Fortschr. Röntgenstr. 125, 3
Waldenströms MakroGlobulinamie und intravenose Kontrastmittel
Fortschr. Röntgenstr. 125, 3 (1976) 262-263 © Georg Thieme Verlag, Stuttgart
Waldcnströms macroglobulinaemia and intravenous contrast media By D. Catalano, A. Valente and G. Fucci Radiological Department Ospedali Ascalesi-S. Gennaro - Naples, Italy
In vivo and in vitro studies have been performed in a group of patients with immunoproliferative diseases to evaluate the risk of serious reactions due to serum jelling after intravenous injection of iodinated contrast media. Sol-jeu convertion and/or turbidimetric variations have not been observed when either sera or plasmas have been mixed with variable amounts of a methylglucamine salt of ioglycamic acid (MGI) and other compounds. In addition, no side-effects have been clinically recorded in three patients with Waldenströms macroglobulinaemia (WM) whose sera and/or plasmas had been studied in vitro, when they habe been submitted to intravenous contrast examinations. The results suggest that there is not an evidence of a relationship between iodinated contrast media and fatal reactions due to sol-jell alterations in patients with WM and therefore a radiological examination using contrast media may be carried out in those patients. Bauer and Co-workers have reported the sudden death of a patient with Waldenström's macroglobulinaemia (WM) after intravenous injection of a methylgiucamine salt of ioglycamic acid (MGI) used for intravenous cholangiography. Postmortem examination revealed multiple thrombotic vascular occlusions, due to erythrocytic aggregates, in the peripheral venous blood. When detailed in vitro studies were undertaken, a sudden jelling was found to occur upon the addition of such compound to the patient's serum, even with a concentration as low as 1 r1/ml of serum. This sol-jell conversion
appeared to be independent of the variations of either temperature or pH, although a slight jelling increase was observed at pH ranging between 4,5 and 5,5. Similar results
were obtained by the same authors with two additional macrogloboulinaemic sera, suggesting a high risk of fatal reactions when intravenous contrast examinations are performed in WM. On the other hand, negative results were obtained with a number of closely related contrast media, except for a methyiglucamine iodipamide, that gave only in one patient a slight serum precipitation.
The current study was undertaken to investigate the risk of serum jelling by intravenous contrast media may be considered as high in WM as it emerges throughout the Bauer and Co-workers paper.
In einer Reihe von Patienten mit immun-proliferierenden Erkrankungen wurden Untersuchungen in vivo und in Vitro vorgenommen um das Risiko schwerer, Reaktionen auf Serum-jelling nach intravenöser Injektion jodenthaltender Kontrastmittel auszuwerten. Sol-,,jell" Wandlung und/oder turbidimetrische Variablen wurden nicht beobachtet, wenn entweder Sera oder Plasma mit verschiedenen Mengen von Methylgiukaminsaizen von Jodglykamisäure (MGI) und anderen Verbindungen gemischt wurde. Ferner haben wir keine klinischen Nebenwirkungen bei 3 Patienten mit Waldenströms Makro-Globulinämie (WM) beobachtet, deren Sera und/oder Plasma in vitro untersucht wurden, wenn Untersuchungen mit intravenösen Kontrastmitteln an ihnen vorgenommen wurden. Die Ergebnisse legen es nahe, daß es keine Anhaltspunkte dafür gibt, daß ein Zusammenhang zwischen jodenthaltenden Kontrastmitteln und tödlichen Reaktionen aufgrund von Veränderungen von Sol-,,jell" bei Patienten mit WM besteht. Röntgenuntersuchungen mit Kontrastmitteln können daher bei solchen Patienten ausgeführt werden. (F. St.)
Material and methods 10 cases of WM, 12 of IgG-myelomatosis and 20 of IgG1gM mixed cryoglobulinaemia were included in this study.
Except for 4 WM cases that were only avaible as ACDplasmas obtained by plasmapheresis, trials of jelling were performed on both sera and heparinized plasmas. 1 ml of serum and/or plasma was mixed at room temperature with a 17% acqueous solution of MGI, 1 and S ii. Changes of the sol-je!! state were investigated immediately and after S min. from the addition of this medium. Optical densities
were a!so recorded in a turbidimeter at 610 nm and after S min. from the mixture formation. The influence of temperature on serum so!-je!! conversion was investigated in a turbidimetric apparatus at 610 nm by mixing S t! of MGI with the serum semples adjusted at
pH 5,5 with 0,1 N HC1 and keeping then at + 4 C° and + 37 C° for 60 min. To test whether other intravenous contrast media different from MGI were capable of serum jelling in WM and in allied disorders, 0,5 m! of serum samples were mixed with S tl of the fo!!owing compounds: SOS/o acqueous solution of methyl-
glucamine iodipamide and 40,3% acqueous solution of a
Further experiments were performed to assess whether serum
methylg!ucamine salt of iodoxamic acid. Further, investigations were performed on both electrophoretic and analytical
jelling may occur in other immunoproliferative diseases, such as multiple myeloma and essential cryoglobulinaemia.
ultracentrifugation patterns of the WM homogeneous Mspikes upon contact with MGI.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
262
Fortschr. Röntgenstr. 125, 3
Waldenströms macroglobulinaemia and intravenous contrast media
263
Table 1. In Vitro experiments of serum sol-jeu conversion in lo patients with Waldenström's macroglobulinaemia upon addition of a methylgiucamine salt of ioglycamic acid (MGI). Patients
Sex, age
Total protein gr per 100 ml
M-spike gr per 100 ml
Cryoglobulins
Turbidimetric variations
Sol-jeu conversion with 1 and S u! of MGI per ml at room at temperatures temperature ranging between
at pH 5,5
+4G° and +37G°
A. T.
M 55
C.C.
M53 F67 F50 M43 F63
B.S.
G.E.
V.P. M.N.
SN.
8,1
9,2 8,4 6,8 9,1 8,4
7,8 8,0 7,9 8,8
3,8 2,1 2,4 3,5 4,0 3,8 3,7 4,2 3,9 5,4
+ +
+ +
Electropherograms (cellulose acetate, pH 8,6) of 6 out lo sera
the same experimental condizions. Negative results were
were compared by scanning with those obtained after the
equally obtained with contrast media closely related to MGI.
addition of MGI, S ii/ml. Ultracentrifugation was performed
On the other hand, variations in either electrophoretic or ultracentrifugation patterns were consistently absent after mixing sera with MGI. Similarly, a chromatografically
in a Beckman Spinco Model E ultracentrifuge at 59.000 rev/mm. The ultracentrifugation patterns of 3 out 10 sera, mixed with MGI, S ii/mi, were compared with those obtained
by the same sera without addition of the contrast medium. The M-component of patient P. G. with WM was isolated by gel filtration chromatography on a Sephadex G-200 column, equilibrated with 0,2 M-sodium acetate buffer, pH 4,0. The purity of this fraction was assessed by immunoelectrophoresis
and ultracentrifugation. Trials of jelling were performed on this isolated M-component, resuspended in buffered saline at concentrations rancing between 20 and 40 mg/mi, and then additioned with MGI, 5 ii/ml. In order to test whether reactions may follow intravenous contrast examinations when previous in vitro experiments have excluded any sol-jell conversion by contrast media. two patients with WM were submitted to an intravenous cholangiography with MGI, while in another patient with WM an intravenous pyelography was performed using a 30% acqueous solution of a methylglucamine salt of diatri-
zoic acid. Obviously, the patients were closely followed during the contrast medium injection and throughout the entire radiological examination and, in addition, a number of
clinical and laboratory data (EGG, BUN, fasting blood sugar, electrolytes, serum calcium concentration) were per-
formed at the end of the contrast injection and compared with the corresponding admission values.
Results As shown in the table, no sol-jeu conversion was observed at
room temperature when sera and/or heparinized plasmas were mixed with MGI, even when 5 ii of this medium was added. Further, no turbidimetric variations were recorded. The same results were observed on pH 5,5-adjusted sera at + 4 G° and + 37 C°. Moreover, neither sol-jeu conversion nor turbidimetric variations were observed in cases of multiple myeloma and mixed cryoglobulinaemia examined in
purified Waldenström's type M component did not jell upon contact with this medium. When in vitro serum jellung has been ruled out, no reactions of any kind were recorded in WM patients submitted to intravenous contrast examinations and no clinical or laboratory changes were observed in those patients.
Discussion and conclusion Our experimental studies did not confirm Bauer and Coworkers' observations. As a matter of fact Mathieu and Brauman, applying the same experimental conditions, did not
observe in vitro any increase of viscosity or jelification in three cases of WM using Biligram (MGI) as contrast medium. It is not possible to explain the results referred by Bauer and
Go-workers and the sudden death of their patient. There must be other unknown factors responsible of this event than those related to serum jelling.
The laboratory findings obtained by us and confirmed by those of Mathieu and Brauman and the absence of untoward
reactions after intravenous injection of contrast media in the three patients with WM seem, suggest that there is not any possible relationship between WM and contrast media. Therefore a radiological examination using iodinadet contrast media may be performed in patients with WM. Literatur Bauer, K., E. H. Tragl, G. W. Bauer, W. Vyensilik, P. Hocher: Intravasale Denaturierung von Plasmaproteinen bei einer IgM-Paraproteinämie, ausgelöst durch intravenös verabreichtes
Röntgenkontrastmittel. Wien. med. Wschr. 44 (1974) 766
lebergängiges
Mathieu, J., J. Brauman: Absence de reaction in vitro entre 2.4.6-triiodo-3carboxanilide (Biligram) et paraproreine 1gM. J. belge Radiol. 58 (1975) 95
Prof. D. Gatalano, Via Gostantinopoli, 84, 80138-Naples, Italy
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
P.G.
F56 F64 M61 M59
D.A. A.G.
Waldenströms MakroGlobulinamie und intravenose Kontrastmittel
Fortschr. Röntgenstr. 125, 3 (1976) 262-263 © Georg Thieme Verlag, Stuttgart
Waldcnströms macroglobulinaemia and intravenous contrast media By D. Catalano, A. Valente and G. Fucci Radiological Department Ospedali Ascalesi-S. Gennaro - Naples, Italy
In vivo and in vitro studies have been performed in a group of patients with immunoproliferative diseases to evaluate the risk of serious reactions due to serum jelling after intravenous injection of iodinated contrast media. Sol-jeu convertion and/or turbidimetric variations have not been observed when either sera or plasmas have been mixed with variable amounts of a methylglucamine salt of ioglycamic acid (MGI) and other compounds. In addition, no side-effects have been clinically recorded in three patients with Waldenströms macroglobulinaemia (WM) whose sera and/or plasmas had been studied in vitro, when they habe been submitted to intravenous contrast examinations. The results suggest that there is not an evidence of a relationship between iodinated contrast media and fatal reactions due to sol-jell alterations in patients with WM and therefore a radiological examination using contrast media may be carried out in those patients. Bauer and Co-workers have reported the sudden death of a patient with Waldenström's macroglobulinaemia (WM) after intravenous injection of a methylgiucamine salt of ioglycamic acid (MGI) used for intravenous cholangiography. Postmortem examination revealed multiple thrombotic vascular occlusions, due to erythrocytic aggregates, in the peripheral venous blood. When detailed in vitro studies were undertaken, a sudden jelling was found to occur upon the addition of such compound to the patient's serum, even with a concentration as low as 1 r1/ml of serum. This sol-jell conversion
appeared to be independent of the variations of either temperature or pH, although a slight jelling increase was observed at pH ranging between 4,5 and 5,5. Similar results
were obtained by the same authors with two additional macrogloboulinaemic sera, suggesting a high risk of fatal reactions when intravenous contrast examinations are performed in WM. On the other hand, negative results were obtained with a number of closely related contrast media, except for a methyiglucamine iodipamide, that gave only in one patient a slight serum precipitation.
The current study was undertaken to investigate the risk of serum jelling by intravenous contrast media may be considered as high in WM as it emerges throughout the Bauer and Co-workers paper.
In einer Reihe von Patienten mit immun-proliferierenden Erkrankungen wurden Untersuchungen in vivo und in Vitro vorgenommen um das Risiko schwerer, Reaktionen auf Serum-jelling nach intravenöser Injektion jodenthaltender Kontrastmittel auszuwerten. Sol-,,jell" Wandlung und/oder turbidimetrische Variablen wurden nicht beobachtet, wenn entweder Sera oder Plasma mit verschiedenen Mengen von Methylgiukaminsaizen von Jodglykamisäure (MGI) und anderen Verbindungen gemischt wurde. Ferner haben wir keine klinischen Nebenwirkungen bei 3 Patienten mit Waldenströms Makro-Globulinämie (WM) beobachtet, deren Sera und/oder Plasma in vitro untersucht wurden, wenn Untersuchungen mit intravenösen Kontrastmitteln an ihnen vorgenommen wurden. Die Ergebnisse legen es nahe, daß es keine Anhaltspunkte dafür gibt, daß ein Zusammenhang zwischen jodenthaltenden Kontrastmitteln und tödlichen Reaktionen aufgrund von Veränderungen von Sol-,,jell" bei Patienten mit WM besteht. Röntgenuntersuchungen mit Kontrastmitteln können daher bei solchen Patienten ausgeführt werden. (F. St.)
Material and methods 10 cases of WM, 12 of IgG-myelomatosis and 20 of IgG1gM mixed cryoglobulinaemia were included in this study.
Except for 4 WM cases that were only avaible as ACDplasmas obtained by plasmapheresis, trials of jelling were performed on both sera and heparinized plasmas. 1 ml of serum and/or plasma was mixed at room temperature with a 17% acqueous solution of MGI, 1 and S ii. Changes of the sol-je!! state were investigated immediately and after S min. from the addition of this medium. Optical densities
were a!so recorded in a turbidimeter at 610 nm and after S min. from the mixture formation. The influence of temperature on serum so!-je!! conversion was investigated in a turbidimetric apparatus at 610 nm by mixing S t! of MGI with the serum semples adjusted at
pH 5,5 with 0,1 N HC1 and keeping then at + 4 C° and + 37 C° for 60 min. To test whether other intravenous contrast media different from MGI were capable of serum jelling in WM and in allied disorders, 0,5 m! of serum samples were mixed with S tl of the fo!!owing compounds: SOS/o acqueous solution of methyl-
glucamine iodipamide and 40,3% acqueous solution of a
Further experiments were performed to assess whether serum
methylg!ucamine salt of iodoxamic acid. Further, investigations were performed on both electrophoretic and analytical
jelling may occur in other immunoproliferative diseases, such as multiple myeloma and essential cryoglobulinaemia.
ultracentrifugation patterns of the WM homogeneous Mspikes upon contact with MGI.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
262
Fortschr. Röntgenstr. 125, 3
Waldenströms macroglobulinaemia and intravenous contrast media
263
Table 1. In Vitro experiments of serum sol-jeu conversion in lo patients with Waldenström's macroglobulinaemia upon addition of a methylgiucamine salt of ioglycamic acid (MGI). Patients
Sex, age
Total protein gr per 100 ml
M-spike gr per 100 ml
Cryoglobulins
Turbidimetric variations
Sol-jeu conversion with 1 and S u! of MGI per ml at room at temperatures temperature ranging between
at pH 5,5
+4G° and +37G°
A. T.
M 55
C.C.
M53 F67 F50 M43 F63
B.S.
G.E.
V.P. M.N.
SN.
8,1
9,2 8,4 6,8 9,1 8,4
7,8 8,0 7,9 8,8
3,8 2,1 2,4 3,5 4,0 3,8 3,7 4,2 3,9 5,4
+ +
+ +
Electropherograms (cellulose acetate, pH 8,6) of 6 out lo sera
the same experimental condizions. Negative results were
were compared by scanning with those obtained after the
equally obtained with contrast media closely related to MGI.
addition of MGI, S ii/ml. Ultracentrifugation was performed
On the other hand, variations in either electrophoretic or ultracentrifugation patterns were consistently absent after mixing sera with MGI. Similarly, a chromatografically
in a Beckman Spinco Model E ultracentrifuge at 59.000 rev/mm. The ultracentrifugation patterns of 3 out 10 sera, mixed with MGI, S ii/mi, were compared with those obtained
by the same sera without addition of the contrast medium. The M-component of patient P. G. with WM was isolated by gel filtration chromatography on a Sephadex G-200 column, equilibrated with 0,2 M-sodium acetate buffer, pH 4,0. The purity of this fraction was assessed by immunoelectrophoresis
and ultracentrifugation. Trials of jelling were performed on this isolated M-component, resuspended in buffered saline at concentrations rancing between 20 and 40 mg/mi, and then additioned with MGI, 5 ii/ml. In order to test whether reactions may follow intravenous contrast examinations when previous in vitro experiments have excluded any sol-jell conversion by contrast media. two patients with WM were submitted to an intravenous cholangiography with MGI, while in another patient with WM an intravenous pyelography was performed using a 30% acqueous solution of a methylglucamine salt of diatri-
zoic acid. Obviously, the patients were closely followed during the contrast medium injection and throughout the entire radiological examination and, in addition, a number of
clinical and laboratory data (EGG, BUN, fasting blood sugar, electrolytes, serum calcium concentration) were per-
formed at the end of the contrast injection and compared with the corresponding admission values.
Results As shown in the table, no sol-jeu conversion was observed at
room temperature when sera and/or heparinized plasmas were mixed with MGI, even when 5 ii of this medium was added. Further, no turbidimetric variations were recorded. The same results were observed on pH 5,5-adjusted sera at + 4 G° and + 37 C°. Moreover, neither sol-jeu conversion nor turbidimetric variations were observed in cases of multiple myeloma and mixed cryoglobulinaemia examined in
purified Waldenström's type M component did not jell upon contact with this medium. When in vitro serum jellung has been ruled out, no reactions of any kind were recorded in WM patients submitted to intravenous contrast examinations and no clinical or laboratory changes were observed in those patients.
Discussion and conclusion Our experimental studies did not confirm Bauer and Coworkers' observations. As a matter of fact Mathieu and Brauman, applying the same experimental conditions, did not
observe in vitro any increase of viscosity or jelification in three cases of WM using Biligram (MGI) as contrast medium. It is not possible to explain the results referred by Bauer and
Go-workers and the sudden death of their patient. There must be other unknown factors responsible of this event than those related to serum jelling.
The laboratory findings obtained by us and confirmed by those of Mathieu and Brauman and the absence of untoward
reactions after intravenous injection of contrast media in the three patients with WM seem, suggest that there is not any possible relationship between WM and contrast media. Therefore a radiological examination using iodinadet contrast media may be performed in patients with WM. Literatur Bauer, K., E. H. Tragl, G. W. Bauer, W. Vyensilik, P. Hocher: Intravasale Denaturierung von Plasmaproteinen bei einer IgM-Paraproteinämie, ausgelöst durch intravenös verabreichtes
Röntgenkontrastmittel. Wien. med. Wschr. 44 (1974) 766
lebergängiges
Mathieu, J., J. Brauman: Absence de reaction in vitro entre 2.4.6-triiodo-3carboxanilide (Biligram) et paraproreine 1gM. J. belge Radiol. 58 (1975) 95
Prof. D. Gatalano, Via Gostantinopoli, 84, 80138-Naples, Italy
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
P.G.
F56 F64 M61 M59
D.A. A.G.
