Oropharyngeal angioneurotic edema due to recombinant tissue plasminogen activator following massive pulmonary thromboembolism

Short communication

Oropharyngeal angioneurotic edema due to recombinant tissue plasminogen

activator following massive pulmonary thromboembolism

Perihan Ekmekçi

⁎

, Züleyha Kazak Bengisun

, Baturay Kansu Kazbek

, Halit Akmansu

,

Güçlü Kaan Beriat

, Arif Hikmet Süer

a_{Ufuk University Faculty of Medicine, Dr. Rıdvan Ege Hospital. Anesthesiology and Reanimation, Turkey} b_{Ufuk University Faculty of Medicine, Dr. Rıdvan Ege Hospital. Ear, Nose and Throat, Turkey}

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 24 February 2011

Received in revised form 11 April 2011 Accepted 28 April 2011

Available online 12 May 2011 Keywords:

rTPA

Pulmonary embolism Oropharyngeal edema Anaphylactoid reaction

Although hypersensitivity reactions secondary to recombinant tissue plasminogen activator (rtPA) are rarely encountered, they may have important consequences. In this case presentation, oropharyngeal angioneurotic edema due to rtPA following pulmonary thromboembolism is presented. On the 4th hour of initiation of treatment, throat pain, laryngeal stridor and expansive edema in the neck ensued, upon which the patient was intubated and mechanically ventilated. The patient was extubated after herfindings showed a remission on the 48th hour of his inotropic, antihistaminic and intravenous corticosteroid therapy.

© 2011 Elsevier B.V. All rights reserved.

1. Introduction

Hypersensitivity reactions following recombinant tissue plasmin-ogen activator (rtPA) has an incidence of %0.2–2 and is a rare but potentially important clinical situation[1]. The incidence is reported to be different for different situations; its incidence is 1.9% after acute ischemic stroke[2]. Although the definite mechanism of this situation which has the clinic of anaphylactoid hypersensitivity is not clear, the activation of kinin and the complement cascade has been implied

[3,4]. In this case report oropharyngeal angioneurotic edema due to recombinant tissue plasminogen activator following massive pulmo-nary thromboembolism is discussed.

2. Case report

Written informed consent was obtained from the patient con-cerning this publication. Recombinant tissue plasminogen activator therapy was given to a 65 year old female patient who had hypertension and rheumatoid arthritis due to a massive pulmonary embolism following revision total hip replacement surgery. The patient was using valsartan, hydrochlorothiazide, colchicine, sulfasa-lazine and methotrexate in the preoperative period. The patient was given prophylactic fractionated heparin treatment (400 IU) as a routine process. Computerized tomography angiography revealed a

massive embolus which originated from the middle section of the right pulmonary artery and extended to the division of lobar arteries. The patient whose echocardiography results showed that the right atrial motion was limited, was given an infusion of 100 mg rtPA and heparin at the same time on the tenth postoperative hour. There was massive bleeding for the operation site after rtPA and the patient was given 12 units of erythrocyte suspension and 1 unit of fresh frozen plasma. Dobutamine and norepinephrine infusions were started. The origin of the embolus was shown to be the right femoral vein in lower extremity venous doppler ultrasonography. Four hours after the start of rtPA therapy, there was throat pain, laryngeal stridor, diffuse edema in the neck and desaturation. The patient had a Glasgow coma scale of 15, was intubated under sedation and mechanical ventilation support was initiated. Diffuse oropharyngeal edema was observed during laryngoscopy. The patient was given H1 and H2 blockers,

methyl-prednisolone 1.5 mg/kg intravenously and this treatment was continued on the second day because there was no improvement of the oropharyngeal edema. Chest radiography revealed that the trachea was not deviated and there was no evidence of mediastinal compression. The patient received mechanical ventilation support for 36 hours, after which the patient was extubated following the establishment of hemodynamic stability.

3. Discussion

Hypersensitivity reactions caused by recombinant tissue plasmin-ogen activator are potentially lethal situations, which are character-ized by anaphylactoid reactions and do not have a fully understood

International Immunopharmacology 11 (2011) 1384–1385

⁎ Corresponding author at: Konya Yolu Mevlana Blv. 86/88 06520 Balgat Ankara, Turkey. Tel.: + 90 3122044098; fax: +90 3122872390.

E-mail address:erdogduperi@gmail.com(P. Ekmekçi).

1567-5769/$– see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2011.04.020

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International Immunopharmacology

mechanism of action. rtPA catalyses the synthesis of plasmin from plasminogen. Plasmin causes direct activation of the complement and the kinin cascade. Complement activation causes mast cell degranu-lation while kinin cascade activation causes an increase in bradykinin levels and thus vasodilatation and anaphylactoid reaction clinic.

In a study conducted by Ottomeyer et al. which included 2287 patients, it was shown that neurological symptoms may accompany the hypersensitive state. In the mentioned study, intravenous thrombolysis was carried out in 312 patients, 7 patients developed neurological symptoms out of 8 who had oropharyngeal angioneuro-tic edema[5]. It is reported that neurological symptoms are more common in patients whose lesions involve the insular cortex and basal ganglia [6]. Additionally neurological symptoms such as dementia and syncope can be seen in massive pulmonary thrombo-embolism. In our case, neurological symptoms were absent.

Previous literature shows that a history of angiotensin converting inhibitors (ACE-I) causes a 13.6 fold increase in angioneurotic edema following rtPA [7,8]. These agents, who themselves may cause angioneurotic edema[9], inhibit ACE, which is a kininase II enzyme. The inhibiton of kininase II causes a reduction in bradykinin degradation which in turn causes vasodilatation.

Angioedema is also reported following losartan, which is an angiotensin receptor blocker (ARB) [7]. Although the underlying mechanism is not clear, it is proposed that ARB stimulates angiotensin receptors and causes an increase in tissue bradykinin levels [10]. Similarly, angioedema has been reported following hydrochlorothi-azide[11].

In vitro studies show that anaphylaxis causes an increase in endogenous tPA levels and C3a, C4a and C5a levels significantly increase following alteplase[3]. There was no increase in levels of immunoglobulin subtypes (Ig A, G, E, and M) or complement. It is believed that the reaction against rtPA which is an endogenous protein and thus has a low level of antigenity is caused by a direct activation of the complement and the kinin cascade, rather than an IgE mediated mechanism as in common anaphylaxis.

Considering the massive blood transfusion in this patient, a transfusion reaction or an allergic reaction to unfractionated heparin should be included in differential diagnosis. But the fact that orolingual edema is absent in transfusion reaction clinic and orolingual edema following rtPA in patients using ARB has been

established in the literature, the clinical situation has been associated with valsartan. However, the fact that pulmonary embolism devel-oped under fractionated heparin treatment and heparin induced hypersensitivity reactions are mostly type II and type IV reactions, and the fact that isolated orolingual edema has not been reported with heparin, it was omitted in the differential diagnosis[12].

In this case report, oropharyngeal angioedema due to rtPA following massive pulmonary embolism is discussed. If rtPA usage is planned in patients who are on ACE-I or ARBs, Mallampati score must be taken into consideration, preparations for difficult intubation must be made, the tongue and the oropharynx must be evaluated carefully in the hours following the initiation of treatment and this rare but potentially lethal situation must be kept in mind.

References

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[8] Pancioli A, Brott T, Donaldson V, Miller R. Asymmetric angioneurotic edema associated with thrombolysis for acute stroke. Ann Emerg Med 1997;30(2):227–9. [9] Agostoni A, Cicardi M, Cugno M, Zingale LC, Gioffré D, Nussberger J. Angioedema due to angiotensin-converting enzyme inhibitors. Immunopharmacology 1999;44 (1–2):21–5.

[10] Irons BK, Kumar A. Valsartan-induced angioedema. Ann Pharmacother 2003;37 (7–8):1024–7.

[11] Ruscin JM, Page RL, Scott J. Hydrochlorthiazide-induced angioedema in a patient allergic to sulfonamide antibiotics: evidence from a case report and a review of the literature. Am J Geriatr Pharmacother 2006;4(4):325–9.

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