WHEN VITAMIN DEFICIENCY MIMICS THROMBOTIC THROMBOCYTOPENIC PURPURA

Abstract

To the Editor: Thrombotic thrombocytopenic purpura (TTP) is appropriately suspected in patients who have had acute peripheral thrombocytopenia and microangiopathic hemolysis associated with fluctuating neurological symptoms, renal failure, and fever. There is no criterion standard for diagnosis; a deficiency of von Willebrand factor–cleaving protease activity is found in up to 70% of patients with TTP, but its specificity for TTP diagnosis remains unknown.1 Once the diagnosis of TTP is seriously considered, urgent plasma exchange or infusion is indicated.1,2 We present a patient who was admitted into our intensive care unit for plasma exchange due to clinical and biological abnormalities suggesting a TTP. A 70-year-old man with no medical history of falls was admitted to the emergency department because of a fall in the street. On admission, the patient was confused, with no focal neurological deficit. All deep-tendon reflexes were absent, with flexor plantar responses. Blood pressure was about 100/50 mmHg, pulse was 70 beats per minute with a regular rhythm, and body temperature was 38°C. Significant laboratory findings included anemia, with a hemoglobin level of 4.5 g/dL and a mean corpuscular volume of 100 μm3, without leucopenia or thrombocytopenia. In addition, high total bilirubinemia (8.4 mg/dL), conjugated bilirubinemia (1.5 mg/dL), and serum lactic dehydrogenase (15,300 UI/L) were found. Serum iron and serum ferritin levels were normal. After a transfusion of three red blood cell units, the patient was transferred to a medical ward. Over the following 4 days, the patient remained confused, with fluctuating episodes of disorientation and agitation. Cerebral computed tomographic scan and electroencephalogram were found to be normal. No obvious source of infection was found. A few cutaneous purpuric and ecchymotic lesions progressively appeared, confined to the pressure points and the venous puncture sites. Over the 4 days, biological data showed a decrease in platelet count from 171 × 109/L to 41 × 109/L, the persistence of hemolytic anemia with a hemoglobin level of 7.5 g/dL associated with marked reduction of serum haptoglobin (below 0.008 g/L), and a lactic dehydrogenase of about 30,000 UI/L, although schistocytosis was not found. Moreover, acute renal insufficiency appeared with an increase of serum creatinine from 1.3 to 2.3 mg/dL, associated with microscopic hematuria. Because the association between thrombocytopenic purpura, massive hemolytic anemia, renal insufficiency, and fluctuating neurological disorders could suggest TTP, the patient was transferred to the intensive care unit to perform plasma exchange, but the macrocytic aspect of the red blood cells, the low reticulocyte count, and the absence of schizocytes on the peripheral blood film led to a bone marrow examination, which showed megaloblastic changes. So, it was hypothesized that a vitamin deficiency could have induced the symptoms and signs of this toothless old patient with a body mass index of 16. A low level of plasma ascorbic acid (2 mg/L; normal values: 7–12 mg/L) confirmed the diagnosis of scurvy and explained at least the ecchymotic and purpuric lesions. The serum vitamin B12 concentration of 140 ng/L (normal values: 211–911 ng/L) but a normal serum folic acid concentration (6.8 μg/l; normal values upper 5.3 μg/L) explained the megaloblastic anemia and hemolysis, thrombocytopenia, and neurological symptoms. Hyperhomocysteinemia (0.96 μg/L; normal values <0.11 μg/L) was found, as one would expect. Finally, his daughter revealed several days later that her father had been a vegan for at least 30 years and that his wife had committed suicide 6 months previously, which could account for depressive syndrome and accentuation of his diet. Balanced meals and an oral vitamin supplement quickly corrected renal insufficiency, thrombocytopenia, hemolysis with a reticulocytic crisis, and the clinical symptoms.3 An ophthalmic examination showed a cataract in each eye due to vitamin B12 deficiency. Gastroscopy was normal, and abdominal ultrasonographic study and different serum tumor markers did not provide evidence of malignancy. Improvement in his mental state was significant, with a Mini-Mental State Examination score of 20 of 30 after a few days. Vitamin B12 and folate deficiencies mimicking acute leukemia or the syndrome of hemolysis, elevated liver enzymes, and low platelets have been reported.4,5 The interesting part of this observation was that, when associated with ascorbic acid deficit leading to ecchymotic and purpuric lesions, these vitamin deficits may mimic TTP. Clinicians must be aware of unusual clinical presentations of TTP in patients with multiple vitamin deprivation. Noninstitutionalized elderly subjects, socially isolated patients, and food faddists are probably a high-risk population for such manifestations. Financial Disclosure: The authors declare that they received no financial support for this manuscript. Author Contributions: Bernard Tardy and Sandrine Bayle: acquisition of subjects and data and preparation of manuscript. Yves Page and Eric Diconne: acquisition of data. Fabrice Zeni and Jean C. Bertrand: preparation of manuscript. Sponsors' Role: None.