intravascular haemolysis and acute abdominal pain. These patients usually have cirrhosis and jaundice. The cause is unknown but is probably related to lipid changes in the blood. Spherocytes are seen in the peripheral blood.

Wilson's disease may present as acute intravascular haemolysis. This is probably not a membrane disorder but is consequent on the high levels of copper ions in the blood. The haemolysis may antedate the development of hepatic or neurological features, but Keyser-Fleischer rings are usually present. The blood film may show spherocytosis. The diagnosis is made once the condition is suspected. Apart from caeruloplasmin deficiency, patients have a specific aminoaciduria.

Hereditary acanthocytosis (a-P-lipoproteinaemia)

This rare inherited deficiency of low-density lipoproteins is characterized by retinitis pigmentosa, steatorrhoea, ataxia and mental retardation. The haemolysis that occurs is of minor importance to such patients, but the blood film may indicate the diagnosis, with the red cells showing marked acanthocytosis.

Vitamin E deficiency

Deficiency of vitamin E may occur in infants who are fed a diet rich in polyunsaturated fatty acids. There is haemolysis with contracted cells and a thrombocytosis. Oedema may be present. Vitamin E is an antioxidant, and oxidative damage to the red cell membrane is thought to be the cause of the haemolysis.

Curing Eczema Naturally

Curing Eczema Naturally

Do You Suffer From the Itching, Redness and Scaling of Chronic Eczema? If so you are not ALONE! It strikes men and women young and old! It is not just

Get My Free Ebook


Post a comment