Registry of inherited bleeding disorders in Poland--current status and potential role of the HemoRec database.

We present data collected in HemoRec, an Internet-based platform implemented in 2006 in 15 haemophilia treatment centres in Poland and compare them with the national registry of inherited bleeding disorders established since 1991 at the Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the current status of haemophilia treatment in Poland as well as future perspectives. Data on 1102 patients registered in HemoRec were analysed and compared with 4294 patients in the national registry (status as at 17.08.2009). The number of patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in the national registry. The mean age of all haemophilic patients registered in HemoRec is 26.2 years, compared with 37.3 years in the general Polish male population in 2008. The number of haemophilic patients with inhibitor registered in HemoRec is 102 compared with 155 in the national registry (resulting in a prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe haemophilia B patients). HemoRec includes data on a representative group of Polish haemophilic patients, mostly with haemophilia and haemophilia with inhibitor. von Willebrand's disease is largely under-registered in Poland. The survival of Polish haemophilic patients is shorter than that in the general population. The number of inhibitor patients in Poland is relatively large and should be decreased by wider availability of immunotolerance induction in 2010.

Assessment of oxidative/nitrative modifications of plasma proteins, selected ROTEM parameters and kinetics of fibrinogen polymerization in patients with multiple myeloma at diagnosis.

Patients with multiple myeloma (MM) are at increased risk of thrombosis. Growing evidence indicates that oxidative and nitrative modifications of proteins, including fibrinogen, may lead to changes in hemostasis. The study compares samples from patients with MM at diagnosis and healthy volunteers with regard to the oxidative/nitrative modifications of proteins, ROTEM and thrombin-catalyzed fibrin polymerization. The content of carbonyl groups in plasma proteins of patients with MM was significantly higher than in controls (2.981 vs. 1.807 nmol/mg of protein, p = 0.005), while no differences were seen in the concentrations of nitrated proteins. Maximum clot firmness readings were significantly higher in the samples of patients than in controls according to FIBTEM test (23.5 vs. 15 mm, p = 0.006). The lag time of the fibrin polymerization process and the velocity of clot lysis (V Lys) were found to be significantly higher in the group of MM patients than controls. In contrast, no marked differences were identified between studied groups in reference to maximal velocity of fibrin polymerization process (V max), maximal absorbance (A max) and plasmin amidolytic activity values. In conclusion, our study demonstrates that at the time of diagnosis, patients with MM demonstrated greater oxidative stress than healthy volunteers, which is reflected in a higher amount of carbonylated proteins. Some prothrombotic features found in ROTEM tests in MM patients were not confirmed by turbidimetry.

Activation of blood coagulation and the activity of cancer procoagulant (EC 3.4.22.26) in breast cancer patients.

The activity of cancer procoagulant (CP), prothrombin time (PT), activated partial thromboplastin time (APTT), the concentration of thrombin-antithrombin complexes (TAT) and the concentration of fibrinogen were analysed in blood of breast cancer patients scheduled for surgery. The serum level of CP activity was dependent on the stage of the disease. The CP activity was increased in 72% of patients with an early stage of cancer and in only 20% of patients with an advanced stage of the disease when compared to the baseline level for non-cancer controls. In all patients PT remained at normal levels (80-120%). There was no significant change in APTT (27-39 s) in early stage cancer patients. Only one patient with advanced cancer had APTT shortened to 23 s. Also one advanced stage patient had significantly elevated level of TAT (14.96 microg/l); in all other patients the concentration of TAT remained at normal levels (1-4.1 microg/l). Forty-four percent of early stage cancer patients and 22% of advanced cancer patients had an elevated level of fibrinogen (Fg) ( > 350 mg%). However, there was no correlation between the level of Fg and the CP activity (P > 0.05). The data suggest that: (1) serum CP activity increases at the early stage of breast cancer and decreases down to the normal level in the advanced stage of the disease; (2) there is no evidence of blood clotting activation in the early stage breast cancer patients; and (3) CP does not facilitate the activation of coagulation in the breast cancer patients or the level of such activation is below the sensitivity of assays used in the experiment.

Assessment of coagulation disorders in patients with acute leukemia before and after cytostatic treatment.

Coagulation disorders are often the reason for fatal bleeding in acute promyelocytic leukemia. Their occurrence as well as pathogenesis and prognostic significance in other subtypes of acute myelogenous leukemia and acute lymphoblastic leukemia is less known. Tests were carried out in 70 patients including 49 with AML and 21 with ALL. In all patients thrombin-antithrombin complexes (TAT), D-dimer (DD) and plasmin-antiplasmin complexes (PAP), antithrombin III activity, fibrinogen/fibrin degradation products, APTT and PT were determined. The tests were performed on diagnosis and after cytostatic treatment. The level of TAT, DD and PAP was elevated in 83% of the patients on diagnosis and in 90% after treatment. The highest values were observed in AML M3 patients. Among leukemic patients with normal levels of TAT, DD and PAP at diagnosis, cytostatic treatment had a negligible effect on the level of these markers. During remission the levels of these markers returned to the normal values while in patients without remission they were either elevated or returned to normal values. No correlation between the levels of activation markers and remission rate was reported. DIC was diagnosed in 13 patients including three after chemotherapy. The DIC was acute or subacute in AML and chronic in ALL patients. In the majority of acute leukemia patients there were already changes on diagnosis indicating coagulation activation. Except for AML M3, these usually had a subclinical course. The TAT, DD and PAP tests are not reliable markers of remission in acute leukemias.

Association of interferon gamma, tumor necrosis factor alpha and interleukin 6 serum levels with systemic lupus erythematosus activity.

We investigated serum level of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) using an enzyme-linked immunosorbent assay (ELISA) in 59 patients with systemic lupus erythematosus (SLE) and 16 healthy controls. We examined a possible association between serum levels of these cytokines and SLE activity, as well as correlation between IFN-gamma concentration and the level of TNF-alpha and IL-6 and also IL-6 and TNF-alpha. TNF-alpha and IL-6 were detectable in all 59 patients and normal individuals and their level was significantly higher in SLE patients than in the control group (p < 0.001 and p < 0.02, respectively). In contrast IFN-gamma was detectable in 23 (39%) patients and in only 3 (20%) healthy individuals. We found positive correlation between serum concentration of TNF-alpha and IL-6 with SLE activity and no such correlation with IFN-gamma. We also observed positive correlation between serum levels of IFN-gamma and TNF-alpha, IFN-gamma and IL-6 as well as TNF-alpha and IL-6. In conclusion, an increase in the serum levels of TNF-alpha and IL-6 may be useful markers for SLE activity.

Assessment of coagulation disorders and cancer procoagulant activity in patients with myelodysplastic syndromes.

Hemostatic disorders mainly due to thrombocytopenia represent an important clinical problem in patients with myelodysplastic syndromes (MDS). Much less is known about the possible coagulation abnormalities. Thirty patients with MDS were studied. Activity of cancer procoagulant (CP), concentrations of activation markers of coagulation and fibrinolysis such as thrombin-antithrombin complexes (TAT), prothrombin fragment 1+2 (F1+2) and D-dimers (DD) as well as standard coagulation tests were determined. Coagulation abnormalities concerned mainly patients with RAEB and RAEB-t. In this group the mean values of TATand F1+2 concentrations were significantly higher than in control indicating chronic coagulation activation similar to that observed in acute leukemias. CP activity in MDS patients did not differ from the control group.

Efficacy and toxicity of low-dose melphalan in myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia.

Effective therapy of myelodysplatic syndromes and acute myeloid leukemia originating from myelodysplastic syndrome has remained an unresolved problem. Advanced age of the patients and persistent pancytopenia make the treatment difficult. Despite large number of therapeutic options none of them is satisfactory. Recently palliative treatment with low-dose melphalan has been reported to have certain activity. The aim of the study was to evaluate the efficacy of low-dose melphalan in high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia with multilineage dysplasia (AML). Twenty three patients were eligible for the study: 8 with MDS and 15 with AML with multilineage dysplasia. All of them received oral melphalan in a daily dose of 2 mg. Median total dose of the drug was 120 mg (40-840 mg). Ten patients responded to the therapy. We observed complete remission (CR) in 4, partial remission (PR) in 3 and stabilization of the disease in 3 patients. Thirteen patients did not respond to the therapy. The survival time of the patients from the day of diagnosis and from the beginning of the treatment with melphalan was longer in patients responding to the therapy (median 15 and 10 months, respectively) than in non-responders (4.5 and 4 months, p=0.003 and p=0.008, respectively). Low-dose melphalan shows significant activity in high-risk MDS and AML with multilineage dysplasia with acceptable toxicity.

[Augmented activity of the adrenal medulla in young men with positive family history of essential hypertension]. / Zwiekszona aktywnosc rdzenia nadnerczy u mlodych mezczyzn z rodzinnym ryzykiem pierwotnego nadcisnienia tetniczego.

Serum adrenaline (AD) and noradrenaline (NA) were measured by RIA method in two groups of young males: group S (n = 54) with positive family history of essential hypertension (EH) and group K (n = 9) with negative family history of EH (mean age: 24.6 +/- 3.3 i 23.6 +/- 3.6 years respectively). AD and NA concentrations were estimated in basic conditions (AD1, NA1) and after 10 min of passive vertical posture(AD2, NA2). In group S AD1 concentration was higher than in group K (54.4 +/- 24.4 i 37.8 +/- 15.6 pg/ml respectively, p < 0.05). In group S a positive correlation was found between mean systolic blood pressure (SBP) and mean heart rate (HR) estimated during 5-hours monitoring by Spacelab IGR 5300 ambulatory blood pressure and heart rate monitoring system (r = 0.5, p < or = 0.01). Pearson's correlation coefficient (Pcc). In this same group positive correlations were also found between AD2 and SBP - r = 0.31, p < 0.05 (Pcc) and between AD2 and HR: r = 0.33, p < 0.05 (Pcc). Results of 5-hours blood pressure monitoring showed that 15 of 54 males from group S had SBP > 139 mmHg (group S1). In group S1, AD1 and AD2 concentrations were higher than in group K (AD1: 366 +/- 144; 206 +/- 85, p < 0.01 and AD2: 626 +/- 266; 369 +/- 156 fmol/ml, p < 0.05 respectively). No differences were found in AD1, AD2, NA1 and NA2 concentration between group K and normotensive (SBB < 140 mmHg) males with positive family history of EH: group S2. In young males with positive family history of EH, the elevation of blood pressure might be caused by an augmented activity of the adrenal medulla.

[Young men with a positive family history of hypertension have higher values in a circadian blood pressure profile]. / Mlodzi mezczyzni z wywiadem rodzinnego nadcisnienia tetniczego maja wyzsze wartosci dobowego profilu cisnienia.

Non-invasive automatic 24-h indirect monitoring of blood pressure was performed in two groups of young males - group S - 55 men with positive family history of essential hypertension (EH) (mean age 24.6 +/- 3.6 years) and group K - 11 men with negative family history of EH (23.5 +/- 3.7 years). Circadian blood pressure variations were studied in two-hour periods throughout 24 hours. The curves of the blood pressure profiles in groups S and K had similar shape. The mean systolic blood pressure estimated for each of the two-hour periods was higher in group S than in group K in the corresponding period. Mean diastolic blood pressure estimated for each of the two-hour periods was higher in group S than in group K in almost all periods of the daily activity. These results indicate that young males with positive family history of EH have higher blood pressure than young males with negative family history of EH. This stable disregulation of blood pressure is present not only during day-time activity but also during sleep.

[Correlations between catecholamines and prostaglandins in patients with primary arterial hypertension and pheochromocytoma in basic conditions and after administration of clonidine]. / Wspólzaleznosc miedzy katecholaminami i prostaglandynami u chorych z nadcisnieniem tetniczym pierwotnym i z guzem chromochlonnym w warunkach podstawowych i po klonidynie.

Authors assessed correlation between venous blood catecholamines and prostaglandins concentrations before and after inhibition of sympathetic activity by clonidine in patients with primary hypertension or pheochromocytoma. 30 patients with essential uncomplicated hypertension and 11 with pheochromocytoma underwent the study. The control group consisted of 6 healthy volunteers. Serum norepinephrine (NA), epinephrine (A), prostaglandins: PGE2 PGF2 alpha and prostacyclin metabolite -6-keto-PGF1 alpha were determined before and 3 hours after oral administration of 0.3 mg clonidine. Negative correlation was stated between basic serum norepinephrine and 6-keto-PGF1 alpha concentrations in patients with pheochromocytoma, which could indicate prostacyclin metabolism disorders during persistent hypercatecholaminemia . There was no correlation between catecholamines and prostaglandins during the inhibition of sympathetic activity in patients with pheochromocytoma as well as essential hypertension. The positive correlation was observed between changes in serum NA and PGF2 alpha levels in patients with borderline hypertension. Thus, one may suppose, that correlation between na excretion and vasoconstrictive PGF2 proved in acute experiments, becomes evident within the early stage of hypertension also during sympathetic activity inhibition.

[Thrombotic thrombocytopenic purpura successfully treated with plasma exchange]. / Zakrzepowa plamica maloplytkowa skutecznie leczona wymiana osocza.

This study is a presentation of a case of a 43 year old woman suffering from thrombotic thrombocytopenic purpura, the clinical course of which was complicated and in which no improvement was observed after fresh frozen plasma transfusions and treatment with steroids. The complete clinical and haematological remission was obtained only after intensive plasma exchange by therapeutical plasmapheresis.