Pablo Bartolucci

Recommandations pratiques de prise en charge de la drépanocytose de l’adulte

Sickle cell disease is a systemic disease that can potentially involve all organs. As the prevalence of patients with sickle cell disease increases gradually in France, every physician can be potentially involved in the care of these patients. Complications of sickle cell disease can be acute or chronic. Pain is the main symptom and should be treated quickly and aggressively. Acute chest syndrome is the leading cause of acute death and must be prevented, detected, and treated without delay. Chronic complications are one of the main concerns in adults and should be identified as early as possible in order to prevent sequels. Many organs can be involved, including the bones, kidneys, eyes, lungs... The indications for a specific treatment (blood transfusion or hydroxyurea) should be discussed. Health care should be carefully organized to allow both a regular follow-up near the living place and access to specialized departments. We present in this article the French guidelines for the sickle cell disease management in adulthood.

Delayed hemolytic transfusion reaction in adult sickle-cell disease: presentations, outcomes, and treatments of 99 referral center episodes.

Delayed hemolytic transfusion reaction (DHTR) is one of the most feared complications of sickle‐cell disease (SCD). We retrospectively analyzed the clinical and biological features, treatments and outcomes of 99 DHTRs occurring in 69 referral center patients over 12 years. The first clinical signs appeared a median of 9.4 [IQR, 3–22] days after the triggering transfusion (TT). The most frequent DHTR‐related clinical manifestation was dark urine/hemoglobinuria (94%). Most patients (89%) had a painful vaso‐occlusive crisis and 50% developed a secondary acute chest syndrome (ACS). The median [IQR] hemoglobin‐concentration nadir was 5.5 [4.5–6.3] g/dL and LDH peak was 1335 [798–2086] IU/L. Overall mortality was 6%. None of the patients had been receiving chronic transfusions. Among these DHTRs, 61% were developed in previously immunized patients, 28% in patients with prior DHTR. Among Abs detected after the TT in 62% of the episodes, half are classically considered potentially harmful. No association could be established between clinical severity and immunohematological profile and/or the type and specificity of Abs detected after the TT. Management consisted of supportive care alone (53%) or with adjunctive measures (47%), including recombinant erythropoietin and sometimes rituximab and/or immunosuppressants. Additional transfusions were either ineffective or worsened hemolysis. In some cases, severe intravascular hemolysis can be likely responsible for the vascular reaction and high rates of ACS, pulmonary hypertension and (multi)organ failure. In conclusion, clinicians and patients must recognize early DHTR signs to avoid additional transfusions. For patients with a history of RBC immunization or DHTR, transfusion indications should be restricted. Am. J. Hematol. 91:989–994, 2016.

The use of rituximab to prevent severe delayed haemolytic transfusion reaction in immunized patients with sickle cell disease

Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD).

Sickle‐cell disease stroke throughout life: A retrospective study in an adult referral center

Strokes are one of the most severe complications of sickle‐cell disease. Most studies have been restricted to children with sickle‐cell disease. To better understand the characteristics and follow‐up of strokes occurring from childhood to adulthood, we undertook a retrospective cohort study of 69 stroke patients among the 2,875 patients consulting at the French Adult Sickle‐Cell Disease Referral Center. Between 1970 and 2008, they had experienced 104 strokes: 80 ischemic, 22 hemorrhagic, and 2 intracranial sinus thromboses. Coma and/or fatal outcomes underscored the severity of strokes in sickle‐cell disease patients. Hemorrhagic strokes occurred mostly in adults and carried a higher risk of death than ischemic stroke. The mechanisms underlying sickle‐cell disease associated strokes were reevaluated and etiologies were determined for first stroke and recurrences, in childhood and adulthood. Sickle‐cell disease vasculopathy concerned only SS patients and remains their most frequent stroke etiology. Cardioembolism, vaso‐occlusive crisis and triggering factors were other etiologies identified in adults. Recurrences occurred in 19 SS patients only after a first ischemic stroke. SC patients strokes occurred in adulthood and were associated with cardiovascular risk factors. Our findings provide novel information about cerebrovascular pathologies throughout the lives of sickle‐cell disease patients and suggest the need for different diagnostic and therapeutic management approaches in those different settings. Am. J. Hematol. 89:267–272, 2014.

A diagnostic nomogram for delayed hemolytic transfusion reaction in sickle cell disease.

Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso‐occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within 1 week following an index transfusion and repeated within 2 months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%), and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post‐transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. Am. J. Hematol. 91:1181–1184, 2016.

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention, diagnosis, treatment

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.

Low-impact laparoscopic cholecystectomy is associated with decreased postoperative morbidity in patients with sickle cell disease

BackgroundLaparoscopic cholecystectomy (LC) is one of the most frequent surgeries performed in patients with sickle cell disease (SCD). LC in SCD patients is associated with a particularly high postoperative morbidity. The aim of the present study is to assess the safety and feasibility of cholecystectomy performed by mini-laparoscopy with low- and stable-pressure pneumoperitoneum (MLCu2009+u2009LSPP) and to compare the rate of postoperative SCD-related morbidity with standard LC.MethodsThirty-five consecutive SCD patients admitted between November 2015 and March 2017 for cholelithiasis requiring surgery were compared with an historical cohort of 126 SCD patients who underwent LC for the same indication. Operative variables, postoperative outcomes, patient and surgeon satisfaction, and costs were evaluated.ResultsMLCu2009+u2009LSPP exhibited a mean operative time comparable to LC (pu2009=u20090.169). Operative blood loss was significantly reduced in the MLCu2009+u2009LSPP group, and the suction device was rarely used (pu2009=u20090.036). SCD-related morbidity (including acute chest syndrome) was significantly higher in the LC group compared with the MLCu2009+u2009LSPP group (18.3 vs. 2.9%; pu2009=u20090.029). The mean times to resume ambulation (pu2009=u20090.018) and regular diet (pu2009=u20090.045) were significantly reduced in the MLCu2009+u2009LSPP group. The mean incision length (all trocars combined) was 28.22xa0mm for MLCu2009+u2009LSPP and 49.64xa0mm for LC patients (pu2009<u20090.0001). Multivariate regression analysis demonstrated that the only significant predictor of postoperative SCD-related morbidity was the surgical approach (odds ratio: 9.24). Patient and surgeon satisfaction were very high for MLCu2009+u2009LSPP. The mean total cost per patient (surgery and hospitalization) was not different between groups (pu2009=u20090.084).ConclusionMLCu2009+u2009LSPP in SCD patients appears to be safe and feasible. Compared with LC, MLCu2009+u2009LSPP in SCD patients is associated with a significantly reduced incidence of postoperative SCD-related morbidity and more rapid ambulation and return to regular diet without increasing the total costs per patient.

Anti-HI can cause a severe delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease patients.

Delayed hemolytic transfusion reaction (DHTR) is a life‐threatening condition in sickle cell disease (SCD) patients that is frequently complicated by hyperhemolysis. Antibodies resulting from antigen disparity between donors of European ancestry and patients of African ancestry are common, but situations involving antibodies not classically of clinical significance are also encountered. Anti‐HI is generally considered to be an innocuous naturally occurring antibody.

Reversible kidney iron accumulation in a patient with sickle cell disease treated with hydroxyurea.

In patients with homozygous sickle cell disease (SCD), albuminuria and hyperfiltration are associated with intensity of hemolysis [1,2], suggesting that a chronic hemolysis-induced vasculopathy may play a role in the development of sickle cell nephropathy (SCN) [1]. Magnetic resonance imaging (MRI) has revealed accumulation of iron in the kidney parenchyma [3,4] and renal biopsy data have demonstrated abundant hemosiderin deposits in proximal tubular epithelial cells in patients with SCD [1]. The optimal therapeutic management of SCN remains unclear, but we recently showed that hydroxyurea (HU), the cornerstone of SCD treatment, may decrease albuminuria by reducing hemolysis [5]. We report here the case of a 32-year-old man with SCD, who displayed a total disappearance of MRI-proven kidney iron overload and a significant decrease in albuminuria after a 16-month course of HU treatment. A 32-year-old African man was referred to our center, for the evaluation of homozygous SCD disease. His medical history included bouts of malaria, and resolved hepatitis B virus infection. In the preceding two years, he reported two vaso-occlusive crisis (VOC) episodes and two acute chest syndromes (ACS) requiring hospitalization. He had not previously been included in a blood exchange transfusion protocol and he was not taking any iron-chelating agent or antihypertensive therapy. On admission, his clinical examination was unremarkable and his blood pressure was 115/75 mmHg. The laboratory findings are summarized in Supporting Information Table 1. Marked anemia was associated with a high rate of hemolysis, as highlighted by elevated lactate dehydrogenase (LDH) (1144 U/L), total bilirubin (140 mmol/L), and aspartate aminotransferase (AST) Fig. 1. Coronal T2*-weighted MRI of the kidneys, with a weak cortical signal on the first MRI scan (A) suggestive of iron deposition. The cortical signal is normal on the second examination (B) probably due to the clearance of iron deposits from the cortex. The medullary signal was similar on the two MRI examinations.

A clinical risk score for pulmonary artery thrombosis during acute chest syndrome in adult patients with sickle cell disease.

Pulmonary artery thrombosis (PAT) is involved in lung vascular dysfunction during acute chest syndrome (ACS) complicating sickle cell disease (SCD). No clinical score is available to identify patients eligible for multi‐detector computed tomography (MDCT) angiography during ACS. This retrospective study aimed to develop a risk score for PAT during ACS (PAT‐ACS risk score). Patients with SCD were investigated by MDCT during ACS. A logistic regression was performed to determine independent risks factors for PAT and to build the PAT‐ACS risk score. A total of 43 episodes (11·9%) of PAT were diagnosed in 361 episodes of ACS. Multivariate analysis identified four risk factors, which were included in the PAT‐ACS risk score: a baseline haemoglobin >82 g/l, the lack of a triggering factor for ACS, a platelet count >440 × 109/l and a PaCO2 <38 mmHg at ACS diagnosis. The area under the receiver operating characteristic curve for the PAT‐ACS risk score was 0·74 (95% confidence interval [CI] 0·69–0·79) and differed from that of the revised Geneva score (0·63 (95% CI 0·58–0·69); P = 0·04). The negative predictive value of a PAT‐ACS risk score ≥2 was 94%. In conclusion, we propose a simple clinical risk score to identify SCD patients at high risk of PAT during ACS.