Scientific letter
Pseudo thrombotic microangiopathy secondary to vitamin B12 deficiency
Seudomicroangiopatía trombótica secundaria a déficit de vitamina B12
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With this clinical case of a pseudo thrombotic microangiopathy due to vitamin B12 deficiency, we aimed to show a different diagnostic challenge with a successful result and a simple treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This article describes the clinical case of 55-year-old men with type 2 diabetes mellitus controlled with metformin and chronic hepatic disease of alcoholic aetiology, with known oesophageal varices. He was admitted to the emergency department for weight loss, asthenia and jaundice. He had a previous analytical study 5-days-old with a haemoglobin value of 7.1<span class="elsevierStyleHsp" style=""></span>g/dL; the previous known value was 13<span class="elsevierStyleHsp" style=""></span>g/dL, 6 months before. At physical examination he was conscious, with correct temporal space orientation, with no flapping, but lethargic. Mucous membranes were pale and hydrated; sclerae was icteric. Abdomen was soft and tender, not painful at palpation, without ascites or organomegalies. Blood pressure was 134/60<span class="elsevierStyleHsp" style=""></span>mmHg, heart rate 70 beats per minute (bpm), with no fever.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Laboratory workup showed anaemia with haemoglobin of 6.3<span class="elsevierStyleHsp" style=""></span>g/dL, normocytic, haematocrit of 21.9%, mean corpuscular volume (MCV) of 92.4<span class="elsevierStyleHsp" style=""></span>fL, leukopenia of 2.42/L and thrombocytopenia (44,000/L platelets). Reticulocyte count was normal (1.51%), with a reticulocyte production index of 0.37%. The C reactive protein (CRP) value was 8.5<span class="elsevierStyleHsp" style=""></span>mg/L (<3<span class="elsevierStyleHsp" style=""></span>mg/L). He had total bilirubin of 3.12<span class="elsevierStyleHsp" style=""></span>mg/dL (<1.20<span class="elsevierStyleHsp" style=""></span>mg/dL), with no relevant change on other liver enzymes. The lactate dehydrogenase (LDH) value was high of 5076<span class="elsevierStyleHsp" style=""></span>U/L (135–225<span class="elsevierStyleHsp" style=""></span>U/L); vitamin B12 dosing was low (<83<span class="elsevierStyleHsp" style=""></span>pg/mL), as well as haptoglobin (<8<span class="elsevierStyleHsp" style=""></span>mg/dL); direct Coombs test was negative. Prothrombin time (PT) was 17.1<span class="elsevierStyleHsp" style=""></span>s (10.4–14.3<span class="elsevierStyleHsp" style=""></span>s) and activated partial thromboplastin time (aPTT) 38.8<span class="elsevierStyleHsp" style=""></span>s (24.4–36.4<span class="elsevierStyleHsp" style=""></span>s). Renal function, potassium and sodium were normal. The peripheral blood smear showed anisocytes, numerous schistocytes and macro-ovalocytes. He was transfused with two units of packed red cells and started on proton pump inhibitor. He underwent an upper gastrointestinal tract endoscopy, that showed already known oesophageal varices without signs of active bleeding, and an abdominal echography that suggested chronic hepatopathy and splenomegaly.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was first transferred to an intermediate care unit, where he improved his neurological status as well as his anaemia and thrombocytopenia only with cyanocobalamin supplementation and general care support. He was transferred to the infirmary 3 days later. He was discharged after 11 days in the hospital, with intramuscular cyanocobalamin and folic acid supplementation. ADAMST13 dosing came back normal (50%) 5 days later. His discharge blood work had improved. Although it was a difficult decision, the patient wasn’t started immediately into plasma exchange, since he remained haemodynamically stable and the vitamin B12 dosing came back fast and was very low. He continued to improve steadily under its supplementation. This is a debatable choice given the high mortality rate of TTP without plasmapheresis (90%).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The differential diagnosis of this case was challenging. The first diagnostic hypothesis was acute decompensation of chronic hepatic disease due to upper gastrointestinal bleeding. Against it was the absence of evidence of bleeding and the presence of haemolysis. The second one was thrombotic microangiopathy (TMA); supporting this were the laboratory findings of non-immune haemolytic anaemia: elevated LDH, hyperbilirubinemia due to elevation of the indirect fraction, a negative Coombs test, low haptoglobin, the presence of numerous schistocyte in the peripheral blood smear; and thrombocytopenia. This disease can have a primary aetiology, which includes thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> TTP seemed more likely, considering normal renal function and the neurological changes. Besides these, vitamin B12 deficiency can cause a syndrome named pseudo-TMA,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3–5</span></a> which fitted this case. Patients with severe cobalamin deficiency may present with symptoms that mimic TMA syndromes, which is a clinical manifestation of cobalamin deficiency is 2.5% of cases.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3</span></a> It does not respond to plasma exchange.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Differentiating pseudo-TTP from TTP is challenging, given the remarkable difference in treatment and mortality. Small series of cases report that patients with pseudo-PTT are usually older, have higher levels of LDH (>2500<span class="elsevierStyleHsp" style=""></span>UI/L) and inappropriate reticulocytopenia.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4,5</span></a> Once more, a risk was taken not starting plasmapheresis empirically; this technique also has its risks, with complications (catheter related, plasma reactions) in up to 30%.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> After investigation, the patient had two possible explanations for the vitamin B12 deficiency: long-term use of metformin and positivity for both autoantibodies for intrinsic factor and for autoantibodies for parietal cells. A diagnosis of pernicious anaemia was made. He remains stable under vitamin supplementation in external follow-up.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors don’t have any conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pernicious anemia associated cobalamin deficiency and thrombotic microangiopathy: case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. 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Martin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12878-015-0036-2" "Revista" => array:5 [ "tituloSerie" => "BMC Hematol" "fecha" => "2015" "volumen" => "15" "paginaInicial" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26634125" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.N. Tran" 1 => "M.H. 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