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: 4 minutes after that: BP: 158/96 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

9. References
G G Geyskes, P Boer, and E J Dorhout Mees. Clonidine withdrawal. Mechanism and frequency of rebound hypertension. Br J Clin Pharmacol January; 7(1): 55–62.

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 (> 6 months est. 1999)
Military personnel (current and former), and their dependents, who spent time in military bases in northern Europe , or southern Europe ( ), 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 ( )
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 Jul;11(7):
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
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 x = 4666.6 units A/O Jkb- K1- M- S- C- E- Fya-
overall
0.85
0.27
0.91
0.22
0.45
0.30
0.70
0.35
0.0015
0.15 = 7  x =  x =  x
x = 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