Intravascular haemolysis

Intravascular haemolysis, such as paroxysmal noctural haematuria (kidney)... 

The hematopoietic toxicity includes agranulocytosis, thrombocytopenia and rarely aplastic anaemia and in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, sulfonamides may cause intravascular haemolysis. 

Sharma BK, Singhal PC, Chugh KS. 1978. Intravascular haemolysis and acute renal failure following potassium dichromate poisoning. Postgrad Med J 54 414-415. 

Forbes CD, Craig JA, Mitchell R, McNicol GP. Acute intravascular haemolysis associated with cephalexin therapy. Postgrad Med J 1972 48(557) 186-8. 

Kumana CR, Chan GT, Yu YL, Lauder IJ, Chan TK, Kou M. Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol. Br J Clin Pharmacol 1990 29(3) 347-53. 

Criel A, Verwilghen RL. Intravascular haemolysis and renal failure caused by intermittent rifampicin treatment. Blut 1980 40(2) 147-50. 

Other reported features include disorientation (Moschl, 1938 Kaszas and Papp, 1960 Malizia et al, 1977 Levin et al, 2000), drowsiness (Koch and Caplan, 1942), confusion (Wedin et al., 1986 Koch and Caplan, 1942), lightheadedness (Challoner and McCarron, 1990), muscle cramps (Kopferschmitt et al., 1983 Bispham, 1903 Rauber and Heard, 1985), convulsions (Moschl, 1938), intravascular haemolysis (Malizia et al, 1977), bradycardia (Challoner and McCarron, 1990), hypertonia (Moschl, 1938 Rauber and Heard, 1985), miosis (Malizia et al, 1977), mydriasis (Hutchinson, 1900 Balint, 1974) and blurred vision (Kopferschmitt et al, 1983). 

Muscle is the only source of CK and by measuring the isoenzyme CK-MB one can determine whether or not cardiac muscle is involved. If the liver is involved then the serum yGT should be increased as this is one of the most sensitive indicators of liver disease. LDH isoenzyme analysis will help identify erythrocyte damage as a possible source for some of the LDH and AST activity. In haemolytic disorders, one would expect a reticulocytosis and intravascular haemolysis will lead to a low serum haptoglobin level. These investigations will help identify whether or not erythrocytes have contributed to the serum enzymes. 

Acute intravascular haemolysis in glucose-6-phosphate dehydrogenase deficiency. 

Intravascular haemolysis due to glucose-6-phosphate dehydrogenase deficiency in a patient with aluminium phosphide poisoning. 

Acute intravascular haemolysis in glucose-6-phosphate dehydrogenase deficient patients following ingestion of herbal broth containing Acalypha indica. 

Serious and potentially life-threatening intravascular haemolysis and renal failure may develop rarely after the long-term use of mitomycin and fluorouracil. 

Jones BG, Fielding JW, Newman CE, Howell A, Brookes VS. Intravascular haemolysis and renal impairment after blood transfusion in two patients on long-term 5-fluccouracil and mito-mycin-C, Lancet 9%0) i, 1275-7. 

Lambden SP, Akeru J, Barrett NA. Acute intravascular haemolysis associated with intravenous administration of meropenem in a sixty four year old man. Can J Clin Pharmacol 2010 17(1) e64-6. 

Haem which has been oxidized and contains iron in the ferric state. In plasma, haematin can combine with albumin to form methaemalbumin. Haematin is released from red cells inpatients with intravascular haemolysis and in methaemoglobinaemia. 

This can occur as a result of intravascular haemolysis (see abov< or as a result of bleeding within the urinary tract, when inta< erythrocytes can appear in the urine. 

A combination of haematin (oxidized haem, containing iron in the ferric state) and albumin. It is found in the blood when there is intravascular haemolysis and in cases of acute haemorrhagic pancreatitis. It can be identified in blood by its spectral characteristics or by Schumm s test, in which an albumin haemo-chromogen, which has a distinctive absorption spectrum, is formed. 

A prospective open-label, randomised trial comparing 14days of primaquine (0.25 mg base/kg) with either artensunate-amodiaquine or dihydroartemisinin-piperaquine (DHP) for the treatment of uncomplicated monoinfection with Plasmodium vivax malaria was performed Patients were randomised and given treatments without testing for G6PD status. Of the 331 patients, intravascular haemolysis occurred in 5 patients, of which 3 were males hemizygous for the G6PD-Mahidol mutation. Minor side effects were more frequent with artensunate-amodiaquine. 

Comparative studies The FDA issued a black-box warning in 2010 in response to reports of intravascular haemolysis. Authors reviewed data from the Pediatric Health Information System, a database of inpatient data from 43 paediatric hospitals in the United States, and examined clinical practice before (January 2008 xmtil February 2010) and after (April 2010 xmtil December 2011) the FDA black-box warning [117 ]. They identified a statistically significant decrease in the percentage of ITP admissions in which anti-D was used (11.4% vs 9% 325 vs 198, p = 0.005), a statistically significant increase in the number of anti-D admissions with urinalysis (34% vs 59.1% 110 vs 117, p< 0.001), yet a similar incidence of complications. 

Viral infection The authors report a case in which a child became infected with Epstein-Barr virus developed immune thrombocytopenic purpura, and treatment with anti-D Ig caused intravascular haemolysis as well as acute kidney injury [118 ]. Although some degree of extravascular haemolysis is expected, this case is tmusual because of tile severity and intravascular nature. The authors speculate that the use of intravenous anti-D triggered an xmusual virus-induced immune response that resulted in the pattern of haemolysis seen, which has been reported previously. 

Mohamed M, Bates G, Eastley B. Massive intravascular haemolysis after high dose intravenous immunoglobulm therapy. Br J Haematol March 2013 160(5) 570. 

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