Experimental Transfusion Reactions in Monkeys: Haemolytic, Coagulant and Renal Effects of Transfused Isoimmune IgG and IgM

Lopas, Harry; Birndorf, N. I.; Bell, C. Elliott; Robboy, SJ; Fortwengler, H. Philip; Biddison, William E.

doi:10.1111/j.1365-2141.1972.tb03491.x

Cited by 7 publications

(8 citation statements)

References 21 publications

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“…Acute hemolytic episodes in both man and laboratory animals are often accompanied by coagulation changes ranging from mild hypercoagulability (13,14) to overt disseminated intravascular coagulation (4,15,16). DIC in humans has been associated with both immune (e.g., hemolytic transfusion reactions [1,4]) and nonimmune (e.g., falciparum malaria [5]) hemolysis, suggesting that hemolysis per se rather than the hemolytic agent is the critical Fro.…”

Section: Discussionmentioning

confidence: 99%

“…factor in DIC induction. Studies in laboratory animals have strongly supported these observations, especially with the development of a hemolytic transfusion reaction (HTR) model in the Cynomolgus monkey (Macaca irus) (2,16). Hemolytic antibody, prepared by immunization of donor monkeys with allogeneic RBC's, when infused into recipient monkeys as either whole plasma or the hemolytic IgG fraction, produces brisk hemolysis followed by laboratory and histopathologic evidence of DIC.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of the Alternate Complement Pathway by Autologous Red Cell Stroma

Poskitt

Fortwengler

Lunskis

1973

The Journal of Experimental Medicine

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The syndrome of disseminated intravascular coagulation (DIC) 1 is a recognized complication of acute hemolytic episodes in both man (1-3) and laboratory animals (4, 5) and has been induced experimentally in monkeys and dogs by infusion of autologous red blood cell stroma (6, 7). The mechanism of stromainduced D I C may be analogous to the demonstrable procoagulant activity of red cell membrane phospholipids in vitro. However, an additional or alternative chain of events involving activation of the complement system is suggested by the well-studied model of DIC, the Sanarelli-Shwartzman reaction, produced by two appropriately spaced intravenous injections of bacterial endotoxin. The recent work of Fong and Good (8) and Margaretten (9) indicate a requirement for platelets and an intact complement system for endotoxin-induced DIC. Complement activation by endotoxin proceeds primarily, if not entirely, via the recently described alternate pathway (10). In view of the ultrastructural similarity between endotoxin and red cell stroma (i.e., bilaminar membrane [11]) and their ability to produce DIC, we have initiated studies to determine whether red cell stroma is also capable of activating the alternate complement pathway and to attempt to relate this function to the sequence of events leading to DIC. Materials and MethodsPreparation of A utologous Red Cell 3troma.--Hemoglobin-free red cell stroma was prepared from five human volunteers by a modification of a previously described method (7). 50 ml of anticoagulated whole blood was collected from each donor. The red cells were washed three times in cold 0.850-/0 saline with aspiration of the buffy coat and upper 5% of red cells after each wash to minimize platelet and leukocyte contamination. Red cells were lysed by suspension in 50 volumes of 20 mosmol phosphate buffer with gentle swirling for 1 h. Ghosts were separated from supernatant hemoglobin by centrifugation at 7,000 X g for 60 rain, resuspended in 0.85% saline, and recentrifuged at 7,000 )< g for another 60 rain. The supernatant was aspirated, and cold 0.85% saline was added equal to the volume of ghosts. The suspension 1 Abbreviations used in this paper: C3A, C3-Activator; C3PA, C3-Preactivator; DIC, disseminated intravascular coagulation; HTR, hemolytic transfusion reaction; PF-3, platelet factor 3.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Activation of the Alternate Complement Pathway by Autologous Red Cell Stroma

Poskitt

Fortwengler

Lunskis

1973

The Journal of Experimental Medicine

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“…7,[37][38][39][40] However, these are not optimal for studying human HTRs due to their expense and the limited flexibility. Although mRBC blood group systems were described, 8 and although antibody-mediated clearance of transfused, incompatible mRBCs occurs, 9,10 these polymorphisms were not exploited to study HTRs.…”

Section: Discussionmentioning

confidence: 99%

Mouse models of IgG- and IgM-mediated hemolysis

Schirmer

Song

Baliff

et al. 2006

Blood

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Well-characterized mouse models of alloimmune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBCs) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). In this novel murine "blood group system," mRBCs from hGPA-Tg IntroductionHemolytic transfusion reactions (HTRs) are dangerous complications of blood transfusions. IgM-mediated HTRs (IgM-HTRs) occur acutely, are usually due to ABO incompatibility, typically cause intravascular hemolysis, and can lead to shock, renal failure, coagulopathy, and death. 1 Although infrequent, IgM-HTRs have a high mortality rate. IgG-mediated HTRs (IgG-HTRs) are more common, but usually less severe, than IgM-HTRs; they can occur acutely or be delayed, typically cause extravascular hemolysis, and occasionally result in renal failure, coagulopathy, and death. 2 Symptomatic immune-mediated red blood cell (RBC) destruction also occurs in autoimmune hemolytic anemia (AIHA), 3 blood group incompatible transplantation, 4 and immune thrombocytopenic purpura (ITP) treated with Rh-immune globulin. 5 Although various different modalities are used to treat HTRs, there is no definitive evidence regarding efficacy. Given the sporadic nature of HTRs, designing human trials to evaluate treatment options is difficult. Therefore, to study the mechanisms underlying HTRs, to evaluate the efficacy of existing treatments, and to develop new treatments, a relevant, inexpensive, and tractable animal model is required. 6 A mouse model would be ideal for this purpose, 7 given the abundance of reagents and relevant knockout (KO) and transgenic (Tg) animals. Although mouse blood group polymorphisms exist, 8 and transfused incompatible mouse RBC (mRBCs) are rapidly cleared, 9,10 no one has exploited these findings to develop a model of HTRs. The availability of a Tg mouse expressing human glycophorin A (hGPA; gene symbol designation, GYPA) on mRBCs 11 offers an approach using a well-described glycoprotein target and well-characterized reagents.We describe initial studies validating mouse models of IgG-and IgM-mediated alloimmune hemolysis. Thus, mRBCs from hGPA-Tg donors were transfused into non-Tg recipients that were passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). The clearance of the transfused mRBCs was quantified and the roles of complement and Fc␥ receptors were evaluated. Materials and methods AntibodiesPurified mAbs NaM10-2H12 (IgG3), NaM26-3F4 (IgG1), and NaM10-6G4 (IgG2a), which recognize peptide epitopes on the M and N forms of hGPA, 12 were purchased from EFS (Nantes, France). Hybridomas producing mAb 6A7, an IgG1 specific for a sialic acid-dependent epitope on M-type hGPA, 13-15 10F7, an IgG1 recognizing a nonpolymorphic epitope on hGPA, 13,14 and J11d, a rat IgM recognizing CD24 on mRBCs, 16,17...

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“…C mediated hemolysis in particular, and the various forms of shock in triggering intravascular coagulation are not clearly defined. Thus, intravascular hemolysis produces D1C [13,14]; however, the coagulation defect is absent in IgM anti body-induced lysis although other proper ties, such as platelet sequestration into the lungs may be seen [7]. Similarly, in septi cemia, both thrombocytopenia and 'septic shock' may occur without DIC [23], None theless.…”

Section: Discussionmentioning

confidence: 99%

“…Since acute hemolytic episodes are fre quently accompanied by coagulation changes ranging from mild 'hypercoagula bility' [1, 11| to overt intravascular coagu lation [13,14,18,20], and because activa tion of the ACP is associated with DIG [8. 12, 24], a scries of experiments was per formed to determine the effect of alien se rum injection on the clotting parameters of the recipients.…”

Section: Relationship Of Human Serum Injection To Other Hematologicalmentioning

confidence: 99%

Heterotoxicity of Human Serum V.

Rozenfarb

Eidinger

1979

Int Arch Allergy Immunol

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Intravenous injections of fresh human serum (FHS) with an operative alternative complement pathway (ACP) were toxic for mice. The toxic reaction was manifested by intravascular hemolysis, hemoglobinuria, and a slight prolongation in the mean activated thromboplastin time, prothrombin time and thrombin time. In moribund animals, this was followed by a profound thrombocytopenia and alterations in the leukocyte counts. Marked to slight leukopenia developed in animals dying relatively quickly, while leukocytosis was observed infrequently in animals dying after a protracted shock, and only in concurrence with hemoconcentration and thrombocytopenia. Although the latter sequence of events was not investigated extensively, it may have led to intravascular coagulation. During the acute phase of the reactions, the deposition of platelets mainly in the lungs, and erythrocytes mainly in the liver, was demonstrated by accumulation of radioactive labelling of platelets and erythrocytes, respectively. Histologic sections of the lung revealed hemorrhagic lesions and the accumulation of ‘platelet-like’ thrombi in the pulmonary vessels. The blood films of animals injected with active serum showed erythrocytes ghosts, but no hemagglutination or distinctive microangiopathic changes. The fatal consequence of serum injections could not be prevented by the administration of cortisone, histamine and serotonin antagonists, anticoagulants, or by β-adrenergic blockade. The injections of homologous erythrocytes lysed by human serum, but not of sonicated red cell, produced histopathologic lesions suggestive of disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenic purpura (TTP) in the lungs. It is suggested that the interaction of complement and the coagulation system might induce the development of syndromes characterized by DIC or TTP, or thrombotic phenomena in other conditions.

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Experimental Transfusion Reactions in Monkeys: Haemolytic, Coagulant and Renal Effects of Transfused Isoimmune IgG and IgM

Cited by 7 publications

References 21 publications

Activation of the Alternate Complement Pathway by Autologous Red Cell Stroma

Activation of the Alternate Complement Pathway by Autologous Red Cell Stroma

Mouse models of IgG- and IgM-mediated hemolysis

Heterotoxicity of Human Serum V.

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