Publications by authors named "Maria Podolak-Dawidziak"

20 Publications

  • Page 1 of 1

Platelet Reactivity and Response to Aspirin and Clopidogrel in Patients with Platelet Count Disorders.

Cardiol Res Pract 2021 17;2021:6637799. Epub 2021 Apr 17.

Department of Hematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Wrocław, Poland.

Background: Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce.

Aims: The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders.

Materials And Methods: This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018-2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5'-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs.

Results: The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7-28) vs. 23 (15-38) for AA AU and 32 (16-44) vs. 50 (32-71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79-118) for AA AU and 124 (89-139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34-60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120-180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; < 0.0002). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; < 0.001).

Conclusion: Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel.
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http://dx.doi.org/10.1155/2021/6637799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068533PMC
April 2021

Erythropoietin: a story of a discovery with Polish contribution.

Pol Arch Intern Med 2021 03 30;131(3):317-319. Epub 2021 Mar 30.

Department of Hematology, Jagiellonian University Medical College, Kraków, Poland.

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http://dx.doi.org/10.20452/pamw.15909DOI Listing
March 2021

World Thrombosis Day, October 10, 2020, and commemorating Professor Krystyna Zawilska.

Pol Arch Intern Med 2020 11 30;130(11):1021-1023. Epub 2020 Nov 30.

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http://dx.doi.org/10.20452/pamw.15694DOI Listing
November 2020

Platelet polyphosphate level is elevated in patients with chronic primary thrombocytopenia: A preliminary study.

Adv Clin Exp Med 2020 Sep;29(9):1051-1056

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Poland.

Background: Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation.

Objectives: To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation.

Material And Methods: The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels.

Results: The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation.

Conclusions: The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.
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http://dx.doi.org/10.17219/acem/125430DOI Listing
September 2020

Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study.

Lancet Haematol 2019 Jun 16;6(6):e295-e305. Epub 2019 Apr 16.

Hospital Universitario La Paz, Autónoma University, Madrid, Spain.

Background: Emicizumab, a subcutaneously administered, humanised, bispecific, monoclonal antibody, is approved to treat people with haemophilia A of all ages with and without coagulation factor VIII (FVIII) inhibitors. HAVEN 4 assessed emicizumab prophylaxis administered as one dose every 4 weeks in adults and adolescents with haemophilia A, regardless of FVIII inhibitor status.

Methods: In this phase 3, multicentre, open-label, two-stage study, patients aged 12 years and older with severe congenital haemophilia A (<1% of normal FVIII activity in blood) or haemophilia A with FVIII inhibitors, undergoing treatment with either FVIII concentrates or bypassing agents were recruited from three sites in Japan and Spain for a run-in cohort, and from 17 sites in Australia, Belgium, Japan, Poland, Spain, and the USA for a subsequent expansion cohort. Participants in the run-in and expansion cohorts were given emicizumab subcutaneously 6 mg/kg every 4 weeks for 24 weeks or more; for patients in the expansion cohort this regimen was preceded by four loading doses of 3 mg/kg once weekly. In the run-in cohort, we assessed pharmacokinetics after single and multiple (every 4 weeks) subcutaneous administration of 6 mg/kg emicizumab and safety. In the expansion cohort, the efficacy endpoint was efficacy of prophylactic emicizumab in maintaining adequate bleed prevention, assessed in all patients who received at least one dose of emicizumab and reported as annualised bleed rates for treated bleeds, all bleeds (treated and untreated), treated spontaneous bleeds, treated joint bleeds, and treated target joint bleeds. Safety was assessed in all participants given emicizumab. This study is registered with ClinicalTrials.gov, number NCT03020160, and is ongoing.

Findings: Between Jan 30, 2017, and Feb 27, 2017, seven patients were enrolled into the initial run-in cohort, which confirmed the expected pharmacokinetic profile and safety of the regimen based on model-based simulations, providing sufficient evidence for opening of the expansion cohort (n=41), which was recruited and enrolled between May 24, 2017, and June 30, 2017. The annualised rate of treated bleeds was 2·4 (95% CI 1·4-4·3). 23 (56·1%; 95% CI 39·7-71·5) of 41 reported no treated bleeds and 37 (90%; 76·9-97·3) reported zero to three treated bleeds. The annualised bleed rate was 4·5 (95% CI 3·1-6·6) for all bleeds, 0·6 (0·3-1·5), for treated spontaneous bleeds, 1·7 (0·8-3·7) for treated joint bleeds, and 1·0 (0·3-3·3) for treated target joint bleeds. The most frequent treatment-related adverse event was injection-site reaction (nine [22%] of 41 patients). We observed no thrombotic events or development of de-novo antidrug antibodies with neutralising potential or FVIII inhibitors.

Interpretation: Emicizumab given once every 4 weeks showed clinically meaningful bleed control while being well tolerated. This regimen could improve patient care by decreasing treatment burden and increasing adherence to effective prophylaxis, potentially decreasing the development of secondary complications for people with haemophilia A.

Funding: F Hoffmann-La Roche and Chugai Pharmaceutical.
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http://dx.doi.org/10.1016/S2352-3026(19)30054-7DOI Listing
June 2019

Recommendations for the diagnosis and treatment of patients with polycythaemia vera.

Eur J Haematol 2018 Jul 30. Epub 2018 Jul 30.

Division of Hematology and Blood Coagulation, Department of Internal Medicine I, Medical University of Vienna Hospital, Vienna, Austria.

Objectives: To present the Central European Myeloproliferative Neoplasm Organisation (CEMPO) treatment recommendations for polycythaemia vera (PV).

Methods: During meetings held from 2015 through 2017, CEMPO discussed PV and its treatment and recent data.

Results: PV is associated with increased risks of thrombosis/thrombo-haemorrhagic complications, fibrotic progression and leukaemic transformation. Presence of Janus kinase (JAK)-2 gene mutations is a diagnostic marker and standard diagnostic criterion. World Health Organization 2016 diagnostic criteria for PV, focusing on haemoglobin levels and bone marrow morphology, are mandatory. PV therapy aims at managing long-term risks of vascular complications and progression towards transformation to acute myeloid leukaemia and myelodysplastic syndrome. Risk stratification for thrombotic complications guides therapeutic decisions. Low-risk patients are treated first line with low-dose aspirin and phlebotomy. Cytoreduction is considered for low-risk (phlebotomy intolerance, severe/progressive symptoms, cardiovascular risk factors) and high-risk patients. Hydroxyurea is suspected of leukaemogenic potential. IFN-α has demonstrated efficacy in many clinical trials; its pegylated form is best tolerated, enabling less frequent administration than standard interferon. Ropeginterferon alfa-2b has been shown to be more efficacious than hydroxyurea. JAK1/JAK2 inhibitor ruxolitinib is approved for hydroxyurea resistant/intolerant patients.

Conclusions: Greater understanding of PV is serving as a platform for new therapy development and treatment response predictors.
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http://dx.doi.org/10.1111/ejh.13156DOI Listing
July 2018

MRP1 protein expression in leukemic stem cells as a negative prognostic marker in acute myeloid leukemia patients.

Eur J Haematol 2017 Nov 29;99(5):415-422. Epub 2017 Sep 29.

Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.

Background: It is well established that expression of multi-drug resistance (MDR) proteins (MDR1, BCRP, MDR3, MRP1, and LRP) in leukemic blasts correlates with acute myeloid leukemia (AML) patients' clinical response. Assuming that leukemic stem cells (LSC) are resistant to chemotherapy and responsible for relapse, it might be clinically relevant to evaluate the expression level of MDR proteins in LSC and relate it to the clinical outcome.

Methods: Bone marrow samples from 26 patients with de novo AML were labeled with antibodies to distinguish CD34+CD38-CD123+ LSC population and with antibodies against MDR1, BCRP, MDR3, MRP1, or LRP proteins. Multicolor flow cytometry was applied to evaluate the expression of MDR proteins in blasts and LSC.

Results: Nine of 26 patients with AML attained CR (30%). High negative correlation was found between MDR1 and LRP expression in blasts and the patient's remission. MDR proteins were expressed more frequently in LSC than in leukemic blasts. High negative correlation was also observed between remission achievement and MRP1 expression in LSC.

Conclusions: Our data present for the very first time the high negative correlation between MRP1 protein expression in LSC and AML patients' remission. It does strongly suggest that MRP1 expression in LSC is an adverse prognostic marker in patients with de novo AML.
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http://dx.doi.org/10.1111/ejh.12938DOI Listing
November 2017

Pregnancy exacerbates complications of acquired hemophilia in a patient with systemic lupus erythematosus.

Postepy Dermatol Alergol 2015 Jun 15;32(3):235-8. Epub 2015 Jun 15.

Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland. Head of the Department: Prof. Piotr Wiland MD, PhD.

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http://dx.doi.org/10.5114/pdia.2014.40964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495105PMC
June 2015

Induction therapy alters plasma fibrin clot properties in multiple myeloma patients: association with thromboembolic complications.

Blood Coagul Fibrinolysis 2015 Sep;26(6):621-7

aInstitute of Cardiology, Jagiellonian University Medical College, and John Paul II Hospital, Krakow bDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Wroclaw cDepartment of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice d1st Department of Hematology, City Hospital, Opole eDepartment of Hematology, Medical University of Lublin, Lublin, Poland.

Induction therapy in patients with multiple myeloma increases the risk of thromboembolism. We have recently shown that multiple myeloma patients tend to form denser fibrin clots displaying poor lysability. We investigated the effect of induction therapy on fibrin clot properties in multiple myeloma patients. Ex-vivo plasma fibrin clot permeability, turbidity, susceptibility to lysis, thrombin generation, factor VIII and fibrinolytic proteins were compared in 48 multiple myeloma patients prior to and following 3 months of induction therapy, mainly with cyclophosphamide-thalidomide-dexamethasone regimen. Patients on thromboprophylaxis with aspirin or heparins were eligible. A 3-month induction therapy resulted in improved clot properties, that is higher clot permeability, compaction, shorter lag phase and higher final turbidity, along with shorter clot lysis time and higher rate of D-dimer release from fibrin clots than the baseline values. The therapy also resulted in lower thrombin generation, antiplasmin and thrombin-activatable fibrinolysis inhibitor (TAFI), but elevated factor VIII. Progressive disease was associated with lower posttreatment clot permeability and lysability. Despite thromboprophylaxis, two patients developed ischemic stroke and 10 had venous thromboembolism. They were characterized by pretreatment lower clot permeability, prolonged clot lysis time, longer lag phase, higher peak thrombin generation, TAFI and plasminogen activator inhibitor -1. Formation of denser plasma fibrin clots with reduced lysability and increased thrombin generation at baseline could predispose to thrombotic complications during induction treatment in multiple myeloma patients. We observed improved fibrin clot properties and thrombin generation in multiple myeloma patients except those with progressive disease.
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http://dx.doi.org/10.1097/MBC.0000000000000315DOI Listing
September 2015

Porphobilinogen deaminase gene mutations in Polish patients with non-erythroid acute intermittent porphyria.

Adv Clin Exp Med 2015 Jan-Feb;24(1):63-8

Department of Hemostasis and Metabolic Disorders, Institute of Haematology and Transfusion Medicine, Warszawa, Poland.

Background: Acute intermittent porphyria (AIP) is an metabolic disorder characterized by a partial deficiency of the porphobilinogen deaminase, the enzyme of heme biosynthesis. The metabolic defect in AIP involves an approximately half-normal activity of porphobilinogen deaminase (PBGD, EC 4.3.1.8), the enzyme catalyzing condensation of four porphobilinogen molecules to hydroxymethylbilane. Due to tissue-specific alternative transcript splicing, the PBGD gene mutations within the range of exons 3-15 may lead to classical AIP involving erythrocytes and all the other tissues. Mutations within intron and exon 1 may result in the so-called non-erythroid AIP in which the PBGD activity is normal in erythrocytes and diminished in other tissues.

Objectives: The aim of the present study was to characterise molecular errors in the PBGD gene in Polish patients with non-erythroid AIP and to evaluate the efficacy of the DNA sequencing method in the early diagnosis of this disorder.

Material And Methods: Twenty five members of nine non-erythroid AIP families were assessed. In each of them DNA sequencing was performed using the Big Dye Terminator Cycle Sequencing Kit v.1.1 on the Hitachi 3730 Analyzer (Applied Biosystem, USA).

Results: Four mutations were detected in intron 1 of the PBGD gene, including one unreported novel mutation, 33+(4-12) del AGTGCTGAG, of an unknown biological mechanism, and three previously described mutations, i.e. 33+1 G > A, 33+2 T > C, 33+5 G > C, responsible for abnormal transcript splicing in the area of exon 1. Of 14 asymptomatic members of proband families in 6 subjects were diagnosed with AIP, and in 8 the AIP was excluded based on the DNA sequencing method.

Conclusions: DNA sequencing based analysis is the only reliable method for correct diagnosis of asymptomatic non-erythroid AIP patients with normal urinary excretion of heme precursors. The mutations found in Polish patients with non-erythroid AIP represented those of splice defect and resulted in abnormal exon 1 splicing.
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http://dx.doi.org/10.17219/acem/34555DOI Listing
June 2015

Altered plasma fibrin clot properties and fibrinolysis in patients with multiple myeloma.

Eur J Clin Invest 2014 Jun;44(6):557-66

Institute of Cardiology, Jagiellonian University Medical College, and John Paul II Hospital, Krakow, Poland.

Background: Multiple myeloma (MM) is associated with increased risk of venous and arterial thromboembolism. Formation of denser and poorly lysable fibrin clots is observed in patients with arterial and venous thromboembolism. We investigated fibrin clot properties and their determinants in MM patients.

Materials And Methods: Ex vivo plasma fibrin clot permeability, turbidity and susceptibility to lysis were evaluated in 106 MM patients at the time of diagnosis vs. 100 age- and sex-matched controls. MM patients had lower clot permeability (Ks ), compaction, indicating denser fibrin clots, impaired fibrin polymerization with longer lag phase and lower final turbidity (D-Dmax ), combined with hypofibrinolysis reflected by longer lysis time and slower rate of D-dimer release from fibrin clots (D-Drate ) compared with controls (all P < 0·001).

Results: Patients with IgG MM had lower Ks compared with IgA MM [5·9 (5·1-6·4) vs. 6·3 (5·9-7·2) 10(-9)  cm(2) ; P = 0·007] and longer lysis time compared with light-chain-disease patients [11·4 (10·9-12·3) vs. 10·7 (9·8-11·9) min; P = 0·022]. Of the fibrin variables, only Ks was significantly lower in patients with International Staging System (ISS) grade III than in those with ISS grade I and II [5·9 (4·9-6·6) vs. 6·2 (5·7-6·8) 10(-9)  cm(2) ; P = 0·015]. Multivariate analysis adjusted for age and fibrinogen showed that in MM patients elevated peak thrombin levels determine Ks and D-Dmax , while thrombin-activatable fibrinolysis inhibitor (TAFI) activity predicts Ks , t50% , D-Drate and lag phase.

Conclusions: Our study demonstrates prothrombotic fibrin clot phenotype in patients with MM, with a significant impact of increased thrombin formation and TAFI activity.
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http://dx.doi.org/10.1111/eci.12269DOI Listing
June 2014

Therapeutic problems in elderly patients with hemophilia.

Pol Arch Med Wewn 2012 ;122(11):567-76

Department of Hematology and Internal Diseases, Struś Hospital, Poznań, Poland.

Since the introduction of clotting factor concentrates, the life expectancy of patients with hemophilia has increased from 40 years in the 1960s to 60 or even 70 years today. In Poland, almost all elderly patients with hemophilia have arthropathy, the majority are infected with hepatitis C virus (HCV), and some even with hepatitis B or human immunodeficiency virus. Liver cirrhosis associated with HCV infection develops within 15 to 20 years in 20% to 30% of these patients. Coexistent diseases related to aging and affecting the heart, kidneys, and other organs constitute another challenge. To prevent ischemic heart disease, cardiovascular risk factors should be carefully monitored. The present paper describes the current recommendations for the use of antithrombotic therapy for acute coronary syndromes and atrial fibrillation in patients with hemophilia. Changes in the urinary system in hemophiliacs develop with age, often leading to dialysis. There is an urgent need for intensive physiotherapy and improved access to orthopedic treatment for patients with arthropathy. High‑risk surgical procedures in these patients should be performed in specialized centers with an experienced team and a coagulation laboratory. Older patients with mild hemophilia are at an increased risk for inhibitor development following intensive factor replacement therapy for surgical or invasive procedures. Pain control is a particular challenge due to contraindications to the use of many effective analgesics; another concern is the quality of life of these patients. An increasing number of older patients with hemophilia requires a comprehensive diagnostic and therapeutic approach, preferably at hematological centers.
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November 2013

Endothelial progenitor cells and left ventricle function in patients with acute myocardial infarction: potential therapeutic considertions.

Am J Ther 2012 Jan;19(1):44-50

Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.

Endothelial progenitor cells (EPCs) play a key role in angiogenesis and vascular repair, although their exact functions are still disputable. The impact of EPC on left ventricular ejection fraction (LVEF) during acute myocardial infarction (MI) in patients treated with primary percutaneous coronary intervention (PCI) is also under investigation. The aim of this study was to assess the impact of different populations of EPC on LVEF during and 6 months after acute MI treated with primary PCI. The study included 34 patients with documented acute anterior wall MI. The control group consisted of 19 apparently healthy subjects. Blood for EPC assessments was obtained during the first 24 hours after MI and at 7 days and 6 months after PCI. CD34⁺/CD133⁺/CD45⁻, CD34⁺/CD31⁺/CD45⁻, CD34⁺/CD105⁺/CD45⁻, and CD31⁺/CD133⁺/CD45⁻ cell types were studied by flow cytometry. Echocardiography has been performed simultaneously with the EPC measurements. We observed a significant elevation of CD34⁺/CD133⁺/CD45⁻, CD34⁺/CD105⁺/CD45⁻, and CD31⁺/CD133⁺/CD45⁻ EPC at 7 days after PCI in comparison with 24 hours and 6 months after the MI. Patients with preserved LVEF at 7 days after PCI had also higher levels of CD31⁺/CD133⁺/CD45⁻. Acute anterior wall MI treated with primary PCI is followed by enhanced mobilization of EPC among which a high level of CD31⁺/CD133⁺/CD45⁻ subtype was strongly associated with the most preserved LVEF for up to 6 months after the index event. These data may provide some insight for future therapeutic strategies.
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http://dx.doi.org/10.1097/MJT.0b013e3181e0cab3DOI Listing
January 2012

Pregnancy in a woman with polycystic ovary syndrome and myelodysplastic syndrome (in the form of refractory anemia) treated with allogeneic hemopoietic stem-cell transplantation (alloHSCT).

Gynecol Endocrinol 2010 Feb;26(2):135-8

Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wrocaw Medical University, Wrocaw, Poland.

The case of a 21-year-old patient is presented who was diagnosed simultaneously with myelodysplastic syndrome (MDS) in the form of refractory anemia and hormonal disturbances consistent with polycystic ovary syndrome (PCOS). The patient became pregnant 28 months after megachemotherapy and alloHSCT and delivered a healthy son. The patient's fertility was jeopardized due to both hormonal disturbances and megachemotherapy with cyclophosphamide and allogeneic transplantation; however, her age and body mass reduction in the peritransplant period were beneficial factors. Despite an autologous reconstitution after megachemotherapy and alloHSCT, the malignant neoplastic clone was eliminated and 5 years after transplant the patient remains free from the symptoms of MDS. Two years after the delivery her hormonal findings, including testosterone level, are within the norm, but menstrual bleeding remains irregular and there was a relapse of obesity. To the authors' knowledge, this is the first known case of pregnancy in a patient suffering from MDS and PCOS after HSCT from a sibling donor.
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http://dx.doi.org/10.3109/09513590903215474DOI Listing
February 2010

Therapeutic properties and safety of recombinant factor VIII and factor IX.

Pol Arch Med Wewn 2009 Jun;119(6):403-9

Department of Hematology, Jagiellonian University School of Medicine, Kraków, Poland.

Advances in hemophilia management in the 20th century enabled effective and early treatment of joint and other bleeds typical of this disease, also in a home setting. Prophylaxis became available as the optimal approach to prevent hemophilic arthropathy and improve patients' quality of life. To increase treatment safety, lyophilized plasma-derived factor VIII and IX concentrates were subjected to numerous procedures designed to decrease the risk of transmission of known and unknown pathogens. During the following years, recombinant factor VIII and factor IX preparations were developed to completely eliminate the risk. Recombinant factor concentrates were extensively studied in terms of their therapeutic properties, safety, and immunogenicity. This article reviews the current knowledge on efficacy and safety of recombinant factors VIII and IX.
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June 2009

[Anagrelide in the treatment of thrombocythemia essential (ET)].

Pol Arch Med Wewn 2004 Dec;112(6):1445-50

Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku AM we Wrocławiu.

Essential thrombocythaemia (ET), the most often occurring myeloproliferative disorder is a clonal malignant disorder arising from stem cell. The course of the disease is complicated by some severe thrombotic events and far less commonly by haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g. aspirin) and lowering platelet count (hydroxyurea or interferon alpha). Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation. The aim of the study was to evaluate the efficacy and side effects of anagrelide in patients with ET refractory to prior treatment with hydroxyurea. Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan. 1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males, (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5 mg) reduced platelet count in all patients. Median time of response was 3-4 weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons (55%) and partial remission 17 persons, and only one patient had platelet count slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms of low extremities deep venous thrombosis and in one transient ischaemic cerebral stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8 g/dL), and neither leukopenia nor disturbances of hepatic or renal function were observed. During the first two months of treatment with anagrelide some mild and transient side effects were noticed, eg. headache in 10 (25%), fluid retention in 8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of them continued therapy. Achieved platelet count reduction allowed in 2 ET patients safe performance of planned surgery (cholecystectomy, partial thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an effective drug for of ET patients refractory to hydroxyurea.
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December 2004

The expression of proliferating cell nuclear antigen (PCNA) and of nucleolar organizer regions (AgNORs) correlates with the morphological type of bone marrow plasma cells in multiple myeloma (MM).

Pol Arch Med Wewn 2003 Mar;109(3):257-63

Dept. of Haematology, Medical University of Wrocław.

Unlabelled: Proliferating cell nuclear antigen (PCNA) is a DNA polymerase delta accessory protein, and is an indicator of the proliferative state of the cell. Nucleolar organizer regions (NORs) are loops of DNA that carry the ribosomal RNA (rRNA) genes and are markers of aggressiveness for certain tumors.

Patients And Methods: This study tested the correlation between plasma cell morphology and PCNA and NOR expression in 50 multiple myeloma (MM) patients prior to therapy. 50 MM bone marrow trephine biopsies were studied using the monoclonal antibody PC-10 and the colloid silver nitrate method for identification of PCNA and AgNors, respectively.

Results: PCNA positive cells ranged from 2% to 100%, higher PCNA expression was observed in patients with immature type of MM (mean 29.5%, SD = 5.5), the highest expression was seen in plasmablastic type MM (mean 60.5%, SD = 22.6). The AgNOR count was also higher in MM with plasmablasts in the bone marrow (p < 0.001). In addition, the localization of AgNOR changed according to the type of MM: in 84% of mature and intermediate MM NORs were present in the central nucleus whereas in immature and plasmablastic MM NORs were dispersed or near the membrane. Elevated PCNA expression and AgNOR counts was also seen in MM patients with hyperviscosity coma as well as in patients with renal failure.

Conclusion: PCNA expression and AgNOR count in myeloma indicates the myeloma's proliferative activity and correlates positively with the cytomorphology of plasma cells and clinical outcome.
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March 2003

[Monoclonal antibodies in hematologic oncology].

Pol Arch Med Wewn 2002 May;107(5):469-73

Klinika Hematologii i Chorób Rozrostowych Krwi AM we Wrocławiu.

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May 2002

[Role of white cells and neoplastic cells in haemostasis].

Pol Arch Med Wewn 2002 May;107(5):431-6

Katedra i Klinika Hematologii i Chorób Rozrostowych AM we Wrocławiu.

The aim of this review was to assess the role of white cells and neoplastic cells in haemostasis.
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May 2002
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