Search

The thalassamias are inherited disorders resulting from unbalanced synthesis of normal polypeptide chains of haemoglobins: of alpha chains in alpha-thalassemia and of beta chains in beta-thalassemia. In Poland, in contrast to beta-thalassaemia, there is no routine diagnostic approach to alpha-thalassaemia. In the present study, for detection of alpha-thalassemia we employed Multiplex-PCR (mPCR) and Multiplex Ligation-dependent Probe Amplification (MPLA). 48 patients with microcytosis and normal or decreased level of haemoglobin HbA2 were examined. In 10 patients three different kinds of deletion mutations in alpha-globin genes were detected: homozygotes and heterozygotes of -alpha(3.7) mutation (-alpha(3.7/-alpha(3.7) and -alpha(3.7)alpha alpha respectively), heterozygotes of Asian mutations (--SEA/alpha alpha), and a heterozygote of Mediterranean mutation (--MED alpha alpha). Our results demonstrate the usefulness of the combined methods of mPCR and MLPA in the diagnostics of alpha-thalassaemia.

Unlabelled: Surgery for malignant neoplasms in hemophilia patients is no different from standard procedures in the general population on condition that the normal hemostatic activity of deficient factors: VIII in hemophilia A and IX in hemophilia B in perioperative period is ensured. The aim of the study was to determine the type and frequency of malignant neoplasms in hemophilia patients as well as to provide a strategy for establishing safe hemostatic activity in surgically treated hemophilia patients., Material and Methods: In the period 2003-2008, surgical procedures were performed on 19 hemophilia A and B patients with diagnosed malignant neoplasms of various location. The following cases were diagnosed: 9 colorectal neoplasms, 2 pancreatic carcinomas, 2 larynx carcinomas, 1 stomach carcinoma, 1 liver, 1 nasopharyngeal, 1 testicle, 1 prostate and 1 skin. Seventeen patients were hemophilia A (6 severe, 4 severe with inhibitor, including 2 high titre and 2 low titre, 1 moderate and 6 mild) and 2 were hemophilia B (1 severe, 1 moderate). Patients mean age was 55.8 years (22-82). In factor-replacement therapy for patients with no inhibitor the strategy was to maintain the activity of the deficient clotting factor VIII before the operation at 80-100% of normal value, within the 80-100% range on the 1-3 day following surgery, at 60-80% on days 4-6, at 30-60% on days 7-10 day and at 20-40% on all subsequent days until the surgical wound healed. In hemophilia B patients the levels were about 20% lower. Deficient factor was injected every 8 or 12 hours or administered in continuous intravenous infusion. In hemophilia A patients with high titre inhibitors to factor VIII (above 5 Bethesda units/ml) activated prothrombin complex concentrates (aPCC)-FEIBA (Baxter AG) were used at 50-100 U/kg b.m., every 8-12 hours., Results: The nineteen patients with diagnosed malignant neoplasms (in the period 2003-2008) constituted 0.77% of the overall 2475 hemophilia patients entered into the National Registry Congenital of Hemorrhagic Diathesis. An overall number of 26 surgical procedures were performed in this group of 19 hemophilia patients including 20 procedures for malignant neoplasms and 6 for postoperative complications. All patients survived surgery. Two patients with pancreatic carcinoma died in the postoperative period due to multi-organ failure. Complications occured in 7 (37%) patients including 6 (32%) with bleeding complications: haemopneumothorax (n=1), intraperitoneal bleeding (n=2), abdominal parietal hematoma (n=1), hematuria (n=1), bleeding from esophago-pharyngo-cutaneous fistula following total laryngectomy (n=1). Other complications included: ileus (n=1), leakage of pancreato-jejunal anastomosis (n=1), dehiscence of abdominal wound (n=1) and bleeding from duodenal ulcer (n=1). These complications were successfully treated with surgery or endoscopy., Conclusions: Surgery of malignant neoplasms in hemophilia patients is burdened with a high risk of complications which include bleedings despite adequate replacement therapy and administration of factor eight by-passing concentrates in patients with high titre inhibitor. Therefore surgical procedures involving these patients should be performed in specialized centers with experienced team (surgeon, anaesthesiologist, haematologist) and supported by a laboratory for coagulation disorders.

Unlabelled: In the past, haemophilia replacement therapy was based on fresh frozen plasma, cryoprecipitate and blood transfusions--i.e. preparates not subjected to any viral inactivation methods. The aim of the present study was to assess the prevalence of HCV, HBV and HIV infections among Polish haemophiliacs., Materials and Methods: Severe haemophilia patients were divided into two age groups according to the type of replacement therapy used in the past: group 1--172 patients born 1935-1990, group 2--41 patients born 1991-2002. The following viral markers were tested: anti-HCV, RNA HCV (if needed--virus genotype), HBsAg and anti-HIV. In 75 patients / group 1 and 41 / group 2, anti-HBc presence was determined., Results: In group 1, 95% of patients were anti-HCV positive and in 77.3% RNA HCV was detected. The most prevalent was lb genotype (58.6%) followed by 3a (27%). HBsAg was found in 8.7% cases of group 1. Anti-HCV antibodies were detected in 51 of 75 (68%) patients of this group. One patient was anti-HIV positive. In only one patient of group 2 (2.4%) viral markers were detected (anti-HCV and RNA HCV)., Conclusion: Nowadays, the risk of HCV, HBV and HIV infection in Polish severe haemophiliacs is very low.

Acquired haemophilia (AH) is a severe bleeding diathesis that affects both males and females. It is caused by suddenly appearing autoantibodies that interfere with coagulation factor VIII (FVIII) activity. Although some conditions such as autoimmune diseases, cancer and puerperium seem likely to induce AH, in more than half of the observed cases autoantibodies to FVIII are idiopathic. The clinical picture is characterized by spontaneous and post-traumatic subcutaneous bleeds as well as massive mucosal membrane hemorrhages (from the genitourinary and gastrointestinal tracts). Typical abnormalities in AH are prolonged activated partial thromboplastin time and normal results of the other haemostatic tests (platelet count, prothrombin and thrombin times, fibrinogen concentration). Acquired haemophilia is definitely confirmed by quantification of FVIII neutralizing antibodies. Bleeds are usually treated with activated prothrombin complex concentrates and activated recombinant factor VII. In most patients with AH, the use of immunosuppressive agents results in autoantibody elimination and restoration of normal FVIII plasma activity.

Viruses GBV-C/HGV and TTV were identified in patients with hepatitis of unknown etiology. Aim of our study was to assess the frequency of infection markers of these viruses in blood donors and haemophilia patients treated with virucidaly activated and non inactivated blood products. Material and methods. TTV DNA (by PCR using primers to coding ORFI and non-coding region NC) and GBV-C/HGV (RNA by RT-PCR and anti-E2 by EIA) were tested in blood donors (200 for TTV and 219 for GBV-C/HGV), 122 haemophilia patients treated in the past with non inactivated blood products and in 20 haemophilia children treated exclusively with inactivated clotting preparations. Results RNA GBV-C/HGV were identified in 3,2%; 23,7% and in 0%, respectively blood donors, adult and children haemophilia patients. Antibody anti-E2 were found in 23,6%; 37% i 25% of studied groups respectively. DNA TTV was detected most frequently by NC than ORF1 primers: in 78% vs.10% of blood donors, 100% vs 43,5% of adult haemophilia patients and in 95% vs. 15% young haemophiliacs. Conclusions Haemophilia patients were at risk of GBV-C/HGV and TTV infection. Following implementation of viral inactivation methods in the process of clotting factor concentrates production, the risk for GBV-C/HGV transmission was significantly reduced and in less extant for TTV.

The aim of the present study was to describe the orthopaedic status of patients with severe haemophilia, and to relate this status to the type of replacement therapy received by patients prior to the study. Ninety two haemophiliacs with median age 26 were included. Six joints--knees, elbows and ankles were evaluated clinically using the Gilbert scale. The evaluation included physical status (0-12 points/joint) and pain score (0-3 points/joint). X-ray examinations were evaluated according to the Pettersson scale (0-13 points/joint). On all scales, normality was represented by 0 score. Knees were the most affected joints. Eighty four patients (91.3%) reported pain. Only one patient scored 0 on the Gilbert scale, and another on the Pettersson scale. Thirty seven percent of patients used orthopaedic equipment occasionally or constantly. Twenty five percent of patients had a history of orthopaedic surgery. Thirty eight percent were unemployed and received some form of social subvention. On demand treatment was applied. None of the patients received primary prophylaxis. The mean consuption of clotting factor concentrates was 68,054 IU per patient during the 12 months period prior to the current study. The results of this study indicate that vast majority of severe haemophilia patients in Poland above 20 are affected by haemophilic arthropathy. This disabling complication of severe haemophilia can be prevented only by introducing primary prophylaxis from the first years of life.

The aim of the study was to analyze the data on 3224 patients with inherited blood coagulation disorders registered in Poland till December 1st, 2003. In 2269 registered hemophilia patients, 1953 were hemophilia A, and 316 were hemophilia B. Hemophilia A occurs in 1512 families, and hemophilia B in 240 families. Severe hemophilia constitutes the majority of hemophilia A and B cases (59.7% and 56.6% respectively). About 50% of the hemophiliacs have no history of bleeding diathesis in the family. The mean age of hemophilia A patients is 30.9 years, and that of hemophilia B patients--29.2 years. Prevalence of hemophilia in Poland is approximately 1:12 300 inhabitants. Hemophilia A has been diagnosed in 60.6% of all patients with inherited blood coagulation disorders registered in Poland, von Willebrand disease-- in 21.9%, hemophilia B-- in 9.8% and factor VII deficiency-- in 3.3%.

Excessive menstrual bleeding is a common clinical problem in women of reproductive age. Hereditary bleeding disorders, such as von Willebrand disease, may be one of the causes of menorrhagia. The aim of our study was to assess the frequency of von Willebrand disease and other hemostatic defects in women with unexplained menorrhagia and without uterine pathology. Sixty-five women (mean age 31 +/- 8.7, range 18-48 years) presenting with menorrhagia were screened. An inherited bleeding disorder was diagnosed 9 (13.8%) patients; the disorders were von Willebrand disease of mild severity (type 1) in 8 cases (12.3%) and a platelet dysfunction (storage pool disease) in 1. The frequency of bleeding symptoms was higher in patients with an inherited hemostatic defect than in women without bleeding disorder. The results of this study underscore the need for hemostatic evaluation in women with excessive menstrual bleeding and without obvious pelvic abnormality.

The aim of the following study was to determine the prevalence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACL) in patients with a history of venous thromboembolism (VTE). The patient group comprised 218 subjects with VTE before the age of 45, recurrent VTE or thrombosis in an unusual site. The control group consisted of 218 age, and sex-matched healthy individuals. LA and/or ACL were detected in 19 among 218 patients (8.7%). Lupus anticoagulant was found in 17 patients with VTE and in none out of 218 controls. The odds ratio for having venous thromboembolism was 14.1 (95% CI: 1.8-108.8) for patients with LA. Lupus anticoagulant is significantly associated with VTE. The prevalence of anticardiolipin was similar in patients and in controls. The results of our study indicate that anticardiolipin antibodies are not associated with venous thromboembolism.

The G20210A mutation of the prothrombin (PT) gene has recently been identified as a risk factor for venous thromboembolism (VTE). This mutation was shown to be present mainly among Caucasian populations, with a higher frequency in southern than in northern Europe. The aim of our study was to determine the prevalence of the PT 20210A allele in the Polish general population and in patients with a history of venous thrombosis. The patient group comprised 323 subjects with VTE before the age of 45, recurrent VTE or thrombosis in an unusual site. The control group consisted of 399 healthy individuals. Heterozygosity for the PT 20210A allele was found in 21 (6.5%) patients and 7 (1.8%) controls. In 7 (33.3%) of the 21 heterozygous patients the PT 20210A allele was associated with the factor V Leiden mutation, in 1--with the homozygous C677T mutation of the methylenetetrahydrofolate reductase (MTHFR), and in 1--with lupus anticoagulant. Our results indicate that the presence of the 20210A allele is a mild risk factor for venous thrombosis if not associated with other thrombophilic defect (odds ratio 2.2; 95% CI: 0.8-5.5). The risk is greater in double heterozygous carriers of the PT 20210A allele and factor V Leiden mutation.

The development of antibodies to factor VIII (circulating anticoagulant, factor VIII inhibitor) is a serious complication following substitution therapy in patients with hemophilia A. These antibodies are rarely specific of human factor VIII, tending to cross-react to a variable extent with factor VIII from other species. Their neutralizing activity is usually weaker against porcine than human factor VIII. In this study, anti-human and anti-porcine factor VIII antibodies (Ab) were measured in 41 patients with severe hemophilia A. The anti-human Ab titers ranged from 0.5 to 1200 BU/ml, and the anti-porcine Ab titers ranged from 0 to 170 BU/ml. The median cross-reactivity was 28% (mean 28.9 +/- 17.2%, range 0-75%). Of the 24 patients with anti-human Ab titers > 5 BU/ml, 11 (46%) had a low anti-porcine Ab level (< or = 5 BU/ml). These patients could be treated effectively with porcine factor VIII concentrate (Hyate: C).