Irfan Kuku

Platelet counts in adults with iron deficiency anemia

In adults with iron deficiency anemia (IDA), abnormal platelet counts were seen in several studies. However we retrospectively examined the clinical records of a larger number of adults with IDA to assess abnormal platelet counts. From November 2006 to April 2008, 615 consecutive adults (73 men and 542 women; age range, 16–88 years) with IDA were included in this study. The mean initial hemoglobin was 9.0 ± 1.8 g/dL (range 2.7–12.8 g/dL), and the mean initial platelet count was 304 × 103/µL ± 92.3 (range, 105–700 × 103/µL). The initial platelet counts were normal in 520 (84.6%) adults with IDA. Thrombocytosis (>400 × 103/µL) and thrombocytopenia (<150 × 103/µL) were detected in 82 (13.3%) and 13 (2.1%) adults with IDA, respectively. In conclusion, thrombocytosis was seen at lower rates in our study. Furthermore, this study shows that mild thrombocytopenia is not so rare in adults with IDA.

Preventive effect of melatonin on bleomycin-induced lung fibrosis in rats

Abstract:  Oxidative stress has an important role in the pathogenesis of idiopathic pulmonary fibrosis. Melatonin has direct and indirect free radical‐detoxifying activity. The present study investigated whether melatonin treatment attenuates bleomycin‐induced lung fibrosis in rats. A group of rats was given one dose of bleomycin while the control animals were given saline. The first dose of melatonin (4 mg/kg/day) was given 2 days before the bleomycin injection. At day 14, fibrotic changes were evaluated using Aschofts criteria and lung hydroxyproline content. Bleomycin produced a 2.7‐fold rise in the fibrosis score that was decreased 65% by melatonin (P < 0.05) and a 1.4‐fold increase in hydroxyproline content which was completely prevented by melatonin. Protein carbonyl and thiobarbituric acid reactive substances levels, which were significantly elevated in the bleomycin treated rats, were significantly attenuated by melatonin. Bleomycin administration significantly reduced the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) in lung tissue. The reduction in CAT activity was prevented by melatonin but SOD and GSH‐Px were not influenced. These results revealed that melatonin may prevent the development of bleomycin‐induced lung fibrosis via the repression of protein and lipid peroxidation.

Serum proinflammatory mediators at different periods of therapy in patients with multiple myeloma.

Multiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells within the bone marrow. Several cytokines have been demonstrated to be involved in the control of growth, progression, and dissemination of MM. We determined serum levels of interleukin-1β (IL-1β), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in 14 newly diagnosed MM patients. The median age of the patients was 63.4 ± 10.8 years and all of the patients were stage III (classified according to the Durie-Salmon classification). The same parameters were measured in 15 healthy controls. In addition, we also examined the effects of vincristine-adriamycin-dexamethasone (VAD) therapy on the same parameters and mediators as well as the relationship among the parameters in the same patient groups. The serum concentrations of TNF-α, IL-1β, sIL-2R, IL-6, IL-8, and CRP (18.6 ± 3.7 pg/mL, 10.1 ± 2.8 pg/mL, 730 ± 220 U/mL, 11.4 ± 3.3 pg/mL, 23.9 ± 8.3 pg/mL, and 49.9 ± 19.5 mg/dL, resp) were significantly higher in newly diagnosed MM patients than in healthy controls (P < .0001). All of the parameters were found to be significantly reduced after chemotherapy. In conclusion, we found that after the VAD therapy, the level of these cytokines which are thought to play an important role in the pathogenesis of MM was significantly suppressed. This is the first study demonstrating strong impact of VAD treatment on circulating mediators of sIL-2R and IL-8 levels parameters.

Oxidant/antioxidant Parameters and their Relationship with Chemotherapy in Hodgkin's Lymphoma

This study investigated changing levels of serum oxidant/antioxidant with chemotherapy and their relation to treatment in 34 Hodgkins lymphoma patients. The patient population consisted of 19 males and 15 females. Mean age was 30.41 ± 12.08 years. All patients received the adriamycin, bleomycin, vincristine and dexamethasone (ABVD) treatment protocol. Blood samples were taken before treatment, and on days 1 and 7 during treatment for measurement of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and enzyme activities. After ABVD treatment, mean free radical levels were increased and antioxidant levels were significantly decreased in the serum. ABVD treatment results in an increase of free radical levels and a decrease of antioxidant levels in the serum of patients with Hodgkins lymphoma.

Effects of Cyanocobalamin on Immunity in Patients with Pernicious Anemia

Objective: The aim of the study was to evaluate the role of vitamin B12 in patients with pernicious anemia. Materials and Methods: This study was conducted prospectively at the Turgut Özal Medical Center, Department of Hematology, between April and November 2002. Absolute numbers and ratio of the surface antigens of T and B lymphocyte subgroups, CD4/CD8 ratio were calculated in order to evaluate changes in leukocyte and lymphocyte numbers; natural killer (NK) cell count, serum C3, C4, and levels of immunoglobulins G, A, and M were also measured to evaluate vitamin B12 effect on immunity. Values obtained before treatment with cyanocobalamin were compared with those found during peak reticulocyte count. Results: In vitamin B12-deficient patients, absolute numbers of CD4+ and especially CD8+ lymphocytes were found to be decreased; CD4/CD8 ratio increased, and NK cell activity was depressed. After cyanocobalamin treatment, absolute numbers and percentage of lymphocyte subgroups were elevated. Increased CD4/CD8 ratio and depressed NK cell activity were restored and levels of C3, C4, and immunoglobulins were elevated. Conclusion: These findings suggest that vitamin B12 has important immunomodulatory effects on cellular immunity, and abnormalities in the immune system in pernicious anemia are restored by vitamin B12 replacement therapy.

Rheumatic diseases and chronic myelogenous leukemia, presentation of four cases and review of the literature

We report four patients with rheumatic disease (RD) and chronic myelogenous leukemia (CML). In two patients with Behcet’s disease (BD) and rheumatoid arthritis (RA), CML developed after RD, in two patients with diffuse cutaneous systemic sclerosis and spondyloarthropathy, RD was diagnosed after CML. A variety of interactions have been described between hematological malignancies and RD. Nevertheless, few cases of RD have been documented associated with CML. It is unclear whether the development of CML in patients with RD and RD development after CML occurs by chance alone, is due to the underlying disease, or is facilitated by drugs. Whatever the cause is, it should be kept in mind that CML may develop in the course of RD and RD may be seen in CML patients.

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.

A life-saving therapy in Class I HELLP syndrome: Therapeutic plasma exchange

HELLP syndrome, which can affect multiple organ systems and cause maternal and fetal mortality, is a serious complication of pregnancy characterized by microangiopathic hemolytic anemia, elevation of liver enzymes, and thrombocytopenia. Delivering the infant usually suffices for the treatment of this syndrome. In cases with Class I HELLP syndrome, however, the clinical picture may rapidly deteriorate despite delivery. In this paper we presented the outcomes with the use of therapeutic plasma exchange in cases with class I HELLP syndrome. This study included 21 patients diagnosed with the Class I HELLP syndrome at Inonu University Faculty of Medicine, Department of Hematology between 2011 and 2014. A central venous catheter was placed and plasma exchange therapy was begun in patients unresponsive to delivery, steroid, and supportive therapy (blood and blood products, antihypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. All patients underwent therapeutic plasma exchange for three sessions each with a 1:1 volume. Hemogram and biochemical parameters of the patients were evaluated before and after the procedure. According to results, there was a statistically significant decrease in total bilirubin, LDH, AST, and ALT levels whereas a significant increase in platelet count was observed. Hemoglobin levels were increased, although this increase was not statistically significant. HELLP syndrome is primarily treated with the delivery of infant; however, some cases may show disease progression despite completion of delivery. As a potential cause of both maternal and fetal mortality, HELLP syndrome condition should be aggressively treated. Therapeutic plasma exchange is one of the available treatment options. Our study has found that postpartum use of plasma exchange therapy within 24 hours is an efficient and lifesaving treatment choice in Class I HELLP syndrome.

Retrospective Analysis of Patients with Idiopathic Thrombocytopenic Purpura from Eastern Anatolia

Objective: We evaluated the clinical features and the effects of various treatment modalities on the clinical course in patients diagnosed with idiopathic thrombocytopenic purpura (ITP). Materials and Methods: Retrospective investigation of the medical records of 168 patients at our center between 1994 and 2005 was done. Results: Of the 168 patients, 115 (68.4%) were women and 53 (31.6%) men. At initial diagnosis, the median age of the patients was 33 years (range: 15–91) and 139 (82.7%) had signs of bleeding. Follow-up was complete in 130 patients and the median follow-up was 27 months (range: 3–132). Initial treatment with either standard or high-dose steroid as first-line therapy was begun in 123 (73.2%) of the 168 patients. Complete remission (CR) was achieved in 56% of the patients. Sixty-one (61) patients who were followed up regularly received second-line therapies. CR was achieved in 45.8% of the patients who received steroids as second-line therapy. Within a median follow-up of 7 months, 27.2% of these patients relapsed. Splenectomy was performed in 26 patients and CR was obtained in 72% of the 25 patients regularly followed up. CR obtained by splenectomy was significantly higher than that obtained by steroids (p < 0.001). The 10-year disease-free survivals in patients who used steroids and who underwent splenectomy were 15 and 61.6%, respectively. Conclusion: Steroid therapy is effective both in the initial and relapse periods. Splenectomy is the treatment of choice for those ITP patients refractory to steroid therapy and younger than 40 years of age.

Leukapheresis in acute myeloid leukemia patients with hyperleukocytosis: A single center experience

Hyperleukocytosis is defined as WBC count above 100,000/mm(3) in peripheral blood. Increased WBC count leads to leukocyte aggregation, increased blood viscosity, and consequently results in stasis in small blood vessels. Ultimate neurological, pulmonary, gastrointestinal complications, coagulopathy, and tumor lysis syndrome cause increase in morbidity and mortality. Leukapheresis is a treatment modality used for hyperleukocytosis. In patients presenting with hyperleukocytosis the indications for leukapheresis were accepted as having symptoms of leukostasis and prophylactic. Indications for leukapheresis in prophylactic group evaluated according to WBC count. We report a single center experience about leukapheresis in managing 31 AML patients with hyperleukocytosis. In addition to demographic characteristics, disease-related clinical and laboratory findings of the patients were recorded. Survival rates were also calculated. Ten patients were female. The most common of AML subtype was AML-M2. The median number of leukapheresis per patient was 2 and totally 60 leukapheresis cycles were performed in all patients. There was a significant decrease in WBC count and LDH level after leukapheresis as compared with the baseline values (p < 0.05). Early and total mortality were 16.1% and 58.0%, respectively. Alive and died patients were evaluated according to baseline WBC, LDH; increased WBC count and LDH level were found in died patients (p < 0.05). According to leukapheresis indications, patients were divided into two groups: 14 patients in symptomatic leukostasis, 17 patients in prophylaxis. No statistically significant differences were noted between both groups in leukapheresis effectiveness, mean survival time, early and total mortality rate (p > 0.05). None of our patients suffered serious side effects and tumor lysis syndrome during or after apheresis. Leukapheresis is an effective and safe approach to reduce WBC counts in patients with AML with hyperleukocytosis. Further evidence-based data obtained from larger sample sizes are required to better understand the impact of prophylaxis leukapheresis on early and total mortality of AML patients with hyperleukocytosis.