Marica Pavkovic, Aleksandar Petlichkovski, Aleksandar Stojanovic, Dejan Trajkov and Mirko Spiroski
Bgl II Polymorhism of the α2β1 Integrin Gene in Macedonian Population
Background. Glycoprotein (GP) Ia/IIa or α2β1 integrin is a platelet receptor for collagen and it mediates platelet adhesion to vascular subendothelium and is involved in thromb formation. Genetic polymorphism of α2β1 known as Bgl II affects the density of platelet GP Ia/IIa receptor on the platelet surface. Recent studies had shown relationship between this polymorphism and the risk of myocardial infarction, stroke, as well as diabetic retinopathy.
Aim. The aim of this study was to determine the frequency of this polymorphism in Macedonian healthy population.
Materials and Methods. We genotyped 217 healthy Macedonian individuals using the PCR and RFLP (restriction fragment length polymorphism) method.
Results. The allele frequencies in this study were 0.32 for Bgl II (+) allele and 0.67 for Bgl II (-). Distribution of Bgl II genotypes in Macedonian population was Bgl II (+/+) = 16/217 (7.3%), Bgl II (+/-) =107/217 (49.3%) and Bgl II (-/-) = 94/217 (43.3%).
Conclusion. Our results showed a slightly lower proportion of the Bgl II (+) allele (0.32) in Macedonian population, but not significantly different from other Caucasian population.
Marica Pavkovic, Slobodanka Trpkovska-Terzieva, Arif Latifi, Oliver Karanfilski, Lidija Cevreska and Aleksandar Stojanovic
Long-Term Follow-Up of Adult Patients with Idiopathic Thrombocytopenic Purpura after Splenectomy
Background: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by isolated thrombocytopenia and the absence of any underlying cause for thrombocytopenia. Corticosteroids are the standard first line treatment for patients with symptomatic disease, but in many cases, steroid tapering or withdrawal is followed by a decrease of platelet count and the need for additional treatment. Splenectomy is still the standard salvage therapy in cases refractory to corticosteroid therapy.
Aim: The aim of this study was to evaluate the long-term outcome of splenectomized patients with ITP.
Materials and Methods: We retrospectively analyzed medical records of 38 patients with ITP that underwent splenectomy after first-line steroid treatment. All patients were followed for at least one year.
Results: According to the results at the time of the last control, 28 patients had complete response (CR), but from those 28 patients only 22 (58%) were without therapy and 6 (22%) were receiving prednisone, azathioprine or both. These results indicate that only 22/38 (58%) of patients had long-lasting CR without therapy, 12 patients (31%) were receiving therapy and 4 patients (11%) had partial response without therapy.
Conclusion: In conclusion, splenectomy may be considered as safe and effective treatment for patients with ITP who failed to respond to firs-line treatment with corticosteroids.
Marica Pavkovic, Slobodanka Trpkovska-Terzieva, Tatjana Sotirova, Lidija Cevreska and Aleksandar Stojanovic
Immune thrombocytopenia (ITP) is an autoimmune disease of unknown etiology, characterized by isolated thrombocytopenia and the absence of any underlying cause for thrombocytopenia. Corticosteroids are the standard first line treatment for patients with symptomatic disease, inducing platelet count recovery in 70-80% of patients; but in many cases, steroid tapering or withdrawal is followed by a decrease of platelet count and the need for additional treatment. Splenectomy is still the standard salvage therapy in cases refractory to corticosteroid therapy. In the past decade monoclonal anti-CD20 antibodies (Rituximab) are being increasingly used in patients with refractory ITP and other autoimmune diseases. Recent studies show that Rituximab is useful in the treatment of patients with chronic and refractory ITP. We report two cases with chronic ITP treated with standard dose of Rituximab in four weekly doses and than continue to receive maintenance therapy with Rituximab for 2 years.
Marica Pavkovic, Rosica Angelkovic, Marija Popova-Simjanovska, Sonja Genadieva-Stavric, Lidija Cevreska and Aleksandar Stojanovic
Introduction of tyrosine kinase inhibitors (TKI) dramatically improves the treatment and survival of the patients with chronic myeloid leukemia (CML) in the last decade. Imatinib (IM) and other TKI induce larger percentage of complete cytogenetic response (CCyR) and major molecular response (MMR). Treatment resistance to TKIs still remains an important problem in the treatment of CML. The aim of our study was to analyze the molecular response (MR) in CML patients treated with Imatinib in our institution.
We have analyzed 53 CML patients (pts), 28 females and 25 males, treated with IM as a front or second line treatment. Only 15 pts were treated with IM as a front-line therapy, while 38 pts were pretreated with hydroxyurea or/and interferon. Median duration of CML was 6 years (range: 1 year- 17 years). Median duration of IM treatment was 3 years (range: 1 year-10 years). MR was analyzed in one up to 8 time points with Real Time Quantitative RT-PCR method.
Forty six pts (87%) had complete hematological response and 55% of pts had MMR, 13/53(24.5%) pts had MMR at 4.0-4.5 log and 16/53(30.2%) pts had MMR at 3.0-4.0 log. MMR was not achieved in 24/53(45.3%).
Our results have shown smaller percentage of patients (55%) with MMR, mostly due to the fact that larger proportion of patients (38/53) were heavily pretreated with HU or/and Interferon for a prolonged period of time, before the IM treatment. This is a major risk factor for acquisition of additional molecular and cytogenetic abnormalities responsible for IM resistance and poor treatment response.
Marica Pavkovic, Rosica Angelovic, Marija Popova-Simjanovska, Oliver Karanfilski, Slobodanka Trpkovska-Terzieva, Tatjana Sotirova, Lidija Cevreska and Aleksandar Stojanovic
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia due to platelet autoantibodies, causing an accelerated clearance of opsonized platelets by phagocytes. The etiology of ITP remains unclear, both genetic and environmental factors may have a role in the disease development. The aim of our study was to investigate a possible association of three single nucleotide polymorphisms (SNP) in the genes for interleukin beta (IL1B-511C/T), tumor necrosis factor beta (TNF+252G/A) and tumor necrosis factor alpha (TNFA-308G/A) with ITP. We have analyzed 125 adult patients with ITP and 120 healthy matched controls. Genotyping was performed by using PCR- RFLP methods.
Our results demonstrated significantly different genotype distributions and allele frequencies for TNFB+252G/A in patients with ITP, p = 0.005 and p = 0.009 with Yates correction. We did not find any significant differences in the genotype distribution or allele frequencies for the other two genes. We have found significantly different genotype distribution and allele frequencies for TNFA- 308G/A between patients with unresponsive and responsive ITP patients, p = 0.016 and p = 0.009. There were no significant differences in genotype distribution and allele frequencies for ILB-511C/T and TNFB+252G/A polymorphisms between those two groups of patients. We did not find any significant differences in genotype distribution and allele frequencies for all three polymorphisms between splenectomized and unsplenectomized ITP patients.
The obtained data indicate that the A allele of TNFB+252G/A is more frequent in these patients than in the controls and that this polymorphism may play a significant role in disease susceptibility. The A allele of TNFA-308G/A was more frequent in patients with unresponsive ITP, indicating that this gene polymorphisms may contribute to therapy resistance.
Marijan Bosevski, Irena Mitevska, Marica Pavkovic, Milka Klincheva, Emilija Trajkovska Lazarova, Emilija Velkova, Zlate Stojanoski, Nela Kostova, Savetka Paljoskovska Jordanova, Danica Petkoska, Mimi Mancheva, Aleksandra Gulevska, Marjan Baloski, Vasko Hadjiev, Gorjan Krstevski, Viktorija Kralevska, Ivica Bojovski, Mario Jovanovski, Vesna Nedelkovska and Atanas Gjorgievski
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.