International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

IL-17 and IL-23 levels in patients with early-stage chronic lymphocytic leukemia.

OBJECTIVE: Cytokines produced by bone marrow mesenchymal stem cells are important components of the tumor microenvironment in chronic lymphocytic leukemia (CLL). The roles of IL-17 and IL-23 in both autoimmune diseases and tumor growth have been demonstrated. The role of the IL-17/23 axis in apoptosis has also been demonstrated in studies. Autoimmune cytopenias are common in CLL. In this study, we aimed to compare IL-17/IL-23 levels in early-stage CLL patients with healthy controls. METHODS: After obtaining ethical approval from the local ethics committee, 22 patients with early-stage chronic lymphocytic leukemia and 21 healthy control groups were included in this study. IL-17 and IL-23 were analyzed using the enzyme-linked immunosorbent assay method. RESULTS: The findings showed that the median IL-23 level was lower in men in the chronic lymphocytic leukemia group than women. There was a positive correlation between IL-17 and IL-23 levels in both the control group and the chronic lymphocytic leukemia group. There was no significant correlation between stage and IL-17 and IL-23 levels in chronic lymphocytic leukemia patients. CONCLUSION: Results of studies conducted on IL-17 and/or IL-23 in chronic lymphocytic leukemia in the literature are not consistent. These inconsistent results can be explained by the fact that the immune system develops differently in each individual due to environmental factors, past infections, intestinal flora, vaccines, ethnicity, and even gender. Therefore, it can be hypothesized that the development and application of personalized immunotherapy strategies instead of standard therapy in chronic lymphocytic leukemia may increase therapeutic success rates.

Acquired Combined Factor Deficiency: Case Report.

BACKGROUND: Acquired hemophilia is a rare bleeding disorder. Difenacoum (superwarfarin), an antivitamin K anticoagulant, has been commonly used as a rodenticide. Factors II, VII, IX, and X are reduced as a result of this inhibition. METHODS: In this article, we have presented a case that had been exposed to superwarfarin according to our consideration, but for which factor XII, VIII, XI, V deficiency and presence of inhibitor could not be explained. RESULTS: Coagulation tests of the patient who applied for hematuria were prolonged. Factor II, V, VII, VIII, IX, X, XI, XII were low; antinuclear antibody, antiphospholipid antibody IgG, and anti-double stranded DNA antibodies were positive. When questioned, he admitted that they used rat poison in the bakery. In addition to fresh frozen plasma, vitamin K and plasma complex concentrate, factor VIII and factor IX were started. However, sufficient response could not be obtained since there were inhibitors against factor VIII and factor IX. Three sessions of plasmapheresis were performed to clear antibodies and immunosuppressive treatment was started. While coagulation tests were still long, there was no new bleeding and hematuria stopped. CONCLUSIONS: Immunosuppressive treatment and plasmapheresis may be tried if the replacement of deficient factors is not sufficient in acquired factor deficiency.

Can ELABELA be a novel target in the treatment of chronic lymphocytic leukaemia?

BACKGROUND: It has been shown that bcl2, bcl-XL and mcl-1 protein levels are high in chronic lymphocytic leukemia cells, and resultantly, apoptosis does not occur chronic lymphocytic leukemia cells. Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein coupled receptor called apelin receptor. Studies have shown that ELA inhibits apoptosis by inhibiting apoptotic proteins and activating anti-apoptotic proteins. Proteins and genes involved in apoptosis are valuable for targeted cancer therapy. We hypothesized that serum levels may be increased in patients with chronic lymphocytic leukemia based on the antiapoptotic effect of ELA. We compared serum ELABELA levels of healthy volunteers and patients with chronic lymphocytic leukemia. We aimed to draw attention to a new molecule worthy of research in targeted cancer treatment. METHODS: Forty two untreated CLL patients and 41 healthy volunteers were included in the study. Serum ELA levels were measured by using enzyme-linked immunosorbent assay kits (Dhanghai Sunred Biological Technology co. Ltd), automated ELISA reader (Thermo Scientific, FINLAND) and computer program (Scanlt for Multiscan F.C.2.5.1) in accordance with the manufacturer's instructions. Statistical analysis was done by Statistical Package for Social Sciences for Windows 20 (IBM SPSS Inc., Chicago, IL) ve MedCalc programs. ELA and variables related to CLL were correlated with Spearman correlation anlysis test. ROC analysis and Youden index method were used to determine a cut off point for ELA. All p-values were 2-sided with statistical significance at 0.05 alpha levels. RESULTS: In our study, we found that serum ELA levels were significantly higher in patients with CLL. CONCLUSIONS: This study highlights that ELA targeting may be a potential therapeutic option for treating CLL.

Detection of α-Thalassemia by Using Multiplex Ligation-Dependent Probe Amplification as an Additional Method for Rare Mutations in Southern Turkey.

α-thalassemia is the most common single gene disorder in the Cukurova Region in Turkey. It is therefore routinely screened, including premaritally, in our region. The heterogeneous molecular basis of the disease makes α-thalassemia mutation detection difficult and complex. Besides well established methods, multiplex ligation dependent probe amplification (MLPA) is known as an effective, simple and specific method for the detection and characterization of deletions and duplications. We employed MLPA testing to 30 patients with hematological parameters suggestive of α-thalassemia carrier status but was negative for α-thalassemia with conventional reverse dot blot hybridization (RDB). We found α-globin gene deletions in 3 out of 30 (10 %) patients with MLPA. We propose that MLPA can be used as a second tier test in addition to other techniques such as RDB to identify α-thalassemia carriers in high prevalence regions such as ours, thereby allowing clinicians to provide accurate genetic counselling.

Does corticosteroid treatment cause prolonged recovery and increased total bilirubin level in severe ADAMTS-13-deficient TTP patient?

A 41-year-old female patient complaining of fatigue, headache, mild confusion, and rush on her lower extremities was admitted to our emergency department. Laboratory tests revealed that he had anemia, thrombocytopenia, and increased levels of indirect bilirubin and lactic dehydrogenase (LDH) in blood tests. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). The best supportive care was provided. Therapeutic plasma exchange (TPE) and 1 mg/kg methylprednisolone treatments were administered. On the 10th day of treatment, LDH level and fragmented red blood cells in peripheral blood smear were decreased, but his direct and indirect bilirubin levels increased despite the fact that he was treated with 1 mg/kg methylprednisolone and TPE. The patient had severe ADAMTS-13 deficiency. After discontinued steroids treatment, his bilirubin level normalized within 4 days. On the 4th day after bilirubin level normalized, vincristine treatment was administered. TPE was also continued. There was no consensus about the optimal schedule for discontinuing plasmapheresis therapy, and also we observed total bilirubin level improvement with discontinued corticosteroid treatment. In this case, corticosteroid treatment was linked with the increase of total bilirubin level in severe ADAMTS-13-deficient TTP patient.

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: a retrospective multicenter study.

UNLABELLED: Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AIM: We aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. PATIENTS AND METHODS: One hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. RESULTS: Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. CONCLUSIONS: TPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.