Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience.

OBJECTIVE: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. MATERIALS AND METHODS: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. RESULTS: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. CONCLUSION: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

Intensive menstrual bleeding successfully treated with recombinant factor VIIa in Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare inherited qualitative platelet disorder due to the deficiency or defect of platelet membrane glycoprotein (GP) IIb/IIIa complex. Symptoms include purpura, petechiae, bruising, gingival bleeding, epistaxis, and menorrhagia. Platelet transfusion is considered the standard therapy for securing hemostasis in patients with GT when local measures and antifibrinolytic agents are inadequate. However, repeated platelet transfusions may result in GP IIb/IIIa and/or human leukocyte antigen (HLA) immunization and development of platelet refractoriness. Recombinant factor VIIa (rFVIIa) has been introduced as therapeutic alternative and has been suggested to be effective. Recombinant factor VIIa is indicated in Europe for the treatment of GT refractory of platelet transfusion. In previous studies, rFVIIa has been used in the prophylactic treatment of bleeding in patients with GT undergoing pelvic surgery, cesarean section, and vaginal delivery. In this article, we present a case of intensive menstrual bleeding refractory to previous antifibrinolytic agents and platelet transfusions but which responded well to treatment with rFVIIa. To our knowledge, there is no study or reported case in the literature reporting successful use of rFVIIa in a patient with excessive menstrual bleeding due to GT.

Secondary involvement of the breast in T-cell non-Hodgkin lymphoma, an unusual example mimicking inflammatory breast carcinoma.

Non-Hodgkin lymphoma of the breast is a rare malignancy and present with almost equal frequency either as a primary or a secondary disease. Survival is poor in most cases of secondary breast lymphoma because of their advanced stage. We report a 35-year-old woman presenting with dyspnea as well as swelling, tenderness, and ruddiness in the left breast with non-cyclic pain for several months and maculopapular skin eruption in the same breast. Physical examination revealed fixed lymphadenopathies in both axillary regions. Radiologic evaluations (bilateral mammaograpy and ultrasonography) showed skin thickening in the left breast, asymmetrical densities in both breasts, and confirmed lymphadenopathies in the axillary regions. Excisional biopsies were performed to the left axillary lymph nodes and the breast skin eruptions. The histologic and immunohistochemical features were diagnosed as an ALK (-) anaplastic large cell lymphoma. A Computed Tomography examination was performed for staging the lymphoma and then chemotherapy was started. Thirty months after the diagnosis, the patient is still alive with disease. Because of the presence of systemic symptoms such as skin involvement and generalized lymphadenopathies (mediastinal, axillary or cervical), T cell lymphoma cases with breast involvement could mimic the clinical presentation of inflammatory breast carcinoma. Pathologic examination is needed for the correct diagnosis.

The frequency of factor V Leiden and concomitance of factor V Leiden with prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene mutation in healthy population of Denizli, Aegean region of Turkey.

Factor V Leiden causing activated protein C resistance is the most common inherited form of thrombophilia leading to thrombosis. Its frequency shows great ethnic and geographic variations. The aim of this study was to determine the frequency of FV Leiden and coinheritance of FV Leiden with two other frequent hereditary thrombophilia causes, namely, prothrombin G20210A and methylene-tetrahydrofolate reductase (MTHFR) C677T mutation in the Aegean region of Turkey. The study population consisted of 1030 (500 men and 530 women) apparently healthy subjects. Functional resistance to activated protein C (APC) was measured by using the test kit STA staclot APC-R ((Diagnostica Stago, Asnieres, France, Cat. No. 00721). In subjects with APC resistance, molecular analyses of FV Leiden and of prothrombin G20210A and MTHFR C677T mutation were performed by using FV-PTH-MTHFR StripA (Vienna Lab, Labordiagnostika GmbH, Austria) kit, which was based on hybridization of polymerase chain reaction (PCR) amplified DNA products with mutation-specific oligonucleotide probes. Functional APC resistance was present in 93 subjects (9%). FV Leiden mutation was found in 87 of 93 subjects with APC resistance by PCR method. The FV Leiden carrier frequency was found to be 8.4% (87/1030). Seventy-six individuals were heterozygous (7.3%), and 11 were homozygous (1.06%). Among the 87 subjects with FV Leiden mutation, 45 subjects had MTHFR C677T gene mutation (7 homozygous, 38 heterozygous) and 4 subjects had heterozygote prothrombin G20210A gene mutation. A combination of FV Leiden and prothrombin G20210A and MTHFR C677T gene mutation was detected in 3 subjects. The results indicate that FV Leiden prevalence is quite high and coexistence of FV Leiden with other hereditary causes of thrombosis such as prothrombin G20210A mutation and MTHFR enzyme defect is not rare in healthy population of Aegean region of Turkey.

Therapeutic plasma exchange for the treatment of thrombotic thrombocytopenic purpura: a retrospective multicenter study.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is fatal if it is not treated. Therapeutic plasma exchange (TPE) has resulted in excellent remission and survival rates in TTP patients. MATERIAL AND METHODS: We describe our experience with 52 TTP patients treated with TPE during the past eight years (65% of the patients were females; patient median age=34 years, range: 17-73). TPE was carried out 1-1.5 times plasma volume. Fresh frozen plasma (FFP) or cryosupernatant plasma (CSP) was used as the replacement fluid. TPE was performed daily until normalization of serum LDH and recovery of the platelet count to >150 x 10(9)/dL; TPE was then slowly tapered. Clinical, laboratory data, the number of TPE, other given therapy modalities, treatment outcomes and survival rate were evaluated retrospectively. RESULTS: Overall response (OR) and complete response (CR) rates were 77% and 60%, respectively. Response was excellent in 82.8% of the patients with primary TTP among whom 74.2% were CR. Additionally, there were statistical differences in terms of CR rate between patients with primary TTP and secondary TTP (74.2% vs. 29.4%; p=0.005). OR and CR rates were 79% and 57.9% in patients on TPE alone and 75.8% and 60.6% in patients on TPE+prednisolone, respectively (p=1 and p=0.8). Additionally, there were no statistical differences in terms of OR and CR rates between patients on TPE with FFP and CSP (p=0.25 and p=0.16, respectively). The presence of fever and the number of TPE were statistically important factors influencing the probability of response in multivariate logistic regression analysis (p<0.01 and p<0.01, respectively). Additionally, in multivariate Cox's regression analysis, the probability of survival was higher in patients who were responsive to treatment compared to patients who were unresponsive (p<0.001). CONCLUSION: TPE is an effective treatment for primary TTP; however, it may be used as adjunctive therapy for secondary TTP until it is under control. The addition of steroids to TPE had no advantage compared to TPE alone. CSP as replacement fluid is not superior compared to FFP. Fever appears to be a bad prognostic indicator. Therefore, prolonged treatment with TPE may be needed in patients with fever.

Heart rate variability in patients with rheumatoid arthritis.

Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance in the autonomic nervous system. Autonomic nervous system involvement in patients with rheumatoid arthritis (RA) has rarely been studied and has shown conflicting results. Our purpose was to determine if HRV showed changes in patients with RA in comparison with the normal population. Short-term analysis of HRV was performed for time-domain frequency in 42 patients with RA and 44 matched controls. In this analysis, patients displayed lower standard deviation of the mean than healthy subjects ( P<0.0001). Patients tended to display higher pNN50 and root-mean-square of successive difference values than did healthy subjects, but these differences were not statistically significant (P >0.05). In frequency domain analysis, the spectral measures of HRV showed reduced high-frequency (HF) values and an higher low-frequency (LF) values; as a result, the ratio between low and high frequencies (LF/HF), representative of sympathovagal modulation, was significantly increased (P=0.001, P=0.012, and P=0.003, respectively). Our data suggest an increase in sympathetic control of the heart rate in patients with RA. This increased sympathetic activity could play a key role in the development of ventricular tachyarrhythmias in RA and may be related to the higher incidence of sudden death in this disorder.