Pernicious Anemia Associated Cobalamin Deficiency and Thrombotic Microangiopathy: Case Report and Review of the Literature

Abstract

A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam. Presence of hemolytic anemia, schistocytosis, thrombocytopenia, and elevated lactate dehydrogenase (LDH) was suggestive of thrombotic thrombocytopenic purpura (TTP). However, presence of leukopenia, macrocytes, and an inadequate reticulocyte response to the degree of anemia served as initial clues to an alternative diagnosis. Two and one units of packed red blood cells were transfused on day 1 and day 3, respectively. In addition, one unit of platelets was transfused on day 2. Daily therapeutic plasma exchange (TPE) was initiated and continued until ADAMTS-13 result ruled out TTP. A low cobalamin (vitamin B12) level was evident at initial laboratory work-up and subsequent testing revealed positive intrinsic factor-blocking antibodies supporting a diagnosis of pernicious anemia with severe cobalamin deficiency. Hematological improvement was observed following vitamin B12 supplementation. The patient was discharged and markedly improved on day 9 with outpatient follow-up for cobalamin supplementation.

Cobalamin Deficient Thrombotic Microangiopathy: a case of TTP or Pseudo-TTP

“…3,5,6,8,9,14 It is caused by a severe deficiency of ADAMTS-13 metalloproteinase, which cleaves ultra-large von Willebrand factor (ulvWF) multimers. 3,5,6,7,8,9,10,15 In a deficiency of < 10% of this gamma immunoglobulin, ulvWF strings form in the microcirculation encouraging platelet deposition. This results in thrombocytopenia and obstruction of microvasculature with resultant damage to erythrocytes.…”

“…This results in thrombocytopenia and obstruction of microvasculature with resultant damage to erythrocytes. 3,4,5,6,9,10 TTP occurs in one of two ways.…”

“…1,2,3,4 TMAs are rare, with an estimated incidence of 4 per 1 million, 1,5,6 but have a mortality rate of 10-20%. 1 Hemolytic Uremic Syndrome, cancer, HIV, hemopoetic stem cell transplant, connective tissue disorders and medications, like oxymorphone, Quinine, calcinuerin inhibitors and antineoplastic agents, can result in TMA.…”

“…1 Hemolytic Uremic Syndrome, cancer, HIV, hemopoetic stem cell transplant, connective tissue disorders and medications, like oxymorphone, Quinine, calcinuerin inhibitors and antineoplastic agents, can result in TMA. 3,5,7,8 The most common TMA is thrombotic thrombocytopenic purpura (TTP), or Moschowitz disease, with 2-3 individuals per million incidence. 5 Acute TTP episodes, whether in congenital or acquired forms, have a high mortality rate, and the treatment is invasive and comes with considerable risk.…”

“…5 Acute TTP episodes, whether in congenital or acquired forms, have a high mortality rate, and the treatment is invasive and comes with considerable risk. 3,7,9,10 Cobalamin (Vitamin B12) deficiency has a prevalence of 4-15%, which is higher in the elderly. 1,6,9,11,12 Most symptomatology is mild, but lifethreatening manifestations can occur.…”