Streptokinase-inducedAnaphylaxis

Joey A. TabulaMarvin L. Mendoza

30 April 2015

Outline

• Definition of anaphylaxis/anaphylactic shock• Diagnosis and management of anaphylaxis• Streptokinase-induced reactions including

anaphylaxis/anaphylactic shock• Kounis Syndrome

History of Present Illness

• EM, 40-year old male patient• Admitted for sudden, severe chest pain• 10-day history of intermittent mild chest pain• No previous consults or medications taken

History of Present Illness

• 3 hours PTA, patient experienced sudden chest pain, NRS 10/10 associated with dyspnea and diaphoresis consult

History of Present Illness

• PMHx: HPN on amlodipine, no known food/drug allergy, previous hospitalizations nor previous streptokinase use

• FHx: denies atopic diseases• P&SHx: cigarette smoker and occasional alcohol

beverage drinker; denies illicit drug use

History of Present Illness

Initial 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

Course

• Pre-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

Course

• Other 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

Course

Anaphylaxis from Streptokinase• Streptokinase infusion discontinued• Hydration with 1L saline• Delivered Epinephrine 1:1000 units 0.3cc IM• BP improved to 90/60 MICU admission• Referred to Allergy Service

Course

• Allergy Service• Dx: ADE (anaphylaxis) to streptokinase–Hydrocortisone 100mg IV q12–Diphenhydramine 50mg IV q8 RTC–Ranitidine 50mg IV q8 RTC–Observe for 4 hours for biphasic reactions

Course

• No recurrence of hypotension• No new complaints• IV antihistamines shifted to oral form• Hydrocortisone shifted to Prednisone• Completed 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

Anaphylaxis

• In 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

IS THIS ANAPHYLACTIC SHOCK?

Management

Anaphylaxis is a medical EMERGENCY.

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

Streptokinase (SK)

• Thrombolytic agent • Enzyme secreted by streptococci • Binds and activates plaminogen• Compared with other thrombolytics, higher

incidence of allergic reactions (Dundar et al. Q J Med, 2003.

SK-induced Reactions

• Sparse discussion in literature• B type: not common, unpredictable• 1.7-18% 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.

SK-induced Minor Reactions

• Etiology unknown• Not antibody-mediated– Low titers of antistreptokinase IgG among patients who

reacted to streptokinase• May involve complement activation– Low levels of total complement (C3, C4, C3d) 1 year

post-reaction among patients who reacted to streptokinase

Lynch et al. Clin Exp Immunol, 1993.

SK-induced Anaphylaxis and Serum-Sickness

• Anaphylaxis– Mast cell activation– Can be mediated by IgE or C3a and C5a– Etiology not clear

• Serum Sickness– Related to circulation antibodies to SK

SK-induced Anaphylaxis

• Case Reports and Literature Review– Presented 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)

AnaphylaxisDrug Cases per 100,000 exposed

patientsAnalgesicsAntibiotics

5-15

Parenteral Penicillin 32BloodDextranPentoxifyllineContrast media

35-95

Streptokinase 378 (150)Plasma 284

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

Related or Unrelated?

Myocardial Infarction

Anaphylaxis

Allergy Myocardial Infarction

Kounis Syndrome

• Also known as coronary hypersensitivity disorder• First case in 1950 with penicillin• 1991 – Kounis and Zavras made detailed

description– Syndrome of allergic angina and allergic MI

Kounis NG. Clin Ther, 2013.

Subtypes

• Type I – normal or nearly normal coronary arteries without risk factors for coronary artery disease

• Type II – with angiographic evidence of CAD when the allergic events induce plaque erosion or rupture

• Type III - coronary artery stent thrombosis in which aspirated thrombus specimens demonstrate eosinophils and mast cells

Causality

• Drugs (even losartan)• Scombroid syndrome or histamine fish poisoning– Fish 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 histamine

• Gelofusine– component of various vaccines for children and constitutes the

main cause of sensitization in children.• Latex

Treatment for Type I

• Treatment of the allergic event alone may abolish symptoms.

• Hydrocortisone 1 to 2 mg/kg/d IV• H1 and H2 antihistamines, such as diphenhydramine

(1–2 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 II• ACS 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 II

• Opioids such as morphine, codeine, and meperidine– extreme caution in patients with Kounis syndrome because

they may induce massive mast-cell degranulation and aggravate allergic reaction.

• Paracetamol– not 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 III

• ACS 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 measures should be applied.• If these measures fail, stent extraction seems unavoidable.

Thanks!