Jean-Marie Michot

Hemolysis and schistocytosis in the emergency department: consider pseudothrombotic microangiopathy related to vitamin B12 deficiency

BACKGROUND Hemolytic anemia with thrombocytopenia and schistocytosis is suggestive of thrombotic thrombocytopenic purpura (TTP). However, these features can occur in the context of vitamin B12 deficiency. AIM To identify simple means of distinguishing between TTP and pseudothrombotic microangiopathies related to vitamin B12 deficiency (pseudo-TMA) at the bedside. DESIGN AND METHODS Retrospective study of patients with pseudo-TMA compared with patients with TTP. The patients with pseudo-TMA were further compared with other cases of cobalamin deficiency, in order to detect factors associated with microangiopathic hemolysis during vitamin B12 deprivation. RESULTS Seven patients with pseudo-TMA were compared with six patients with TTP. The pseudo-TMA patients had higher median lactate dehydrogenase (LDH) levels (7310 vs. 1460 IU/l, P = 0.01), a higher platelet count (73 vs.12.5 × 10(9)/l, P = 0.0023), a lower reticulocyte count (13.1 vs. 265.5 × 10(9)/l, P = 0.0012) and a lower neutrophil count (1.3 vs. 5.1 × 10(9)/l, P = 0.0023). When compared with 21 patients with vitamin B12 deficiency and anemia (but no schistocytosis), the pseudo-TMA patients were more likely to present with pernicious anemia [7 out of 21 (33.3%) vs. 5 out of 7 (71.4%), respectively] and had lower vitamin B12 levels (105 vs. 45 µmol/l, respectively). Vitamin supplementation led to hematological improvements in all pseudo-TMA patients. CONCLUSION In a context of mechanical hemolysis with thrombocytopenia in a patient admitted to the emergency department, very high LDH levels and a low reticulocyte count are strongly suggestive of pseudo-TMA and should prompt the physician to screen for cobalamin deficiency.

Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases.

Immunosuppressive therapy may trigger hepatitis B virus (HBV) reactivation for increased morbidity and mortality. We aimed to describe HBV reactivation in patients receiving treatment for immune‐mediated inflammatory diseases (IMIDs) and to evaluate a predefined algorithm for its prevention.

Immunohematologic tolerance of chronic transfusion exchanges with erythrocytapheresis in sickle cell disease

Sickle cell disease (SCD) has become a major public health issue. Hydroxyurea and red blood cell (RBC) transfusion are the cornerstone treatments. Erythrocytapheresis (ECP) is an automated method for transfusion exchange. Given that ECP requires more blood than conventional transfusion, there is concern about alloimmunization and hemolytic transfusion reactions. We evaluate the incidence of hemolytic transfusion reactions and alloimmunization rates in patients receiving conventional blood transfusions and in patients participating in long‐term blood exchange programs with ECP.

Adenosine deaminase is a useful biomarker to diagnose pleural tuberculosis in low to medium prevalence settings

Adenosine deaminase (ADA) activity measurement in pleural fluid is a relevant test to diagnose pleural tuberculosis (pTB) in high tuberculosis prevalence settings. We investigated the diagnostic utility of pleural ADA using a retrospective analysis of patients admitted with newly diagnosed pleural effusion without identified etiology between 2001 and 2008 in Paris suburb, a low to medium tuberculosis prevalence area. 104 adults (mean age 55 years; 34 with pTB, 70 with other diagnoses) were analyzed. Median follow-up was 15.6 months. Mean [interquartile range] pleural ADA was 119 U/L [IQR: 83-143] in pTB and 24 U/L [IQR: 15-31] in non-tuberculous effusions (P<0.001). With an optimal pleural ADA cut-off value of 41.5 U/L for pTB diagnosis, sensitivity and specificity were 97.1% and 92.9%, while positive and negative predictive values were 86.8% and 98.5%, respectively. We conclude that pleural ADA activity could be integrated in the diagnostic procedures of pTB in low to medium tuberculosis prevalence settings.

Haemophagocytic histiocyte in a peripheral blood film

A 79-year-old woman presented with weakness. Her full blood count showed haemoglobin concentration 100 g/l, platelets 53 9 10/l, leucocytes 6 5 9 10/l, neutrophils 3 3 9 10/l and myeloblasts 0 8 9 10/l. Bone marrow aspiration showed pronounced dysgranulopoiesis and 24% myeloblasts, leading to the diagnosis of acute myeloid leukaemia. Cytogenetic analysis showed t(8;21)(q22;q22). Treatment with azacitidine was started (75 mg/m2 per day for 7 d). Eleven days later, the patient developed severe pneumonia. Concomitantly, microscopic examination of a blood film revealed a single haemophagocytic histiocyte (image). No other histiocytes were found on five additional films from the same blood specimen. This finding led to additional laboratory tests, which showed a reduced prothrombin index and fibrinogen concentration (58% and 1 6 g/l, respectively) while ferritin and lactate dehydrogenase were greatly increased, to 64 300 lg/l (normal 25–350) and 2962 iu/l (10 times the normal level), respectively. A diagnosis of haemophagocytic lymphohistiocytosis (HLH) was made. Despite the early introduction of broad-spectrum antibiotic therapy, the patient died 21 d after the start of azacitidine treatment. Haemophagocytic lymphohistiocytosis is characterized by a cytokine storm with activation of lymphocytes and excessive and inappropriate activation of macrophages, which engulf haemopoietic cells and their progeny. This hyperinflammatory condition has a high mortality rate (~50%) and has been mostly associated with three disease groups: cancer, infection and autoimmune disorders. Myeloid malignancies are rarely associated with HLH. Therefore in the present case we hypothesize that HLH was most likely the result of the inappropriate immune response triggered by the pneumonia rather than the malignant disease. Cytological evidence of haemophagocytosis is usually found in bone marrow films or in other organ biopsies (lymph nodes, liver, skin etc.). The observation of haemophagocytic histiocytes in a peripheral blood film is uncommon. To our knowledge, fewer than 10 instances have been reported. Most of these cases were fatal and often related to severe respiratory infections.