Warfarin use in hemodialysis patients: what is the risk?

BACKGROUND: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. METHODS: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. RESULTS: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). CONCLUSIONS: This study confirms the higher bleeding risk associated with HD/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. SUMMARY: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A secondary finding was that INR variability was significantly higher in HD patients than non-HD patients on warfarin.

Intracranial haemorrhage as initial presentation of severe haemophilia B: case report and review of Mayo Clinic Comprehensive Hemophilia Center experience.

A neonate who had intracranial haemorrhage (ICH) at birth received a diagnosis of severe haemophilia B at 6 months of age. ICH had been the initial presentation of his bleeding disorder. His family history was negative for haemophilia. Review of our institutional experience as well as the literature indicates that intracranial bleeding as the initial presentation of haemophilia is rare.

Haemorrhage into a popliteal cyst: an unusual complication of haemophilia A.

A 7(1/2)-year-old boy with severe haemophilia A had increasing discomfort and pain in his left knee after sledding on ice and landing on his knees. Left knee pain persisted for days despite recombinant factor VIII replacement. Imaging studies showed that by day 10 a popliteal cyst had ruptured, with diffusion of blood into the calf muscles. This case illustrates another possible bleeding complication in patients with a bleeding disorder and a popliteal cyst.

[Predictive features of positron emission tomography after two cycles of induction therapy in malignant lymphoma]. / Prediktivní vlastnosti pozitronové emisní tomografie provádené po druhém cyklu indukcní terapie maligních lymfomu.

BACKGROUND: Positron emission tomography (PET) is a modern functional imaging method, recently introduced to clinical oncology. The aim of our study was the evaluation of prognostic value of PET performed in malignant lymphoma patients after two cycles of chemotherapy. METHODS AND RESULTS: From 9/99 to 11/00 PET was performed in 37 patients with malignant lymphoma (9x m. Hodgkin, 21x HG + IG-NHL, 7x LG-NHL; 26x new diagnosis, 11x relaps of disease). Freedom from progression interval (FFP) and overall survival (OS) were evaluated. Attenuation corrected PET imaging was done by dedicated ECAT EXACT PET scanner from base of the skull to the upper thighs 1 hour after intravenous administration of 18-FDG (7.6 +/- 1.3 MBq/kg). Statistical analysis was done using Kaplan-Meier method. Significance of differences between groups was determined by log-rank test on the level of 5%. After the induction therapy, 30 patients were in complete remission, 3 patients in partial remission and in 4 cases progression of disease were observed. Progression of disease was seen in 4 patients. Median follow up of living patients was 7 months (1-13 months) from the end of therapy. Progression, resp. relapse of disease occurred in 13 patients during this period, two patients died. PET performed after the second course of therapy was positive in 18 patients and negative in 19 patients. Two progressions, resp. relapses of disease were documented in PET-negative group and 11 in PET-positive group. FFP was significantly different in PET positive and PET negative groups (p < 0.05). The negative and positive predictive values of PET for malignant lymphoma relapse or progression were estimated 89%, 63% respectively. CONCLUSION: Regardless the short follow-up period, our preliminary results reflect very good prognostic value of PET performed after the second course of chemotherapy in malignant lymphoma patients.

[Positron emission tomography (PET) in patients with malignant lymphomas--indications for the method as presented in case reports]. / Vyuzití pozitronové emisní tomografie (PET) u nemocných s maligními lymfomy--indikace metody prezentované formou kazuistických sdelení.

Positron emission tomography is a modern functional imaging method recently available also in the Czech Republic. The authors try to present indications of this method in the form of case-histories of patients with malignant lymphomas.

Antiemetic efficacy of three serotonin antagonists during high-dose chemotherapy and autologous stem cell transplantation in malignant lymphoma.

The aim of this study was to compare antiemetic efficacy of three serotonin antagonists, granisetron, tropisetron and ondansetron, during conditioning for autologous stem cell transplantation (ASCT). Forty-five malignant lymphoma patients (mean age 38 years, M:F 30:15), undergoing the highly emetogenic regimen BEAM prior to ASCT, were randomized to receive IV granisetron (G) 3 mg once a day, IV tropisetron (T) 5 mg once a day, or IV ondansetron (0) 8 mg twice daily, for six days. The treatment groups were comparable with respect to age, sex and previous experience of nausea and/or vomiting. Nausea and/or emesis control failure was defined as a nausea lasting > or = 4 hours and/or > or = 3 episodes of vomiting/24 h, emesis control failure as > or = 3 episodes of vomiting/24 h. Both the period of chemotherapy (6 days) and the whole period of observation (10 days) were evaluated. Nausea and/or emesis control failure occurred in 24% of patients during the period of chemotherapy and in 51% of patients throughout the whole period of observation, while emesis control failed in 2% and 27% of patients, respectively. The efficacy of three serotonin antagonists was comparable during the chemotherapy period (5 patients with nausea and/or emesis control failure in the granisetron group, 2 in the tropisetron group and 4 in the ondansetron group,p = 0.40). When evaluating the whole period of observation, the antiemetic response to G and T was significantly better than to O, nausea and/or emesis control failure having occurred in 7 (47%) patients treated with G, 5 (33%) patients treated with T, and 12 (80%) patients treated with O, p = 0.03. The results concerning emesis control failures were similar, G 4 (27%), T 1 (7%), O 7 (47%), p = 0.04. Headache was the only frequent side effect of serotonin antagonists (30% incidence). All three serotonin antagonists sufficiently controlled nausea and vomiting during high-dose chemotherapy (BEAM) administration in 67-87% of patients. In comparison with ondansetron, both tropisetron and granisetron proved to be more effective after ASCT, when emetogenic factors other than chemotherapy alone participated.

[Separation of hematopoietic progenitor cells from peripheral blood in patients with hemato-oncologic malignancy]. / Separace hemopoetických progenitorových bunek z periferní krve (PBPC) u pacientu s hematoonkologickými malignitami.

BACKGROUND: Transplantations of haematopoietic progenitor cells from peripheral blood (PBPC) are able to ensure haematopoietic and immunological reconstitution as well as stable long term engraftment. Autologous PBPC are administered after previous myeloablative chemotherapy to patients with haematological and non-haematological malignancies. The objective of the submitted study was to follow-up the results of autologous separations of PBPC in patients with a good effect of mobilisation therapy. The authors evaluated in PBPC concentrates the content of cell parameters needed for transplantation. In the subsequent part of the trial they mention the times of engraftment after autologous transplantation. METHODS AND RESULTS: The authors evaluated parameters of 26 separations of PBPC in 11 haematooncological patients with a good effect of mobilisation therapy and with concentration of CD 34+ cells higher than 20 x 10(3)/ml of peripheral blood. The separations of PBPC were implemented on the Cobe Spectra and Baxter CS 3000 Plus equipment under a standard regime with processing of 12 l blood, i.e. 2.7 total blood volumes of the patients. In the mentioned group of patients already from one separation an adequate amount of CD 34+ cells for their transplantation was obtained. Transplantation doses were prepared on average from two separations and amounted as regards MNC/kg, CD 34+ cells/kg and CFU-GM/kg to 4.3 x 10(8), 17.1 x 10(6) and 2.5 x 10(4). The assembled parameters correspond to, or in some parameters exceed, recommended amounts for their transplantation. CONCLUSIONS: In well mobilised patients under the regime of standard separations adequate amounts of progenitor cells for their autologous transplantation were obtained. Transplantation doses were prepared from two collections. Investigation of pre-separation concentration of CD 34+ cells in the peripheral blood is a reliable indicator for starting PBPC separation. Early post-transplantation results indicate the time of engraftment 10 days on average and minor need of substitution therapy with blood products.

[Effect of clodronate in patients with multiple myeloma. Evaluation of specific markers of bone resorption]. / Ucinek klodronátu u pacientu s mnohocetným myelomem. Hodnocení specifickými markery osteoresorpce.

BACKGROUND: In adjuvant therapy of patients with multiple myeloma among others anti-absorption properties of bisphosphonates are used. The objective of the present investigation was to evaluate the effect of long-term oral treatment route clodronate on the bone metabolism in this condition. As markers of bone reabsorption, assessment of pyridinoline and deoxypyridinoline in urine was used. METHODS AND RESULTS: We investigated in an open clinical trial 22 patients with multiple myeloma with bone changes confirmed on X-ray who had a normal calcium and creatinine serum concentration: the control group (A) comprised 13 patients (mean age 59 years, range 38-74 years), the experimental group (B) 9 patients (mean age 54 years, range 42-60 years). The patients in both groups were treated by chemotherapy, to group B concurrently clodronate 3 x 800 mg was administered by the oral route. No statistically significant differences were found between the two groups during the mean follow up period after assessment of the diagnosis (27 vs. 40 months) nor in the clinical stage of the disease. After intervals of 0, 3 and 12 months the excretion of pyridinoline and deoxypyridinoline in urine was assessed by liquid chromatography. At the same time also other parameters of osteoresorption were assessed (urinary calcium and hydroxyproline excretion). At the onset of the investigation the pyridinoline and deoxypyridinoline excretion in groups A and B did not differ statistically (pyr; 120.63 +/- 23.76 vs. 136.23 +/- 22.13 mumol/mmol creatinine. d-pyr: 19.61 +/- 3.65 vs. 22.76 +/- 5.40 mumol/mmol creatinine). After three months in group B a statistically significant drop of excretion of both metabolites was recorded (pyr. to 84.11 +/- 38.67 mumol/mmol creatinine, d-pyr. to 15.23 +/- 6.10 mumol/mmol creatinine). Their significantly reduced excretion persisted also after one year (pyr. 85.52 +/- 60.96 mumol/mmol creatinine, d-pyr. 12.6 +/- 6.56 mumol/mmol creatinine). CONCLUSIONS: Using specific markers, pyridinoline and deoxypyridinoline, the authors proved the favourable effect of long-term administration of clodronate on the bone metabolism in patients with multiple myeloma.

[Renal impairment in monoclonal gammapathies. Clinical study]. / Postizení ledvin u monoklonálních gamapatií. Klinická studie.

BACKGROUND: Renal involvement is an important and frequent complication in patient with monoclonal gammapathy (MG), especially in multiple myeloma (MM). Light chain proteinuria produces many renal manifestations, the most serious form is acute renal failure, which occurs in 5-10% of patients with MM. The frequency and form of renal involvement was determined in a group of patients with MG. The disturbances observed were correlated with the concentration and type of paraprotein in serum and urine. METHODS AND RESULTS: We investigated 82 patients, 37 men and 45 women with an average age of 63.5 years. Apart from standard nephrologic tests the aminoaciduria/24 h and urine acidification capacity was determined. In some patients renal biopsy was performed. Proteinuria was observed in 66 cases (80.5%), in 54 of them of Bence-Jones type. Nephrotic syndrome developed in 4 patients, in all cases the renal amyloidosis was present. Renal insufficiency was diagnosed in 39 patients (47.5%), mostly in MM. In 14 cases was renal insufficiency reversible, in 14 remain stable and in 11 progressed during the course of disease. Irreversible progression developed in terminal phase of disease in most cases. Acute renal failure was observed in 6 patients, only in four of them further course of renal disease could be evaluated. In half of these 4 patients the renal failure was reversible. CONCLUSIONS: Higher frequency of proteinuria and renal insufficiency was detected in patients with light chain paraprotein of lambda type, or biclonal kappa+lambda type. Aminoaciduria was diagnosed in 40% of patients, we did not observe complete Fanconi's syndrome. Incompleted form of renal tubular acidosis we diagnosed in 52% of cases without other signs of renal involvement.

Effective peritoneal therapy of acute pancreatitis in the rat with glutaryl-trialanin-ethylamide: a novel inhibitor of pancreatic elastase.

The six hour peritoneal lavage with glutaryl-trialanin-ethylamide, a low molecular competitive inhibitor of pancreatic elastase (IC50-8 mumol/l), effectively suppresses the evolution of taurocholate induced acute pancreatitis in the rat. The lavage alone is followed by a marked decrease of fat necrosis and amylase and lipase activity in serum. The area of pancreatic haemorrhage was significantly reduced only after the lavage solution was supplemented with Glt-Ala3-NHEt. The effect was not enhanced by a bolus injection of the inhibitor before starting the lavage. The combination of Glt-Ala3-NHEt with aprotinin or nafamstate mesilate produced only marginal greater benefit. The effect of Glt-Ala3-NHEt on pancreatic haemorrhage is time and dose related even with delayed onset of the lavage. Animals treated with peritoneal lavage without Get-Ala3-NHEt lived longer than controls (p less than 0.05), but by 60 hours the survival rate of both groups was almost the same (76 v 74%). All animals lavaged with Glt-Ala3-NHEt survived 120 hours and the difference in the survival rate between this and both remaining groups was significant (100% v 76% v 74% - p less than 0.05). The results were considered favourable and preliminary clinical trials of Glt-Ala3-NHEt in subjects with acute pancreatitis justified.

[Role of free oxygen radicals in the pathogenesis of internal diseases]. / Uloha volných kyslíkových radikálu v patogenezi nekterých interních onemocnení.

In the organism a part of molecular oxygen is converted into highly reactive radicals (superoxid, hydroxyl radical), which react with biological structures (proteins, nucleic acids, membranes). It is one of the general mechanisms of tissue damage, which occurs e. g. in ischemic reoxygenation, i. e. following intestinal, myocardial infarction; further in the site of inflammation the macrophages release superoxid extracellularly; in acute pancreatitis; in oxygenotherapy and other pathologic conditions. In all tissues there exists a protective system which, under physiological conditions, inactivates the toxic radicals. Enzymes (superoxid dismutase, physiological conditions, inactivates the toxic radicals. Enzymes (superoxid system, alpha-tocopherol, ascorbic acid are part of this system. The concept of tissue damage by radicals enables a new view on etiopathogenesis of some diseases and leads to endeavour to use the acquired knowledge in human medicine.

[Differentiation of pancreatic lipase and pseudolipase serum activity]. / Rozlisení aktivity pankreatické lipázy a pseudolipázy krevního séra.

The determination of the serum lipase activity by turbidimetric assay was modified and false-positive results due to pseudolipase presence were eliminated. The new method includes a preincubation with beta-mercaptoenthanol and its conditions are specified to use with kinetic analysers as LKB 2086. By using our new method we estimated the activity of the pseudolipase in 36.4% of the group of 85 patients with elevated serum lipase activity determined by standard turbidimetry. By introducing our differential method with beta-mercaptoethanol correction the increasing correlation about 27% between lipase activity and serum alpha-amylase activity was estimated.

Isolation and analysis of peptidic fragments of alpha-gliadin using reversed-phase high-performance liquid chromatography.

Peptidic fragments of alpha-gliadin were obtained by peptic-tryptic-pancreatic (PTP) digestion of the alpha-gliadin fraction isolated by ion-exchange chromatography on a sulphopropyl-Sephadex C-50 column. The proteolytic digest was fractionated by ultrafiltration into three subfractions, PTPa1-PTPa3. The subfraction PTPa2 was then analysed and individual peaks were separated using reversed-phase high-performance liquid chromatography (RP-HPLC) using a gradient of acetonitrile in 0.1% trifluoroacetic acid and a Separon SGX-C18 sorbent. A 100-mg amount of the PTPa2 subfraction was separated in a single analysis by preparative RP-HPLC and twenty peaks were obtained for further characterization. The molecular mass in range 300-3000 was established for individual peptidic fragments by gel-permeation chromatography on a TSK-G2000 SW column.

Effect of new oligopeptide inhibitors of elastase on acute experimental pancreatitis in the rat.

Acute experimental pancreatitis was induced in male Wistar rats by retrograde injection of 0.4 ml 2% sodium taurocholate into the common choledochopancreatic duct. Prophylactic intraperitoneal injection of 20 mg glutaryl-trialanine-ethylamide, Glt-(Ala)3-NH-Et, 30 min. before induction of pancreatitis reduced the amount of fat necroses and the activity of amylase and lipase in ascites. Repeated intraperitoneal injection of this inhibitor decreased pancreatic hemorrhage. Simultaneous administration of 20 mg Glt-(Ala)3-NH-Et intraperitoneally, and 10 000 KIU of aprotinin intravenously was followed by the most extensive inhibitory effect. Prophylactic and repeated administration of both inhibitors also reduced the area of pancreatic hemorrhage. The same mode of administration of 20 mg undecenoyl-aspartyl-dialanyl-proline-ethylamide, UDE-Asp-(Ala)2-Pro-NH-Et, intraperitoneally and 20 000 KIU of aprotinin intramuscularly, resulted in selective inhibition of fat necroses in all localizations. Glt-(Ala)3-NH-Et and UDE-Asp-(Ala)2-Pro-NH-Et are considered effective inhibitors of various macroscopic and biochemical signs of acute pancreatitis in the rat during short-ferm experiments, if administered prophylactically or early after induction of the disease.