Evaggelia Vetsiou

Haematoma caused by bone marrow aspiration and trephine biopsy

We report a case of a bone marrow aspiration and trephine biopsy (BMATB) associated haematoma in an 85-years old male without any predisposing risk factors. Six days after BMATB, he suffered from a massive thigh and buttock haematoma and a fall in haematocrit. It is important to know that BMATB can have complications aiding early recognition and therapy.

Total remission of severe immune thrombocytopenia after short term treatment with romiplostim.

Immune thrombocytopenia (ITP) in adults is an acquired chronic immune-mediated disorder defined by isolated thrombocytopenia. In recent years, an improved understanding of the pathophysiology of ITP has been achieved and it is now accepted that the disorder is due to increased platelet destruction and decreased platelet production from megakary-ocytes. Thrombopoietin (TPO)-receptor agonists (romiplostim and eltrombopag) are new therapeutic modalities in the treatment of ITP. Here we describe a case of an elderly patient with severe ITP who presented complete remission after short-term use of romiplostim (only 3 weekly doses). This finding is quite interesting as the TPO-receptor agonists are, so far, believed to rarely lead to off-treatment sustained remission. The common notion of long-term use of romiplostim could be reexamined in future studies. Furthermore, the short term treatment with romiplostim may reduce the cost and the risk of side effects.

Iron chelation therapy of transfusion-dependent β-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic?

The life expectancy of thalassemic patients has increased, and now approaches that of healthy individuals, thanks to improved treatment regimens. However, pregnancy in women with β-Thalassemia Μajor remains a challenging condition. Recent advances in managing this haemoglobinopathy offer the potential for safe pregnancies with favorable outcome. However, clinical data regarding the use of chelation therapy during pregnancy are limited, and it is unclear whether these agents impose any risk to the developing fetus. Successful pregnancies following unintentional treatment with deferoxamine or deferasirox have rarely been reported. Generally, chelators are not recommended during pregnancy. Regarding the new oral chelators, data on fetotoxicity are lacking. In the present study, we describe the evolution and successful outcome of nine pregnancies in six Greek thalassemic women who received deferasirox inadvertently during early pregnancy, and review the literature regarding fetal anomalies due to chelators. Use of chelation before embarking upon a non-programmed pregnancy remains a difficult and unresolved question. In our study, chelation treatment during pregnancy did not prevent the delivery of healthy children. Nonetheless, the use of deferasirox is contraindicated in pregnant women, based on the product label. Deferasirox should only be used during pregnancy if the potential benefit outweighs the potential fetal risk.

Nephrolithiasis in beta thalassemia major patients treated with deferasirox: an advent or an adverse event? A single Greek center experience

Dear Editor, Thalassemia major (TM) is characterized by grossly defective synthesis of hemoglobin A and impaired red blood cells (RBC). Affected individuals need repeated blood transfusions, while shortened RBC life span and iron overload cause functional abnormalities in various organs. Iron chelation therapy is considered mandatory in order to expand their life. While cholelithiasis due to the high level of bilirubin has been extensively studied in thalassemia, reports concerning nephrolithiasis and thalassemia are fewer. Hemolysis, urogenital infections, diet or drugs rich in calcium and vitamin D, parathyroid gland diseases, hypercalciuria, hyperuricosuria, and hyperuricemia are equally accused as causes of nephrolithiasis in thalassemia. One hundred eighty-five patients with TM, following transfusion protocols (pre-transfused hemoglobin 9 mg/dl) were analyzed in our center. Ninety-two patients were under deferasirox (DFX 20 mg/kg/day). Nine of them experienced episodes of nephrolithiasis (Table 1). Two of them were splenectomized [1]. None had any illness predisposing to nephrolithiasis. The presence of the stone was confirmed by an ultrasound. The chemical analysis of the excreted stones confirmed a calcium oxalate calculi. Four changed their chelation therapy to deferiprone alone or in combination. None of them had similar episode in the last year of followup with the recommendations for increase water intake and lower calcium intake. Transfusion is a life-saving measure for TM patients, but it loads the body with iron that causes organ damages like endocrinopathies, cardiomyopathy, and hepatic failure. Survival of patients has improved due to the regular iron chelation. Nowadays, due to extension of life expectancy, beta thalassemic patients have additional pathological problems. Renal function may be affected in TM both by iron overload and by hyperuricemia due to increased breakdown of RBCs. Also, hypercalcemia and hypercalciuria and acid–base disbalance, especially in acid urine PH, are considered responsible for renal stones in TM [2]. Several authors have reported renal tubular dysfunction in TM patients such as proteinuria, hypercalciuria, and hyperphosphaturia [3–7]. Recently, a study showed that renal hyperfiltration was common in TM patients [8]. Regular transfusions improved the abnormally high creatinine clearance of the irregularly transfused patients. Hypercalciuria and albuminuria were also common. Hypercalciuria is more probably associated with systematic transfusions [9]. Recently, the orally administered chelation agent DFX is reported as nephrotoxic. Clinical trials have shown that DFX is effective in adults and children. Its recommended starting dose (20 mg/kg/day) can be modified dependently on the patient. Mild, nonprogressive increase in serum creatinine has been observed in approximately one third of patients. Creatinine levels returned largely to normal [10]. Nephrolithiasis is observed in TM patients receiving DFX or deferiprone as chelation therapy, but the causes are unknown. In our unit, 9 out of 92 patients treated with DFX were admitted with renal colic. In the same period of time, only 1 out of 93 patients treated with other chelators had similar experience. However, more studies are needed to verify the correlation of nephrolithiasis and DFX. Similarly, it is still unknown whether treatment with calcium and V. Efthimia :A. Agapidou :M. Economou : E. Vetsiou :A. Teli : V. Perifanis Thalassaemia Unit, Ippokratio Hospital, Konstantinoupoleos 49, Thessaloniki 54642, Greece

Five Years of Deferasirox Therapy for Cardiac Iron in β-Thalassemia Major

Abstract Myocardial siderosis in β-thalassemia major (β-TM) remains the leading cause of death. Deferasirox (DFX), a new iron chelation treatment, has proved to be effective in reducing or preventing cardiac iron burden in thalassemic patients according to clinical trials with maximum duration of up to 3 years except one that was recently published and lasted 5 years. The aim of this study was to evaluate the efficacy of DFX in reducing or preventing cardiac iron burden in 23 patients with β-TM after 5 years of therapy. All patients had a magnetic resonance imaging (MRI) T2* evaluation of their cardiac iron load before starting DFX therapy and after a period of 5 years. Ferritin levels and left ventricular ejection fraction (LVEF) were also evaluated at the same time. Deferasirox was administered in a starting dose of 30 mg/kg/day and never increased to more than 40 mg/kg/day. The MRI T2* cardiac iron load mean values before DFX was 32.82 ± 10.86 ms, and after 32.13 ± 7.74 ms, showing a stability in MRI T2* myocardial value but a significant improvement in two patients with an intermediate iron load (12 vs. 23 ms). The mean LVEF value was 68.43 ± 7.08% before treatment with DFX and 67.95 ± 5.94% after DFX therapy without significant change. Our results confirm previous studies that DFX is considered an effective chelating agent used as monotherapy for at least 5 years and is more efficacious in moderate to severe cardiac iron loaded thalassemic patients.

Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/β + -thalassemia patient: A rare and challenging condition

The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/β(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/β(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome.

Safety And Efficacy Of 4 Years Of Deferasirox Treatment For Sickle Cell Disease Patients

Deferasirox (DFRA) is a novel oral chelator agent for treatment of iron overload. Although well established in the treatment of β-thalassemia major (β-TM), it has not yet been fully investigated in patients with sickle cell disease. The aim of this report is to present the preliminary results of a pilot study assessing the effect of 4 years of DFRA treatment in six patients with sickle cell disease who are in need of recurrent transfusions. Our results show a significant reduction of ferritin levels and improvement of liver hemosiderosis, assessed by means of magnetic resonance imaging T2* (MRI T2*). None of the patients presented any serious adverse effects and the treatment was well tolerated. These results are in accordance with previous studies about the use of DFRA in sickle cell disease.

Rivaroxaban Use in Patients with Hemoglobinopathies

Abstract The use of rivaroxaban in patients with hemoglobinopathies and thrombotic events has not been studied extensively. Here we present eight cases of such patients, five receiving rivaroxaban for stroke and systemic embolism prevention due to non-valvular atrial fibrillation and three for deep vein thrombosis treatment. The follow-up period ranged from 6 to 34 months. During this period none of the patients experienced any thrombotic or bleeding event.There were no other adverse events reported. Further studies with larger numbers of patients with hemoglobinopathies are needed to determine the use of rivaroxaban and ensure its safety in this patient setting.

Evaluation of Mental Health and Physical Pain in Patients with β-Thalassemia Major in Northern Greece

Abstract β-Thalassemia major (β-TM) is a chronic, genetic blood disorder. Patients are considered to be vulnerable to emotional and behavioral problems. The aim of this study was to assess mental health and somatic pain of patients with homozygous β-TM, who are systematically transfused in our unit. In this survey, 54 adult patients were studied. The general health questionnaire (GHQ-28) was used as mental health assessment model aimed at detecting mental disorders. The model of Binary was used as scoring method of GHQ-28. Overall ratings below 5 indicate no psychiatric problem, while a total score over or equal to 5 indicated the likelihood of a psychiatric disorder. The visual analogue scale (VAS) of pain was used as model for pain evaluation. One out of four examined patients who presented with a GHQ-28 score above or equal to 5 had an increased chance of being diagnosed with a psychiatric disorder. Concerning the pain, the majority of the studied patients scored between 1 and 3, meaning that they were feeling mild pain. There was no statistical significant correlation between age and GHQ-28 score. There was a statistical significant correlation between age and somatic symptoms (p = 0.026), anxiety and somatic symptoms (0.004) as well as anxiety and depression (p = 0.022). Thalassemic patients tend to be diagnosed with psychiatric disorders and it seems that they do not feel severe pain. More quantitative and comprehensive studies have to be conducted in order to estimate specific effective factors in psychosocial health.

Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with Sickle Cell/ β (+) Thalassemia.

Sickle cell/β + thalassemia (Hb S/β +thal) is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β +thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β +thal.