Vitamin B12 Deficiency Mimicking Thrombotic Thrombocytopenic Purpura
Bob Ly, DO, and Jhoanna Santos, MD
Skagit Regional Health, Mount Vernon, Washington
Ly B, Santos J. Vitamin B12 deficiency mimicking thrombotic thrombocytopenic purpura. Consultant. 2017;57(10):618-619.
Severe vitamin B12 deficiency can lead to pseudothrombotic microangiopathy, which can present similarly to the microangiopathic hemolytic anemias, particularly thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation.1 Recognition of the clinical and laboratory features of pseudothrombotic microangiopathy is important, since management with vitamin B12 replacement is simple and effective.
Presentation. A 53-year-old man with a past medical history significant for coronary artery disease presented with worsening weakness and exertional dyspnea over a period of 1 week. The patient also reported paresthesia in his hands and feet bilaterally but otherwise denied chest pain, fever, chills, night sweats, nausea, vomiting, or diarrhea. Prior to presentation, he had not been on any medication and was without routine medical care. He denied tobacco or illicit drug use, and he consumed alcohol very sparingly.
Physical examination. His vital signs were as follows: temperature, 36.9°C; heart rate, 86 beats/min; blood pressure, 151/100 mm Hg; respiratory rate, 17 breaths/min; and oxygen saturation, 99% on room air. He was not in any acute distress. Cardiovascular examination revealed an irregularly irregular rhythm without murmur. Lung sounds were clear bilaterally. Neurologic examination showed grossly intact cranial nerves II through XII, with 5/5 motor strength throughout and normal deep tendon reflexes.
Diagnostic tests. Pertinent laboratory data on admission included the following values: hemoglobin, 9.5 g/dL; hematocrit, 27.8%; mean corpuscular volume, 93.9 µm3; white blood cell (WBC) count, 3000/µL; platelet count, 62 × 103/µL; total bilirubin, 2.6 mg/dL; aspartate aminotransferase, 60 U/L; alanine aminotransferase, 29 U/L; and alkaline phosphatase, 46 U/L.
Further studies in the workup for pancytopenia yielded the following values: serum iron, 98 µg/dL; iron binding capacity, 281 µg/dL; iron saturation, 35%; ferritin, 219 ng/mL; folate, 17.5 ng/mL; vitamin B12, less than 31 pg/mL; lactate dehydrogenase (LDH), 2520 U/L; and haptoglobin, less than 10 mg/dL.
Schistocytes, polychromasia, and few platelets were identified on a peripheral smear (Figure).
The hematology team was consulted to assess for possible TTP, given the findings of schistocytes on the peripheral smear and the elevated LDH level. A diagnosis of pseudothrombotic microangiopathy was suspected from the severe vitamin B12 deficiency. Additional results of investigational studies confirming vitamin B12 deficiency included elevated levels of methylmalonic acid (108.5 µmol/L) and homocysteine (> 250 µmol/L). To further evaluate for the etiology of the vitamin B12 deficiency and assess for pernicious anemia, an esophagogastroduodenoscopy with gastric pH measurements and gastric biopsy were performed, the results of which showed atrophic gastritis with a stomach pH between 6.5 and 7. Additional laboratory data confirming pernicious anemia included a positive intrinsic factor antibody test result (1.8 AU/mL).
Discussion. Severe vitamin B12 deficiency is most often caused by a loss of intrinsic factor due to autoimmune gastritis (“pernicious anemia”),2 as was the case with our patient. Vitamin B12 deficiency is frequent in the general population and can present with a wide range of hematologic manifestations including, but rarely, pseudothrombotic microangiopathy.
The ineffective erythropoiesis resulting from vitamin B12 deficiency leads to intramedullary hemolysis and the release of LDH, which is also seen in microangiopathic hemolytic anemias,2 complicating the differential diagnosis. Pseudothrombotic microangiopathy presents with hemolytic anemia, thrombocytopenia, and schistocytosis and accounts for approximately 2.4% of the hematologic disorders seen with vitamin B12 deficiency.3 As a result, patients with pseudothrombotic microangiopathy are usually misdiagnosed with TTP and may inadvertently receive invasive and aggressive diagnostic procedures and treatments such as bone marrow aspiration, corticosteroids, immunoglobulins, and plasmapheresis.3-7
Recognition by clinicians of the various hematologic manifestations seen with vitamin B12 deficiency can help avoid these invasive procedures and therapies. Patients with hematologic abnormalities including hemolysis, schistocytosis, and thrombocytopenia warrant evaluation for vitamin B12 deficiency. Marked elevations in LDH and a low reticulocyte count are suggestive of pseudothrombotic microangiopathy.8,9
Treatment with replacement parenteral or high-dose oral vitamin B12 is effective and often well tolerated without adverse effects.
Outcome of the case. The patient was started on replacement vitamin B12 therapy with daily 1000-µg intramuscular injections for 1 week followed by once weekly injections for 4 weeks, and then once monthly injections thereafter.
The patient was also started on an anticoagulation regimen for new-onset atrial fibrillation that was diagnosed at the time of his admission.
Notable laboratory test results at an outpatient follow-up visit 2 weeks after hospital discharge included a hemoglobin level of 11.2 g/dL, a hematocrit of 36.6%, a WBC count of 6900/µL, a platelet count of 253 × 103/µL, a total bilirubin level of 0.9 mg/dL, and an LDH level of 274 U/L. Follow-up at 6 months showed continued clinical and laboratory improvements, with a hemoglobin level of 13.6 g/dL, a hematocrit of 43.5%, a platelet count of 198 × 103/µL, and vitamin B12 level of 575 pg/mL.
- Tadakamalla AK, Talluri SK, Besur S. Pseudo-thrombotic thrombocytopenic purpura: a rare presentation of pernicious anemia. N Am J Med Sci. 2011;3(10):472-474.
- Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160.
- Andrès E, Affenberger S, Zimmer J, et al. Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency. Clin Lab Haematol. 2006;28(1):50-56.
- Tuten N, Bennett C, Babcock W. Thrombotic thrombocytopenic purpura or cobalamin deficiency? A case report and review. Clin Case Rep Rev. 2015;1(8):157-159.
- Malek A, Nasnas R. An unusual presentation of pseudothrombotic microangiopathy in a patient with autoimmune atrophic gastritis. Case Rep Hematol. 2016;2016:1087831.
- Khalil R, Naqvi S, Chastain V. Vitamin B12 deficiency as a cause of hemolytic anemia [abstract]. J Hosp Med. 2012;7(suppl 2). http://www.shmabstracts.com/abstract/vitamin-b12-deficiency-as-a-cause-of-hemolytic-anemia/. Accessed September 25, 2017.
- Andreadis P, Theodoridou S, Pasakiotou M, et al. Vitamin B12 deficiency and hemoglobin H disease early misdiagnosed as thrombotic thrombocytopenic purpura: a series of unfortunate events. Case Rep Hematol. 2015;2015:478151.
- Noël N, Maigné G, Tertian G, et al. Hemolysis and schistocytosis in the emergency department: consider pseudothrombotic microangiopathy related to vitamin B12 deficiency. QJM. 2013;106(111):1017-1022.
- Walter K, Vaughn J, Martin D. Therapeutic dilemma in the management of a patient with clinical picture of TTP and severe B12 deficiency. BMC Hematol. 2015;15:16.