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?

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.)

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

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

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)

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

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

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

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

Management Hematology consult Plasmapheresis for possible TTP while awaiting labs

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

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

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.

Continued Management On hospital day 3: Vitamin B12 1000mcg IM daily

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

Why did he rapidly improve with plasmapheresis?

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

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

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

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