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Interesting Case Conference

Interesting Case Conference. January 24, 2014 Charles Stoudenmire, MD Benjamin Chamberlain, MD. Patient 1. 59-year-old healthy male stem cell donor No history of hypertension Recent “sinus infection” improving after taking azithromycin

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Interesting Case Conference

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  1. Interesting Case Conference January 24, 2014 Charles Stoudenmire, MD Benjamin Chamberlain, MD

  2. Patient 1 • 59-year-old healthy male stem cell donor • No history of hypertension • Recent “sinus infection” improving after taking azithromycin • Only current complaints are headache and hip pain (5/10) since starting Neupogen and some nervousness about his procedure

  3. The Events • Prior to IV insertion, vital signs are as follows: • BP: 162/92 mmHg • HR: 108 bpm • Temp: 97.8 • 15 minutes later: • BP: 168/102 • HR: 90

  4. The Plan • 0.2 mg of clonidine PO times one dose • 0.5 mg of Ativan (lorazepam) PO times one dose • Recheck blood pressure in 30 minutes

  5. Reassessment • 30 minutes later: • BP: 158/96 mmHg • 4 minutes after that: • BP: 154/96 mmHg • HR: 102 bpm • Patient says headache is gone and denies anxiety

  6. After 15 more minutes • BP: 138/85 mmHg • HR: 102 bpm • IVs placed and procedure started

  7. End Result • IV-related pain and distress • Two additional doses of 0.5 mg Ativan • One 5 mg dose of PO oxycodone • Patient slept peacefully through remainder of procedure • Stable upon departure.

  8. Clonidine • α-2 adrenergic receptor agonist • α-2 receptors cause feedback inhibition • ↓ release of norepinephrine • Abrupt cessation of chronic therapy may cause rebound hypertension http://servingnature.blogspot.com/2013/03/ans-receptors.html

  9. References • G G Geyskes, P Boer, and E J Dorhout Mees. Clonidine withdrawal. Mechanism and frequency of rebound hypertension. Br J Clin Pharmacol. 1979 January; 7(1): 55–62. • http://servingnature.blogspot.com/2013/03/ans-receptors.html

  10. Patient 2

  11. Patient 2 • 44-year-old female with history of Grave’s disease • Has had rapidly progressive, nonfluctuating cognitive decline over past 2-3 months, preceded by increased obsessive-compulsive behaviors • Recent MRI with findings “highly suspicious for Creutzfeld-Jakob disease” • EEG also suggestive of CJD

  12. Creutzfeld-Jakob Disease • Neurodegenerative disease resulting from accumulation of prions • CJD accounts for >90% of sporadic prion disease • Types: Sporadic (85-95%), Familial (5-15%), Variant (BSE), Iatrogenic • As of 2013, only 3 vCJD cases confirmed in US

  13. Prions • Infectious proteins • Cause neuronal loss, proliferation of glial cells, and vacuolation of neuropil (“spongiform appearance”)

  14. Prion Mechanism

  15. More History • Consumed fried brains in 1980’s overseas • Was in London “briefly” in 1983 and 2013 • Blood transfusion in 2005 for placenta accreta • Shared lab space with a prion expert who worked on proteins related to prions

  16. The Question • Could her development of prion disease be related to the blood transfusion she received here in 2005? • 2 units leukoreduced pRBCs (O positive)

  17. Transmission via Transfusion • No documeted cases of transmission via transfusion of sporadic type. • In the UK, 4, possibly 5, cases of development of vCJD are attributed to blood transfusions • Recipients developed vCJD after receiving blood from donors who also later developed vCJD. • No reports in US

  18. FDA Criteria for Donor Deferral (2010) • Residence in the U.K. for 3 months or more, between 1980 and 1996. (> 6 months est. 1999) • Military personnel (current and former), and their dependents, who spent time in military bases in northern Europe 1980-1990, or southern Europe (1980-1996), for 6 months or more. • Donors who lived in France for 5 years or more, between 1980 and the present. • Donors who received a transfusion in the U.K. between 1980 and the present. • Blood donors who lived in Europe for 5 years or more, between 1980 and the present.

  19. Calculated Effects of these Guidelines • Eliminate an estimated total 90% of overall risk (calculated by "risk-weighted" person-days of exposure to infected beef) • Decrease the number of donors ~ 5% nationwide.

  20. So is this transfusion-related? • 85-95% of cases are the sporadic type • No documented cases of transmission via transfusion • 225 cases vCJD reported worldwide • Only 3 cases of vCJD documented in US • 2 of these lived in the UK > 6 months (1980-96) • 1 born and raised in Saudi Arabia • Only 4, possibly 5, cases related to transfusion • FDA instituted exclusionary criteria in 1999; Patient’s transfusion was in 2005.

  21. Probably Not

  22. References • Dorsey K, Zou S, Schonberger LB, Sullivan M, Kessler D, Notari E 4th, Fang CT, Dodd RY. Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US surveillance study. Transfusion. 2009;49(5):977. • Puoti G, Bizzi A, Forloni G, Safar JG, Tagliavini F, Gambetti P. Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol. 2012 Jul;11(7):618-28. • FDA: Questions and Answers on "Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products" • Hunt, Richard. “Slow Virus Diseases of the Nervous System”. Chapter 23, Virology. Microbiology and Immunology Online. University of South Carolina School of Medicine. 2006 • Chohan G, Llewelyn C, Mackenzie J, Cousens S, Kennedy A, Will R, Hewitt P. Variant Creutzfeldt-Jakob disease in a transfusion recipient: coincidence or cause? Transfusion. 2010;50(5):1003. • Variant CJD Cases Worldwide. The National CJD Research and Surveillance Unit. The University of Edinburgh. 2013

  23. Patient 3

  24. Patient 3 • 27-year-old African American female with Sickle Cell Disease • Highly alloimmunized from many past transfusions • Admitted 1/14/14 for pain crisis • Developed fever and leukocytosis in setting of persistent, though improved, pneumonia

  25. Therapy • Started on vancomycin and aztreonam • Creatinine 4.45 mg/dL on 1/18/14 • Was 0.56 on 1/16/14 • Rose to maximum of 6.9 mg/dL • Acute interstitial nephritis + anemia + volume depletion?

  26. Hematocrit from Admission

  27. Patient’s Blood Profile • A positive • Antibodies: anti-Jkb, -K1, -M, -S, -C, Bg • Her anti-M determined significant for effect at 37 C. • Patient also E-, FyA – • Compatible units…

  28. Odds of compatibility • 0.15 = 7 0.15x = 700  x = 700 • 100 x 0.15 • x = 4666.6 units

  29. What happened • Received 7 units over admission • 2 were Fya positive • Most recent unit received from ARC on 1/23/14 had incompatible crossmatch, both with latest patient sample and original patient sample… anti-Bg?

  30. Reference • Harmening, Denise M. Modern Blood Banking and Transfusion Practices. 5th ed. F.A. Davis Co. Philadelphia. 2005

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