Prevention of adverse reactions to dextran Karl-Gösta Ljungström M.D., Ph.D., Associate professor,...
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Transcript of Prevention of adverse reactions to dextran Karl-Gösta Ljungström M.D., Ph.D., Associate professor,...
Prevention of adverse reactions to dextran
Karl-Gösta Ljungström M.D., Ph.D., Associate professor,
Karolinska Institute Department of Surgery Danderyd Hospital Stockholm Sweden
Dextran
In clinical use since 1947.
Manufacturing process:
Sucrose is converted by Leuconostoc mesenteroides to native dextran, which is hydrolysed and fractionated. Since 1955 the B512 strain of Leuconostoc is used, producing a dextran molecule with few sidebranches
Dextran - >50 years in clinical use
Replacement of blood loss
Plasma replacement
Thrombosis prophylaxis
Volume expansion
Rheological improvement Optic medium in surgery
Pharmacological agent
Adverse effects of colloids
Fluid overload
Renal function impairment
Dilution of coagulation factors
Loading of the RES and storage in the body
Allergic reactions
Anaphylactoid or anaphylactic reactions to colloids?
Anaphylactoid - an adverse reaction with allergic symptoms but NOT
involving preformed antibodies. The mechanisms involved may be quite different in seemingly similar reactions.
Anaphylactic-an allergic reaction involving either reaginic
antibodies (IgE), e.g. some reactions to gelatin, or antibodies of other classes (IgG, IgM, IgA), e.g. dextran reactions.
Allergic reactions to dextran
DIAR =
Dextran induced anaphylactoid/anaphylactic reactions
DRA =Dextran reactive antibodies
DIAR have dual pathomechanisms
Mild dextran reactions are anaphylactoid and many of these patients have a history of allergy.
Severe DIAR are anaphylactic and are caused by preformed DRA, predominantly of IgG-class, causing a type III or immune complex anaphylaxis. Elevated IgE-levels and histamine liberation has not been found in DIAR
Pathomechanism for severe DIAR
DRA + Clinical dextran
Immune complexes
Activation of vasoactive
platelets mediators causing leucocytes flush, shock,
complement bronchospasm coagulation etc
Classification of DIARGrade of Characteristic symptoms severity
I Skin manifestations(flush, erythema, urticaria) Lumbar pain
II Mild to moderate hypotension Gastrointestinal disturbances Respiratory distress III Severe hypotension, shock Bronchospasm IV Cardiac and/or respiratory arrestV Fatal reaction
Potential antigenic stimuli for DRA production
Native dextran
Dental plaques
Food additive
Contaminant of sucrose
Cross-reactive polysaccharides
Pneumococci
Streptococci
Salmonella
Klebsiella
Hapten
An incomplete antigen, unable to induce the formation of antibodies but still able to bind to specific antibodies
The name (from greek hapto = to seize) was introduced by Karl Landsteiner 1921
Scandinavian studies with dextran 1, 1978-1982
N. pat N. severe DIAR
1.5 g dx 1 preinj. 29 252 7
p=0,010
3 g dx 1 preinj. 41 099 1
(combined)
DIAR in Sweden before and after introduction of Promit®
DIAR, grades of severity I II III IV V Total 1975- Without 1979 dextran 1 61 94 78 44 23 300 (0.3 milj. patients) 145 (1/2 000 patients)
1983- With 1992 dextran 1 78 44 12 4 1 139 (1.2 milj. patients)
17 (1/70 000
patients)
Reactions to dextran 1
Type Symptoms No.A Skin symptoms (flush, 22
erythema, urticaria)B Bradycardia ± hypotension 6C Hypotension 10Misc. Dizziness, nausea etc 8
Total 46Incidence: 1 in 100 000 doses
DIAR in Sweden 1993-2004
DIAR, grades of severity I II III IV V Total 1975- Without 1979 dextran 1 61 94 78 44 23 300 (0.3 mil. patients) 145 (1/2 000 patients)
1993- With 2004 dextran 1 18 26 13 2 0 62 (≈1 mil. patients)
15 (1/67 000
patients)
DRA-titers in some examples of mitigated severe DIAR
Reg.no. Grade DRA-titer
86-P-Mac-27 II 2 000 000
88-P-Mac- 1 III 32 768
91-P-Mac-2 III 33 000 000
92 30315 III 134 000 000
References
Hedin H, Richter W: Pathomechanisms of dextran-induced anaphylactoid/anaphylactic reactions in man. Int Arch Allergy Appl Immunol 1982; 68: 122-6. Ljungström K-G. Safety of dextran in relation to other colloids - Ten years experience with hapten inhibition. Infusionsther Transfusionsmed 1993; 20: 206-10.Ljungström K-G. Colloid safety - fact or fiction. In: Baillière’s Clinical Anaesthesiology, 1997, vol.11: 163-177.