Neglect‐induced pseudo‐thrombotic thrombocytopenic purpura due to vitamin B12 deficiency

Abstract

Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect.

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.…”

“…11,12 Dietary sources of cobalamin are of animal origin: meat, eggs, and dairy. 11,12,14,15 It is released from food by gastric secretions in the stomach and pancreatic secretions in the duodenum. It binds to intrinsic factor, secreted from gastric parietal cells, and this B12-IF complex is internalized by the cubam receptor in the terminal ileum for release into the plasma.…”

“…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.…”

“…3,7,8,11,12,14 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. 3,11 Cobalamin is a required cofactor in two biochemical reactions: the conversion of methylmalonyl CoA to succinyl CoA and the methylation of homocysteine to methionine.…”

“…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.…”