Polymorphisms in the factor VII gene and ischemic stroke in young adults.

Polymorphic configurations of the coagulation factor VII gene (F7) are associated with plasma levels of FVII antigen (FVII:Ag) and FVII coagulant activity (FVII:C). Our aim was to determine whether F7 polymorphisms influence risk of ischemic stroke in young adults. One hundred and fifty survivors of ischemic stroke before the age of 45 and an equal number of age and sex-matched controls were genotyped for five F7 polymorphisms: the -A670C transversion, -323 decanucleotide insertion (P + 10), the number (which varies between five and eight) of a 37 base pair repeat polymorphisms in intron 7 (IVS7), amino acid substitution R353Q, and +154AA insertion. 353Q, P + 10 and +154AA were demonstrated to associate with significantly decreased plasma FVII:Ag, whereas -670C and IVS7 seven or higher were associated with a tendency towards increased plasma FVII:Ag. The former three polymorphisms were significantly more common in control individuals than in patients, whereas the latter two were significantly more common in patients than in control individuals. The multiple logistic regression analysis revealed that two F7 polymorphisms, -670C and IVS7 seven or higher, are independent risk factors for ischemic stroke in young adult patients.

[GBV-C/HGV and TTV infection markers in Polish blood donors and haemophilia patients]. / Markery zakazenia wirusami GBV-C/HGV i TTV u chorych na hemofilif, oraz u dawców krwi w Polsce.

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.

Prevalence of the intron 22 inversion of the factor VIII gene and inhibitor development in Polish patients with severe hemophilia A.

INTRODUCTION: Patients with severe hemophilia A often develop inhibitors (antibodies) against transfused factor VIII. MATERIAL/METHODS: One hundred thirteen Polish patients with severe hemophilia A, who had been treated on demand with cryoprecipitate until 1992 and exclusively with factor VIII concentrates after 1995, were examined for intron 22 inversion by Southern blotting and the presence and magnitude of inhibitor activity in blood as determined by the Bethesda assay. The patients' ages ranged 4--67 years (mean: 33.7+/-12.4 years, median: 32 years). RESULTS: The number of patients with the inversion amounted to 57, while in 56 patients the mutation types were unknown; 47 patients had a distal and 10 patients a proximal type of inversion. Thirteen patients with inversions (22.8%) were found to have inhibitor in their blood. Most patients (14 out of 15) who developed inhibitors in the course of cryoprecipitate therapy were high responders. Conversely, 4 of 5 patients treated between 1992 and 1995 with both cryoprecipitate and intermediate-purity factor VIII concentrates were low responders. One multitransfused patient who had remained inhibitor-free on cryoprecipitate therapy developed inhibitor after receiving a large dose of factor VIII concentrate during surgery. None of these 5 patients developed inhibitors during their 12--40 years of treatment with cryoprecipitate, suggesting that it was less immunogenic than factor VIII concentrates. CONCLUSIONS: The prevalence of the intron 22 inversion mutation of the factor VIII gene in Polish hemophiliacs is similar to that in other European countries. Treatment regimens with either cryoprecipitate or virus-inactivated plasma-derived factor VIII concentrates may affect inhibitor formation in hemophilia A patients.

[The orthopaedic status of a selected severe haemophilia group]. / Stan narzadu ruchu w wybranej grupie chorych na ciezka hemofilie.

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.

Possible role of factor XIII subunit A in Fcgamma and complement receptor-mediated phagocytosis.

Besides its traditional role in hemostasis, factor XIII subunit A (FXIII-A) is supposed to function as a cellular transglutaminase and to be involved in certain intracellular processes, including cytoskeletal remodeling. To investigate its intracellular role, the aim of the present study was to follow changes in FXIII-A production in combination with the receptor-mediated phagocytic activities of monocytes/macrophages and to examine the phagocytic functions of monocytes in patients with FXIII-A deficiency. Human blood monocytes were isolated from the buffy coats of healthy volunteers and cultured for 4 days. The FcgammaR-mediated phagocytosis of sensitized erythrocytes (EA) and the complement receptor (CR)-mediated phagocytosis of complement-coated yeast particles were studied during monocyte/macrophage differentiation. Changes in the gene expression of FXIII-A were detected by real-time quantitative RT-PCR. FXIII-A protein production was investigated with fluorescent image analysis at single cell level and Western immunoblot analysis. Both the FcgammaR and CR-mediated phagocytosis increased during culturing, which peaked on day 3. The phagocytic activity of the cells could be markedly inhibited with monodansylcadaverine, an inhibitor of the transglutaminase-induced crosslinking of proteins. The phagocytosis of EA, complement-coated and uncoated yeast particles was found to be strongly diminished in monocytes of FXIII-A deficient patients. The phagocytic functions of cultured cells showed a change in parallel with the alterations in FXIII-A mRNA expression, as well as with that in FXIII-A in protein synthesis detected by image and Western immunoblot analyses in concert. Our results suggest that FXIII-A plays a role in the Fcgamma and complement receptor-mediated phagocytic activities of monocytes/macrophages.

[Von Willebrand disease in women with menorrhagia]. / Choroba von Willebranda u kobiet z krwotocznymi miesiaczkami.

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.

[Hemophilia and other inherited blood coagulation disorders in Poland]. / Hemofilia i pokrewne skazy krwotoczne w Polsce.

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%.