1. Why did vitamin B12 deficiency respond to plasmapheresis?
J. Matthew Rhinewalt, MD, PGY-4
Internal Medicine/Pediatrics
University of MS Medical Center
Jackson, MS
Why did vitamin B12 deficiency respond to plasmapheresis?

2. Introduction Vitamin B12 deficiency: Multi-organ dysfunction
Variety of clinical presentations
May present clinically similar to thrombotic thrombocytopenic purpura (TTP)
Vitamin B12 is needed for the synthesis of Deoxy ribo
Nucleic Acid (DNA) and division of blood cells.
Deficiency of vitamin B12 leads to an arrest in the
maturation of nucleated precursors and results in
hemolysis in the bone marrow [3]. This manifests
clinically as hemolytic anemia with indirect
hyperbilirubinemia and an elevated serum LDH levels [3].
Serum LDH levels are higher in vitamin B12 deficiency [4]
than peripheral hemolysis from TTP.
An increase in the RBC membrane rigidity and a decrease
in erythrocyte deformability were reported in B12
deficiency [5]. Deficiency of Vitamin B12 also results in an
elevated serum homocysteine [6]. High homocysteine in
the serum causes endothelial dysfunction [6]. The
biological effects of endothelial dysfunction are
vasoconstriction, increased platelet aggregation, activation
of coagulation system and monocyte adhesion to the
endothelium [6]. This leads to fragmentation of
erythrocytes to schistocytes as seen in our patient.
Schistocytes can also be seen in patients with
preeclampsia, malignant hypertension, renal failure,
mechanical heart valves, vitamin B12 deficiency and
occasionally in normal individuals. Schistocytes are seen
in life threatening conditions like TTP/HUS and DIC. TTP
is differentiated from DIC by presence of normal
coagulation parameters (prothrombin time, partial
thromboplastin time, and serum fibrinogen).
(North American Journal of Medical Sciences 2011 July, Volume 3. No. 7.)

3. Case Description – History
62 y/o man
CC: confusion
HPI:
3 days of confusion per emergency medical personnel
pt unable to answer any questions upon presentation and no family present
PMH: type 2 diabetes, seizure disorder, alcoholism, illicit drug use

4. Case Description – Physical Exam
Pertinent Physical Exam
Temperature 100.5°F
Weight 185lbs
Sleepy/confused
Jugular venous pressure 10cm
Liver edge 3cm below right costal margin
No evidence of bleeding or petechiae
Negative bedside fecal occult blood testing

5. Case Description - Labs
Pertinent (+) labs:
WBC 3.3
LDH >2500
Hgb 5
haptoglobin <10
Hct 15%
total bilirubin 2.5 (indirect 1.7)
MCV 108
Plt 58,000
Creatinine 1.6
Retic count 0.9% (corrected)
(baseline 0.8)(baseline 0.7)

6. Case Description - Labs
Pertinent (-/nrl) labs:
Glucose
Ammonia
Urine drug screen
Fecal occult blood testing
Alcohol level
Creatine kinase
Prothrombin time
Troponin

7. Case Description - Labs
Blood Smear:
Hypersegmented neutrophils
Rare schistocytes
Many tear drop cells
Moll. NEJM. 1996; 335:323. August 1, 1996.

8. Problems Fever Hemolytic/Macrocytic Anemia Low Reticulocyte Count
Thrombocytopenia
Altered Mental Status
Acute Kidney Injury
History of Alcoholism, Type 2 Diabetes, Seizure Disorder

9. Initial Differential Diagnosis
#1 - Thrombotic Thrombocytopenic Purpura
#2 - Vitamin B12 Deficiency
#3 - Leukemia / Bone Marrow Malignancy

10. Management Hematology consult
Plasmapheresis for possible TTP while awaiting labs

11. Therapy 4 units PRBC transfusion: hospital day 1
Plasmapheresis: hospital day 1-3
(12 bags FFP each treatment)

12. Results Clinical improvement after first plasmapheresis: hemolysis
mental status
renal function
ADMIT
HOSP DAY 2
LDH
>2500
979
Haptoglobin
<10 15
Bilirubin
3.4
2.6
Creatinine
1.6
0.98

13. Interesting Results AdamTS13 activity normal Folate RBC level normal
Leukemia/lymphoma panel normal
Vitamin B12 level 30pg/mL
(resulted on hospital day 3)
He later had an intrinsic factor blocking antibody positive result and was therefore kept on IM/parenteral vitamin B12.

14. Continued Management
On hospital day 3:
Vitamin B mcg IM daily

15. Upon Discharge (Hospital Day 8)
PE: mental status back to baseline
Labs:
Creatinine back to baseline
Hgb 10
Platelet count 124,000
Reticulocyte count 13% (corrected)
LDH 777

16. Why did he rapidly improve with plasmapheresis?

17. How much vitamin B12 is in FFP?
Unable to locate a reference
Is it degraded during processing?

18. How much vitamin B12 is in FFP?
Thank you to Dr. Asfour
UMMC blood bank pathologist
Random sampling of 4 bags of FFP for B12 levels
Results: 300 – 500 pg/mL
Our patient’s level was 30 pg/mL

19. Clinical Impact
Vitamin B12 levels in FFP were comparable to serum levels of non-deficient patients
need for baseline B12 level
signs & symptoms of vitamin B12 deficiency may likely improve if given FFP

20. Thank You
Mohamed A. Asfour, MD
Taylor Pruett, MD
John C. Henegan, MD