Diagnostic and Management Challenges of Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy in a Jehovah's Witness
Authors: Sharma Pritika , Vegunta Rathnamitreyee , Tariq Rehan , Steinberg Amir , Nelson John C. 
Published: December 2024

Introduction: This case highlights the challenges in distinguishing vitamin B12 deficiency-associated pseudo-thrombotic microangiopathy (pseudo-TMA) from thrombotic thrombocytopenic purpura (TTP).
Case Presentation: An otherwise healthy 26-year-old woman, a Jehovah's Witness, presented to urgent care with exertional dyspnea, fatigue, and weight loss and was referred to the ED for critically low hemoglobin (Hgb, 5.0 g/dL).
In the ED, she reported nausea, vomiting, and diarrhea for several weeks and a cruise to the Dominican Republic six weeks prior. She denied abnormal genitourinary, rectal, and cutaneous bleeding, coffee-ground emesis, bruising, rashes, abdominal pain, trauma, new medications, or tick exposure. She reported occasional alcohol use and denied smoking, substance use, and any family history of blood disorders.
On physical exam, she was ill-appearing and pale. No jaundice, extremity edema, joint swelling, or cardiac murmurs were noted. Significant lab findings include:

CBC
WBC 3.96k/µL, Hgb 4.2 g/dL, MCV 116.4 fL, Plt 44k/µL, ANC 1.58k/µL, reticulocyte (retic) count 4.97%
INR 1.06, APTT 25.1sec, fibrinogen 206 mg/dL

CMP
creatinine 0.78 mg/dL, total bilirubin 1.8 mg/dL, direct bilirubin 0.6 mg/dL, LDH 4966 U/L, haptoglobin &lt;8 mg/dL

Other
Normal TSH. Negative rheumatoid factor, hepatitis panel, parasite blood smear
Hematology was consulted urgently for concerns of TTP, with hemolytic uremic syndrome (HUS) and pseudo-TMA as the other differentials. Peripheral smear showed pale RBCs, rare schistocytes, target cells, and hypersegmented neutrophils, steering away from TMA. PLASMIC score was 4 (low risk), ADAMTS13 level was sent, and empiric steroids were started. There was enough suspicion to consider TMA and initiation of therapeutic plasma exchange (TPE), but she declined it due to her religious beliefs. Further workup for macrocytic anemia yielded B12 level &lt;100 pg/mL and normal folate level, shifting suspicion towards pseudo-TMA by end of day 1 of hospitalization. She was started on intramuscular cyanocobalamin 1000 mcg daily along with iron, folic acid, and erythropoietin (EPO) supplementation. B12 deficiency was attributed to pernicious anemia with positive intrinsic factor blocking and antinuclear antibodies. ADAMTS13 activity returned normal (69%) ruling out TTP.
By day 6, Hgb and retic count improved to 7.6 g/dL and 44.4%, respectively. Steroids were discontinued, and she was discharged on sublingual B12 and weekly EPO injections. On hematology follow-up three weeks later, Hgb improved to 11 g/dL, and EPO was discontinued.
Discussion: Anemia, thrombocytopenia, elevated LDH and indirect bilirubin, low haptoglobin, and schistocytes on smear typically suggest TMA. Untreated TTP has a 90% mortality rate, necessitating immediate treatment. The PLASMIC score helps identify patients who would benefit from TPE while awaiting a confirmatory diagnosis. However, the fear of high mortality from untreated TTP can lead to anchoring bias and unnecessary use of potentially harmful and costly therapies. Providing cost-effective care while minimizing mortality requires early evaluation and exclusion of other potential diagnoses.
Differentiating between pseudo-TMA and TTP remains challenging, but higher median platelet count, lower retic count, higher MCV, leukopenia, and hypersegmented neutrophils often characterize pseudo-TMA as opposed to TTP. These findings along with a low PLASMIC score in our patient, suggested a higher likelihood of pseudo-TMA. Early detection of low B12 levels led to a timely diagnosis and definitive treatment with cyanocobalamin and supportive therapies, resulting in rapid recovery. Steroids, although empiric for TTP, have shown some benefit in enhancing B12 absorption in patients with pernicious anemia. Early recognition and treatment of B12 deficiency are especially crucial in Jehovah's Witnesses who cannot accept transfusions, complicating empiric treatment with TPE.
Conclusion: While initial management of hematologic abnormalities suggestive of TMA may follow protocols for life-threatening conditions like TTP, clinicians must remain vigilant for alternative diagnoses such as B12 deficiency-associated pseudo-TMA. Comprehensive laboratory workup and careful interpretation of peripheral smear are essential for appropriate management strategies and cost-effective patient care.