Evaluation of Patients at Risk for Protamine Reactions

Levy, Jerrold H.; Schwieger, Ian M.; Zaidan, James R.; Faraj, Bahjat A.; Weintraub, William S.

doi:10.1097/00132586-199006000-00022

Cited by 22 publications

(29 citation statements)

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“…The diagnostic potential of rCyp c 1.01 was further investigated by basophil degranulation assay, which closely reflects allergic effector cell activation with the result that rCyp c 1.01 induced specific and dose-dependent histamine release from basophils of a fishallergic patient. Biological tests (e.g., histamine and leukotriene release assays) are difficult or impossible to perform with crude fish extracts, because the presence of mediators in these extracts can cause false-positive results (45). Based on our results it may now be possible to develop rCyp c 1.01-based effector cell tests that mimic clinical symptoms better than measurements of serum IgE Abs.…”

Section: Discussionmentioning

confidence: 93%

Recombinant Carp Parvalbumin, the Major Cross-Reactive Fish Allergen: A Tool for Diagnosis and Therapy of Fish Allergy

Swoboda¹,

Bugajska-Schretter²,

Verdino

et al. 2002

The Journal of Immunology

220

168

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IgE-mediated reactions to fish allergens represent one of the most frequent causes of food allergy. We have constructed an expression cDNA library from carp (Cyprinus carpio) muscle in phage λgt11 and used serum IgE from a fish allergic patient to isolate 33 cDNA clones that coded for two parvalbumin isoforms (Cyp c 1.01 and Cyp c 1.02) with comparable IgE binding capacities. Both isoforms represented calcium-binding proteins that belonged to the β-lineage of parvalbumins. The Cyp c 1.01 cDNA was overexpressed in Escherichia coli, and rCyp c 1.01 was purified to homogeneity. Circular dichroism analysis and mass spectroscopy showed that rCyp c 1.01 represented a folded protein with mainly α-helical secondary structure and a molecular mass of 11,416 Da, respectively. rCyp c 1.01 reacted with IgE from all fish-allergic patients tested (n = 60), induced specific and dose-dependent basophil histamine release, and contained most of the IgE epitopes (70%) present in natural allergen extracts from cod, tuna, and salmon. Therefore, it may be used to identify patients suffering from IgE-mediated fish allergy. The therapeutic potential of rCyp c 1.01 is indicated by our findings that rabbit Abs raised against rCyp c 1.01 inhibited the binding of IgE (n = 25) in fish-allergic patients to rCyp c 1.01 between 35 and 97% (84% mean inhibition) and that depletion of calcium strongly reduced IgE recognition of rCyp c 1.01. The latter results suggest that it will be possible to develop strategies for immunotherapy for fish allergy that are based on calcium-free hypoallergenic rCyp c 1.01 derivatives.

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Section: Discussionmentioning

confidence: 93%

Recombinant Carp Parvalbumin, the Major Cross-Reactive Fish Allergen: A Tool for Diagnosis and Therapy of Fish Allergy

Swoboda¹,

Bugajska-Schretter²,

Verdino

et al. 2002

The Journal of Immunology

220

168

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“…Previous exposure to protamine through use of protamine-containing insulins (NPH: neutral protamine Hagedorn) or during heparin neutralization, vasectomy and fish allergy have been proposed to predispose to the development of untoward reactions from the subsequent use of this drug (191,194,195). However, these findings could not be confirmed (196,197). Although skin tests with protamine may be helpful in identifying a possible IgE-mediated response in selected cases, these tests must be interpreted with caution because they do not necessarily predict clinical sensitivity and do not identify all patients at risk (198).…”

Section: Protamine and Heparinsmentioning

confidence: 88%

Anaphylaxis during anaesthesia: diagnostic approach

Ebo¹,

Fisher²,

Hagendorens³

et al. 2007

Allergy

195

197

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Anaesthesiologists administer several drugs while providing general anaesthesia. Many of these drugs can elicit adverse drug reactions that fall apart into two major types. First, reactions that are usually dose-dependent and related to the pharmacological properties of the drug and/or its metabolites. Second, reactions that are unrelated to the drug's pharmacological characteristics and that are less dose-dependent. These reactions comprise drug intolerance, idiosyncratic reactions and drug-induced immune-mediated allergic and nonimmune-mediated so-called pseudo-allergic or anaphylactoid reactions. The terms anaphylactic and anaphylactoid, however, have been used inconsistently in the literature. Therefore, the nomenclature task force set up by the European Academy of Allergy and Immunology (EAACI) has proposed that anaphylactic-type reactions should be reclassified into allergic anaphylaxis and nonallergic anaphylaxis. Allergic anaphylaxis being further subdivided in IgE-mediated and non-IgE-mediated reactions (1).The exact prevalence of anaphylaxis during anaesthesia is difficult to ascertain. The estimated overall frequency has been reported to vary between 1 in 3500 and 1 in 13 000 procedures in French series (2, 3) and between 1 in 10 000 and 1 in 20 000 in an Australian study (4). The clinical manifestation of these reactions is not infrequently an almost immediate generalized response with bronchospasm and hypotension. The degree of severity varies and does not allow differentiation between an IgE-mediated or non-IgE mediated reaction resulting from nonspecific mediator release (5). The mortality from these reactions is in the range from 3 to 6%, and an additional 2% of patients experience significant residual brain damage (4).Diagnosis of anaphylaxis during anaesthesia is not always straightforward. It can be hampered as a broad spectrum of different drugs can elicit heterogeneous allergic and nonallergic reactions with distinct and sometimes unclear pathological mechanisms. Problems are certainly compounded as multiple drugs need to be administered during general anaesthesia. In addition, nonanaesthesia related drugs or procedures (e.g. disinfection) are sometimes administered/performed in the perioperative period and can also be the cause of an allergic reaction.In addition, none of the available diagnostic tests demonstrates absolute accuracy. False-positive test Correct management of anaphylaxis during anaesthesia requires a multidisciplinary approach with prompt recognition and treatment of the acute event by the attending anaesthesiologist, and subsequent determination of the responsible agent(s) with strict avoidance of subsequent administration of all incriminated and/or cross-reacting compounds.However, correct identification of the causative compound(s) and safe alternatives is not always straightforward and, too often, not done.This review is not intended to discuss acute management of anaesthesia-related anaphylaxis but summarizes the major causes of anaphylaxis during anaesthesia and the di...

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“…6,33 In addition, men who have undergone vasectomy develop antibodies against protamine. 7,8,31,34 A limitation of our study was that that we did not have available the types of antidiabetic treatment the patients received before hospital admission (insulin or oral hypoglycemic agents), and whether the patients had undergone vasectomy. Therefore, we can only describe the association of diabetes with an increased risk for development of these antibodies.…”

Section: Blood 11 April 2013 X Volume 121 Number 15 Clinical Relevamentioning

confidence: 99%

Anti–protamine-heparin antibodies: incidence, clinical relevance, and pathogenesis

Bakchoul¹,

H²,

Amiral³

et al. 2013

Blood

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Key Points• Immunization against protamine/heparin complexes was frequently observed in patients undergoing cardiac surgery.• Platelet-activating antiprotamine-heparin antibodies are a potential risk factor for early postoperative thrombosis and thrombocytopenia.Protamine, which is routinely used after cardiac surgery to reverse the anticoagulant effects of heparin, is known to be immunogenic. Observing patients with an otherwise unexplained rapid decrease in platelet count directly after protamine administration, we determined the incidence and clinical relevance of protamine-reactive antibodies in patients undergoing cardiac-surgery. In vitro, these antibodies activated washed platelets in a FcgRIIa-dependent fashion. Using a nonobese diabetic/severe combined immunodeficiency mouse model, those antibodies induced thrombocytopenia only when protamine and heparin were present but not with protamine alone. Of 591 patients undergoing cardiopulmonary bypass surgery, 57 (9.6%) tested positive for anti-protamine-heparin antibodies at baseline and 154 (26.6%) tested positive at day 10. Diabetes was identified as a risk factor for the development of anti-protamine-heparin antibodies. In the majority of the patients, these antibodies were transient and titers decreased substantially after 4 months (P < .001). Seven patients had platelet-activating, anti-protamine-heparin antibodies at baseline and showed a greater and more prolonged decline in platelet counts compared with antibody-negative patients (P 5 .003). In addition, 2 of those patients experienced early arterial thromboembolic complications vs 9 of 584 control patients (multivariate analysis: odds ratio, 21.58; 95% confidence interval, 2.90-160.89; P 5 .003). Platelet-activating antiprotamine-heparin antibodies show several similarities with anti-platelet factor 4-heparin antibodies and are a potential risk factor for early postoperative thrombosis. (Blood. 2013;121(15):2821-2827

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Evaluation of Patients at Risk for Protamine Reactions

Cited by 22 publications

References 0 publications

Recombinant Carp Parvalbumin, the Major Cross-Reactive Fish Allergen: A Tool for Diagnosis and Therapy of Fish Allergy

Recombinant Carp Parvalbumin, the Major Cross-Reactive Fish Allergen: A Tool for Diagnosis and Therapy of Fish Allergy

Anaphylaxis during anaesthesia: diagnostic approach

Anti–protamine-heparin antibodies: incidence, clinical relevance, and pathogenesis

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