Dextran anaphylactoid reactions

HT is relatively more potent than histamine in increasing vascular permeability in the rat [61, 137, 414, 485, 487, 534, 578, 581]. Parratt and West [482-490] extensively studied the significance of the presence of the substantial amounts of both 5-HT and histamine in the skin and subcutaneous tissues of the rat, and the importance of their release from these sites during the anaphylactoid reaction. Polymyxin B sulphate released more than 90% of the histamine in the rat skin but less than 20% of its 5-HT on the other hand, reserpine released more than 90% of the 5-HT but only small amounts of the histamine. Pretreatment with reserpine, but not with polymyxin B sulphate, effectively inhibited both the egg-white and dextran anaphylactoid reaction. Further evidence for an important role of 5-HT in the anaphylactoid reaction was obtained when it was found that after an intraperitoneal injection of egg-white or dextran 5-HT, but not histamine, was present in the oedema fluid associated with the subcutaneous tissues on the dorsal side of the foot. 

V.W.Adamkiewicz, R.J.Fitko and A.A.Fortier, Hypoglycemic Drugs and the Dextran Anaphylactoid Inflammation, Can. J. Biochem. Physiol. 38, 823-827 (1960). V.W.Adamkiewicz and Y.Langlois, Sensitization by Insulin to the Dextran Anaphylactoid reaction. Can. J. Biochem. Physiol. 35, 251-256 (1957). 

A. Redei, S. Nagy and S. Karady, Insulin and the Dextran Anaphylactoid Reaction, Naturwissenschaften 48, 380-381 (1961). 

Adverse effects of colloids are generally extensions of their pharmacologic activity (e.g., fluid overload, dilutional coagulopathy). Albumin and dex-tran may be associated with anaphylactoid reactions or anaphylaxis. Bleeding may occur in certain patients receiving hetastarch and dextran. 

Different allergic results have also been observed in rats and man, when linear and branched dextrans are compared. The relative activities of the two kinds of dextran can be reversed when two different, allergic phenomena are studied, such as an anaphylactoid reaction following parenteral injection, and wheal and erythema production following injection into the skin. Presumably, the relative importance of terminal and nonterminal specificities is also involved in these phenomena.146... 

The most important adverse effect results from the antigenicity of dextrans, which may lead to an anaphylactoid reaction. Dextran antibodies can be intercepted without an immune response by injection of small dextran molecules (MW 1000), thus obviating any incompatibility reaction to subsequent infusion of the dextran plasma substitute solution. 

Adverse ejfects include anaphylactoid reactions dextran and hetastarch can impair haemostatic mechanisms. 

Non-IgE-mediated anaphylactic (anaphylactoid) reactions suspected to be caused by dextran as used in BCG vaccines have been described (SEDA-16, 375). 

The incidence of anaphylactoid reactions to dextran was studied in 5745 patients over 63 months from January 1981 to March 1986 (27). A total of 12 646 half-liter units of dextran 70 had been administered to these patients. The average number of dextran units transfused was 2.2 per patient. There were 15 reactions, a rate of one reaction per 383 patients treated (0.26%). Seven of these reactions were potentially life-threatening (grade III or IV), giving a combined incidence of severe reactions of one in 821 patients treated (0.12%). The remaining eight reactions were less severe (grade I or II), and the combined incidence of the milder reactions was 1 718 patients treated (0.14%). 

It is possible for a severe dextran-induced anaphylactic/ anaphylactoid reaction to develop despite prophylaxis with monovalent hapten dextran (30). This has been reported in a 60-year-old patient with multiple trauma, who received a dextran infusion for prophylaxis of thrombosis due to severe thrombocjdosis in the late postoperative period. The causal relation to dextran was considered likely, although no serum sample was taken before the reaction, due to the close time relation to the infusion of dextran 60. In addition, there were high titers of dex-tran-reactive antibodies in the blood drawn immediately after the reaction occurred. 

An anaphylactoid reaction in a pregnant woman occurred immediately after the administration of dextran 40 solution (32). The baby was delivered rapidly by cesarean section after the event, and was apparently dead at birth but successfully resuscitated. The case has prompted Barbier and colleagues to report on the safety in general of dextran administered during pregnancy (32). They found information on 32 moderate anaphylactoid reactions associated with severe fetal distress and they advised avoiding preventive fluid preload with dextran in pregnancy. 

Pauli J. A prospective study of dextran-induced anaphylactoid reactions in 5745 patients. Anaesth Intensive Care 1987 15(2) 163-7. 

Altman LC, Petersen PE. Successful prevention of an anaphylactoid reaction to iron dextran. Ann Intern Med 1988 109(4) 346-7. 

Keller C, Griitzmacher P, Bahr F, Schwarzbeck A, Kroon AA, Kiral A. LDL-apheresis with dextran sulphate and anaphylactoid reactions to ACE inhibitors. Lancet (1993) 341,60-1. 

Furhoff AK (1977) Anaphylactoid reaction to dextran. A report of 133 cases. Acta Anaes-thesiol Scand 21 161... 

Intracutaneous skin tests with 0.05 ml Macrodex were performed in 37 patients, who had experienced anaphylactoid reactions to dextran (Hedin et al. 1976). The incidence of positive wheal and flare responses was 11 % at 0-7 days, and 32% at 1-12 months after the reaction. In normal human subjects, positive skin tests with clinical dextran have been reported in 6%-19% (Bryan and Scudder 1952 Meissner 1961). From these findings it is concluded that skin tests are of limited value for prediction of anaphylactoid dextran reactions. 

Fig. 3. Relation between titers of hemagglutinating dextran-reactive antibodies (DRA) in sera of dextran reactors ( = 61) and severity of dextran-induced anaphylactoid reactions (DIAR). Titers were estimated on sera obtained prior to the reaction. (Hedin et al. 1981 a)...

The pathomechanism of HES-induced anaphylactoid reactions is unknown. Since HES has been in general clinical use for a comparatively short time, only a few data are available for critical evaluation of the triggering mechanisms of adverse reactions. From the physicochemical properties of HES a few possible mechanisms may, however, be visualized. Comparing the occurrence in humans of preformed antibodies reactive with plasma substitutes, it is evident that both titers and frequency are highest for gelatin, intermediate for dextran, and lowest for HES. In this connection, it is interesting to note that upon rapid infusion of HES into hu-... 

Bauer A, Ostling G (1970) Dextran-induced anaphylactoid reactions in connection with surgery. Acta Anaesthesiol Scand [Suppl] 37 182-185 Bauer K (1974) A study on the determinant structure of human serum albumin. J Immuno-genet 1 315-321... 

Brisman R, Parks LC, Haller JA (1968) Anaphylactoid reactions associated with the clinical use of dextran 70. JAMA 204 82 825... 

Johnson U, Laurell AB (1974) Activation of complement in anaphylactoid reactions in connection with infusion of dextran. Scand J Immunol 3 673-676 Kaars-Sijpesteijn JA, Huizinga T (1975) Blood and blood products. In Meyler s side effects of drugs, 8. Excerpta Medica, Amsterdam London New York, pp 721-737 Kabat EA (1957) Size and heterogeneity of the combining sites on an antibody molecule. J Cell Comp Physiol 50 79-102... 

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