Hematologic disorders caused

This category includes patients with rare causes of strokes such as nonatherosclero-tic vasculopathies, cerebral venous thrombosis, hypercoagulable states, or hematologic disorders. Two such disorders are discussed below. 

Alcohol indirectly affects hematopoiesis through metabolic and nutritional effects and may also directly inhibit the proliferation of all cellular elements in bone marrow. The most common hematologic disorder seen in chronic drinkers is mild anemia resulting from alcohol-related folic acid deficiency. Iron deficiency anemia may result from gastrointestinal bleeding. Alcohol has also been implicated as a cause of several hemolytic syndromes, some of which are associated with hyperlipidemia and severe liver disease. 

Adverse Effects. The most serious problems associated with ganciclovir include anemia, granulocytopenia, thrombocytopenia, and related hematologic disorders. Ganciclovir may also cause gastrointestinal disturbances (nausea, loss of appetite) and CNS disturbances (mood changes, nervousness, tremor). 

In addition to the risk of bleeding, which will be detailed in the different studies, thienopyridines are able to cause skin disorders (rashes or prurit) and gastrointestinal disorders (diarrhea). In the CLASSICS study, these side effects were observed in 8.2% of patients treated with ticlopidine and in 3.5% of those taking clopidogrel treatment. The most serious problem was related to hematologic disorders neutropenia or thrombocytopenia. These disorders are much less frequent with clopidogrel than with ticlopidine 0.04% of neutropenia in the CAPRIE study and 0.05% in the CURE trial, Thrombotic thrombocytopenic purpura are exceptional one for 200,000 patients. 

Other causes of gastric atrophy, such as those due to Helicobacter pylori,AIDS, or radiation injury, can lead to a similar outcome but from different pathogenic mechanisms. Therefore, vitamin B12 deficiency, resulting in neurological, psychiatric, metabolic, and hematological disorders, can arise from any one of the many causes listed in Table 28-1. For this reason, the term pernicious anemia (PA) is used here to describe only the classical disease that is associated with IF deficiency due to autoimmune gastritis. 

A number of hematological disorders may occasionally cause ischemic stroke and TIA (Tatlisumak and Fisher 1996 Arbors and Besses 1997 Markus and Hambley 1998 Matijevic and Wu 2006) (Box 6.2). 

Hexachlorobenzene (a fungicide) has caused porphyria cutanea tarda in humans. It does not cause convulsions. Lindane, chlordane, and dieldrin have been associated anecdotally with certain rare hematologic disorders, including aplastic anemia the incidence of these effects appears to be extremely low. 

One of the rare studies of the excretion of tryptophan metabolites, both spontaneous and after load, by patients with hematological disorders, is the work of Altman and Miller (A4). They reported an elevated urinary excretion of anthranilic acid in 9 children with an unusual congenital anemia referred to as erythrogenesis imperfecta (A4). Oral administration of 1.6 g L-tryptophan to one patient led to increased urinary excretion of anthranilic acid as well as other intermediary metabolites of tryptophan. Massive doses of riboflavin per os during 30 days caused no change in the hematological status, but there appeared to be a decrease in the amount of anthranilic acid excreted. 

Interferon alfa has direct myelosuppressive effects and can also cause hematological disorders by immune blood cell destruction, as suggested by reports of immune-mediated thrombocytopenia, immune hemolytic anemia (205,206), or a positive direct Coombs test, with or without hemolysis (207-209). 

NSAIDs have been reported to cause potentially severe hematological disorders thrombocjdopenia, agranulocytosis, aplastic anemia, and hemolytic anemia (50). Thrombocytopenia is generally mild and reversible and has a low case-fatahty rate, but deaths from bleeding have been reported, particularly with indometacin, oxjrphen-butazone, and phenylbutazone (50). 

Some drugs and ingested toxins such as nitrofurantoin, cancer chemotherapy agents, phenazopyridine, sulfones, amyl nitrate, mothballs, paraquat, and hydrogen peroxide can cause direct oxidative damage to erythrocytes (see Chap. 102 on drug-induced hematologic disorders). 

Drug-induced hematologic disorders can affect any ceU line, including white blood cells (WBCs), red blood cells (RBCs), and platelets. When a drug causes decreases in all three cell fines accompanied by a hypoplastic bone marrow, the result is drug-induced... 

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