streptokinase anaphylaxis

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Streptokinase-inducedAnaphylaxis

Joey A. TabulaMarvin L. Mendoza

30 April 2015

OutlineDefinition of anaphylaxis/anaphylactic shockDiagnosis and management of anaphylaxisStreptokinase-induced reactions including anaphylaxis/anaphylactic shockKounis Syndrome

History of Present IllnessEM, 40-year old male patientAdmitted for sudden, severe chest pain10-day history of intermittent mild chest painNo previous consults or medications taken

History of Present Illness3 hours PTA, patient experienced sudden chest pain, NRS 10/10 associated with dyspnea and diaphoresis consult

History of Present IllnessPMHx: HPN on amlodipine, no known food/drug allergy, previous hospitalizations nor previous streptokinase useFHx: denies atopic diseasesP&SHx: cigarette smoker and occasional alcohol beverage drinker; denies illicit drug use

History of Present IllnessInitial Physical Examination (ER)BP 130/90, HR 86, RR 20, Temp afebrileAwake, not in distressEqual chest expansion and clear breath soundsAdynamic precordium, normal rate and regular rhythm, no heave/thrillFull and equal pulses; no cyanosis

Acute STEMI Inferior Wall , Killip IHypertension Stage II

CoursePre-medicated with Diphenhydramine 50mg IV and Hydrocortisone 100mg IV 30 minutes prior to thrombolysis

Given Streptokinase 1.5M units + 100 cc saline in soluset to infuse for one hour

CourseOther ACS meds given: aspirin, clopidogrel, enoxaparin, captopril, carvedilol, atorvastatin, lactulose

After 30 minutes on streptokinase, patient developed hypotension (BP 80/50) and vomiting; no dyspnea/wheezing, flushing, rash, pruritus

CourseAnaphylaxis from StreptokinaseStreptokinase infusion discontinuedHydration with 1L salineDelivered Epinephrine 1:1000 units 0.3cc IMBP improved to 90/60 MICU admissionReferred to Allergy Service

CourseAllergy ServiceDx: ADE (anaphylaxis) to streptokinaseHydrocortisone 100mg IV q12Diphenhydramine 50mg IV q8 RTCRanitidine 50mg IV q8 RTCObserve for 4 hours for biphasic reactions

CourseNo recurrence of hypotensionNo new complaintsIV antihistamines shifted to oral formHydrocortisone shifted to PrednisoneCompleted 5 days of antihistamines and steroid

Anaphylaxis

a serious, life-threatening generalized or systemic hypersensitivity reaction and a serious allergic reaction that is rapid in onset and might cause death

World Allergy Organization Guidelines for the Assessment and Management of AnaphylaxisF. Estelle R. Simons, MD, FRCPC et al, 2011

AnaphylaxisIn public health terms, anaphylaxis is considered to be an uncommon cause of death (underdiagnosis, under-reporting)

The true global rate of occurrence of anaphylaxis from all triggers in the general population is unknown

Pathophysiology

Clinical Criteria

World Allergy Organization Guidelines for the Assessment and Management of AnaphylaxisF. Estelle R. Simons, MD, FRCPC et al, 2011

Symptoms and signs of anaphylaxis

1. Skin, subcutaneous tissue, and mucosaFlushing, itching, urticaria (hives), angioedema, morbilliform rash, pilor erectionPeriorbital itching, erythema and edema, conjunctival erythema, tearingItching of lips, tongue, palate, and external auditory canals; and swelling of lips, tongue, and uvulaItching of genitalia, palms, and soles2. RespiratoryNasal itching, congestion, rhinorrhea, sneezingThroat itching and tightness, dysphonia, hoarseness, stridor, dry staccato coughLower airways: increased respiratory rate, shortness of breath, chest tightness, deep cough, wheezing/bronchospasm, decreased peak expiratory flowCyanosisRespiratory arrest3. GastrointestinalAbdominal pain, nausea, vomiting (stringy mucus), diarrhea, dysphagia4. Cardiovascular systemChest painTachycardia, bradycardia (less common), other arrhythmias, palpitationsHypotension, feeling faint, urinary or fecal incontinence, shockCardiac arrest5. Central nervous systemAura of impending doom, uneasiness (in infants and children, sudden behavioral change, eg. irritability, cessation of play, clinging to parent); throbbingheadache (pre-epinephrine), altered mental status, dizziness, confusion, tunnel vision6. OtherMetallic taste in the mouthCramps and bleeding due to uterine contractions in females17

IS THIS ANAPHYLACTIC SHOCK?

Management

Anaphylaxis is a medical EMERGENCY.

Remove exposure to the trigger, i.e discontinue IV medication

Epinephrine should be injected by the intramuscular route in the mid-anterolateral thigh as soon as anaphylaxis is diagnosed or strongly suspected, in a dose of 0.01 mg/kg of a 1:1,000 (1 mg/mL) solution, to a maximum of 0.5 mg in adults (0.3 mg in children).

Depending on the severity of the episode and the response to the initial injection, the dose can be repeated every 515 minutes, as needed. Most patients respond to 1 or 2 doses of epinephrine injected intramuscularly promptly; however, more than 2 doses are occasionally required.

Failure to inject it promptly is potentially associated with fatality, encephalopathy because of hypoxia and/or ischemia, and biphasic anaphylaxis in which symptoms recur within 172 hours (usually within 8 10 hours) after the initial symptoms have resolved, despite no further exposure to the trigger.20

Streptokinase (SK)Thrombolytic agent Enzyme secreted by streptococci Binds and activates plaminogenCompared with other thrombolytics, higher incidence of allergic reactions (Dundar et al. Q J Med, 2003.

SK-induced ReactionsSparse discussion in literatureB type: not common, unpredictable1.7-18% experience reactions mostly minor (rigors, rash, minor angioedema)Significant proteinuria in first 24 hours (0.45g/L) and resolved by day 5

Lynch et al. Clin Exp Immunol, 1993. Lynch et al. Am J Cardiol, 1994.De Oliviera et al. Ar Bras Cardiol, 2005.

Article not available22

SK-induced Minor ReactionsEtiology unknownNot antibody-mediatedLow titers of antistreptokinase IgG among patients who reacted to streptokinaseMay involve complement activationLow levels of total complement (C3, C4, C3d) 1 year post-reaction among patients who reacted to streptokinaseLynch et al. Clin Exp Immunol, 1993.

SK-induced Anaphylaxis and Serum-SicknessAnaphylaxisMast cell activationCan be mediated by IgE or C3a and C5aEtiology not clearSerum SicknessRelated to circulation antibodies to SK

SK-induced AnaphylaxisCase Reports and Literature ReviewPresented with profound hypotension and rapidly spreading erythematous rash (Tisdale et al. DICP, 1989)CP arrest after streptokinase (Bednarzyk et al. DICP, 1989)Review of literature: 5 more cases (Bednarzyk et al. DICP, 1989)

AnaphylaxisDrugCases per 100,000 exposed patientsAnalgesicsAntibiotics5-15Parenteral Penicillin32BloodDextranPentoxifyllineContrast media35-95Streptokinase378 (150)Plasma284

ICSSA. Pharmacoepidemiol Drug Saf, 2003.De Oliviera et al. Ar Bras Cardiol, 2005.

Related or Unrelated?Myocardial Infarction

Anaphylaxis

Allergy Myocardial Infarction

Kounis SyndromeAlso known as coronary hypersensitivity disorderFirst case in 1950 with penicillin1991 Kounis and Zavras made detailed descriptionSyndrome of allergic angina and allergic MI

Kounis NG. Clin Ther, 2013.

SubtypesType I normal or nearly normal coronary arteries without risk factors for coronary artery diseaseType II with angiographic evidence of CAD when the allergic events induce plaque erosion or ruptureType III - coronary artery stent thrombosis in which aspirated thrombus specimens demonstrate eosinophils and mast cells

CausalityDrugs (even losartan)Scombroid syndrome or histamine fish poisoningFish flesh contains the amino acid histidine, and when fish infected with gram-negative bacteria containing the enzyme histidine decarboxylase is ingested, then this enzyme converts histidine into histamineGelofusinecomponent of various vaccines for children and constitutes the main cause of sensitization in children.Latex

Treatment for Type ITreatment of the allergic event alone may abolish symptoms. Hydrocortisone 1 to 2 mg/kg/d IVH1 and H2 antihistamines, such as diphenhydramine (12 mg/kg) and ranitidine (1 mg/kg)Vasodilators such as CCB and nitrates may abolish hypersensitivity-induced vasospasm. Nitroglycerin may cause hypotension and tachycardia

Treatment for Type IIACS protocol with corticosteroids and antihistamines. Vasodilators such as nitrates and CCBs are given when appropriate. Beta-blockers may exaggerate coronary spasm Epinephrine may aggravate ischemia and worsen coronary vasospasm in Kounis syndrome. In severe cases, sulfite-free epinephrine given IM is preferable because it has a faster onset of action and maintains a more stable concentration compared with the SC route (recommended IM dose, 0.2 0.5 mg [1:1000]). In patients receiving beta-blockers, epinephrine may be ineffective.

Treatment for Type IIOpioids such as morphine, codeine, and meperidineextreme caution in patients with Kounis syndrome because they may induce massive mast-cell degranulation and aggravate allergic reaction. Paracetamolnot recommended, especially by IV, because it might cause severe hypotension due to a reduction in cardiac output. Fentanyl and its derivatives are weak mast-cell triggers.

Treatment for Type IIIACS protocol with urgent aspiration of intrastent thrombus, followed by histologic examination of aspirated material and staining for eosinophils (hematoxylin and eosin) and mast cells (Giemsa) should be undertaken. In patients in whom allergic symptoms develop after stent implantation,antihistamines together with corticosteroids and mast-cell stabilizers may relieve the symptoms. If symptoms persist, the underlying cause should be ascertained and desensitization