Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

Abstract

We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications.

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.…”

“…Other causes include alcohol excess, hypothyroidism, liver disease, myelodysplastic syndrome and the fish tapeworm Diphyllobothrium. 3,7,8,11,12,14 The most common reason for cobalamin deficiency is pernicious anemia, a slow acting autoimmune mechanism disrupting the IF-Cobalamin absorption. 2,3,11,12,14 Bariatric surgery associated parietal cell removal or removal of the terminal ileum mimics this with surgical suddenness.…”

“…3,7,11,12 Deficiency impairs DNA synthesis delaying migration of the DNA replication fork and annealing DNA fragments of the lagging strand, arresting maturation of hematopoietic cell precursors. 6,8,9,11,16 This creates ineffective erythropoiesis by intramedullary apoptosis in the marrow, but intravascularly, the asynchronous maturation of nucleus and cytoplasm create large erythrocytes with rigid but fragile cell membranes, 3,6,10,11,13,14,15,16 prone to hemolysis with sheering stress (Figure 2). Homocysteine accumulation causes that stress with endothelial damage, vasoconstriction, activation of the coagulation system and platelet aggregation.…”

“…Thrombocytopenia occurs from platelet aggregation, with the resultant debris eventually causing organ ischemia leading to dysfunction and failure, especially in the brain, heart, kidney and gastrointestinal system. 8,12,13 This progression occurs most often in TTP but can also be seen in pseudo-TTP if severe enough. The etiologies are different, with TTP initiated by a decrease in the ADAMTS-13 activity, 3,5,6,7,8,9 while pseudo-TTP combines the fragility of erythrocytes enlarged by ineffective erythropoiesis with homocysteine induced endothelial damage, vasoconstriction, platelet aggregation and coagulation activation.…”

“…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.…”