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K Hamulyák

Publications and source records attributed to K Hamulyák.

At least 19 recordsLinked to original sources
PubMed2005

Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis.

Elevated levels of coagulation factor VIII:C (FVIII:C) are associated with an increased risk for venous and arterial thromboembolism. Whether relatives of patients with elevated levels of FVIII:C are also at increased risk for thrombotic disease is unknown. The objective was to determine the annual incidences of both venous and arterial thrombotic events in first-degree relatives of patients with elevated levels of FVIII:C and venous thromboembolism (VTE) or premature atherosclerosis. A retrospective study with 584 first-degree relatives of 177 patients with elevated levels of FVIII:C was performed. The level of FVIII:C was determined and relatives with elevated and normal levels of FVIII:C were compared. Of the participants, 40% had elevated levels of FVIII:C. The annual incidence of a first episode of VTE was 0.34% and 0.13% in relatives with elevated levels of FVIII:C and those with normal levels, respectively [OR 3.7 (95% CI 1.9-7.5)]. The absolute annual incidence in the youngest age group with elevated levels of FVIII:C was 0.16% (0.05-0.37) and gradually increased to 0.99% (0.40-2.04) in those older than 60 years of age, although the odds ratios were not statistically significant. The annual incidences of a first arterial thrombotic event were 0.29% and 0.14% in relatives with and without elevated levels of FVIII:C, respectively [OR 3.1 (1.4-6.6)]. In particular the risks for a first myocardial infarction [OR 4.3 (1.0-18.1); P =0.046] and a first peripheral arterial thrombosis [OR 8.6 (1.6-47.6)] were increased. Within families of patients with elevated levels of FVIII:C and VTE or premature atherosclerosis, 40% of their first-degree relatives has elevated levels of FVIII:C as well, and they are at increased risk for both VTE and arterial thrombosis as compared with their relatives with normal levels.

Adolescent↗
PubMed2004

Severity of venous insufficiency is related to the density of microvascular deposition of PAI-1, uPA and von Willebrand factor.

BACKGROUND: Impaired microcirculation in chronic venous insufficiency leads to chronic inflammation and dystrophic changes of the skin, and finally to leg ulceration. The purpose of this study was to investigate in more detail coagulation and fibrinolytic protein response of the capillaries in skin biopsies of the lower extremity. PATIENTS AND METHODS: From eighteen ambulant patients with venous leg ulcer(s) (n = 8) and controls (n = 10) with various degrees of venous insufficiency according to the CEAP classification, we obtained 4 mm punch biopsies. Immunohistochemical staining with tissue derived plasminogen activator (tPA), urokinase derived plasminogen activator (uPA), plasminogen activator inhibitor (PAI-1) and von Willebrand Factor (vWF) was performed and analyzed with bright field microscopy. RESULTS: The amount of staining with vWF (p = 0.04) and uPA (p = 0.02) showed statistically significant differences, PAI-1 (p = 0.09) and tPA (p = 0.50) showed no difference between leg ulcer and control groups. A strong proliferation of capillaries with tortuous capillary loops in the papillary dermis was seen, but no statistically significant difference (M-W test, p = 0.10) was found between the groups. Comparison between CEAP classes 0-6 showed a statistically significant increased staining pattern of vWF (p = 0.06), uPA (p = 0.02) and PAI-1 (p = 0.02), but not from tPA (p = 0.30). CONCLUSIONS: In skin biopsies of the lower extremity of patients with severe venous insufficiency increased deposition of vWF, PAI-1 and uPA were found in the capillaries. These findings point to a local imbalance in coagulation and fibrinolytic status, which might contribute to impaired microcirculation and finally to the development of venous leg ulceration.

Adult↗
PubMed2003

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.

Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K1 (1 mg/day) and a mineral + vitamin D supplement (8 microg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K1 (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35-3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10-3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.

Absorptiometry, Photon↗
PubMed2003

The prognostic value of the soluble urokinase-type plasminogen activator receptor (s-uPAR) in plasma of breast cancer patients with and without metastatic disease.

Elevated levels of soluble uPAR (s-uPAR) and other fibrinolytic parameters functionally related to the urokinase-type plasminogen activator system might indicate the presence of cancer cells. In 25 breast cancer patients with metastases s-uPAR was significantly increased compared with 25 patients without metastases and with 25 healthy controls: 420 pg mL-1 vs. 145 pg mL-1 (P = 0.005) and 190 pg mL-1 (P = 0.003). Plasmin-alpha2-antiplasmin (PAP) complexes and d-dimers were significantly increased in breast cancer patients with metastases compared with patients without metastases and with healthy controls. The levels of plasminogen activator inhibitor (PAI)-1 activity, uPA antigen and factor (F)XIIa did not significantly differ between the patient groups and healthy controls. PAP complexes (529 microg L-1 vs. 420 microg L-1; P = 0.03), d-dimers (278.5 ng mL-1 vs. 79.0 ng mL-1; P = 0.005) and FXIIa (1.64 ng mL-1 vs. 1.19 ng mL-1; P = 0.01) were significantly higher in patients with metastases not surviving compared with patients with metastases surviving the 3-year follow-up period. Plasma s-uPAR levels in the patients with metastases did not discriminate between patients surviving and patients not surviving after 3-year follow-up. No significant differences in s-uPAR or any of the other parameters were found in the five patients developing metastases during follow-up. A single value of s-uPAR is of limited value in the follow-up of breast cancer patients with and without metastatic disease and does not predict survival or future metastases.

Aged↗
PubMed2002

Recurrent leg ulcers in a young man with hyperhomocysteinemia, factor V Leiden and impaired fibrinolysis.

We present a young male patient referred to our hospital with leg ulcers on both legs that were more than 3 years refractory to standard treatment with compression therapy. By thrombophilia screening factor V Leiden mutation, hyperhomocysteinemia and evidence for impaired fibrinolysis were found. Treatment with folic acid in combination with long-term oral anticoagulant therapy was added to non-elastic compression therapy. The leg ulcers showed slow improvement and complete healing within 3 years. During a 6-year follow-up period neither new thrombo-embolic events occurred nor recurrence of ulcerations. This case suggests a potential synergistic pathogenic role of factor V Leiden, hyperhomocysteinemia and impaired fibrinolysis in the development of postthrombotic syndrome and his sequelae. We postulate that increased formation of thrombi in the microcirculation of the skin in combination with ambulatory venous hypertension due to recurrent deep venous thrombosis might explain our observation.

Adrenal Cortex Hormones↗
PubMed2001

Timing of initial administration of low-molecular-weight heparin prophylaxis against deep vein thrombosis in patients following elective hip arthroplasty: a systematic review.

BACKGROUND: Perioperative and postoperative venous thrombosis are common in patients undergoing elective hip surgery. Prophylactic regimens include subcutaneous low-molecular-weight heparin 12 hours or more before or after surgery and oral anticoagulants. Recent clinical trials suggest that low-molecular-weight heparin initiated in closer proximity to surgery is more effective than the present clinical practice. We performed a systematic review of the literature to assess the efficacy and safety of low-molecular-weight heparin administered at different times in relation to surgery vs oral anticoagulant prophylaxis. METHODS: Reviewers (A.F.M. and S.M.M.) identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies. Randomized trials comparing low-molecular-weight heparin administered at different times relative to surgery with oral anticoagulants in patients undergoing elective hip arthroplasty, evaluated using contrast phlebography, were selected. Two reviewers (A.F.M. and S.M.M.) extracted data independently. RESULTS: The literature review identified 4 randomized trials meeting predefined inclusion criteria. The results indicate that low-molecular-weight heparin initiated in close proximity to surgery resulted in absolute risk reductions of 11% to 13% for deep vein thrombosis, corresponding to relative risk reductions of 43% to 55% compared with oral anticoagulants. Low-molecular-weight heparin initiated 12 hours before surgery or 12 to 24 hours postoperatively was not more effective than oral anticoagulants. Low-molecular-weight heparin initiated postoperatively in close proximity to surgery at half the usual dose was not associated with a clinically or statistically significant increase in major bleeding rates (P =.16). CONCLUSIONS: The timing of initiating low-molecular-weight heparin significantly influences antithrombotic effectiveness. The practice of delayed initiation of low-molecular-weight heparin prophylaxis results in suboptimal antithrombotic effectiveness without a substantive safety advantage.

Administration, Oral↗
PubMed2001

A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism.

BACKGROUND: The factor V Leiden mutation is a common genetic defect associated with an increased risk for venous thromboembolism. The clinical implications for asymptomatic carriers of this mutation and, consequently, the usefulness of screening families in which a proband has both the mutation and venous thromboembolism are unclear. OBJECTIVE: To determine the incidence of venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation. DESIGN: Prospective cohort study. SETTING: University hospitals in the Netherlands. PARTICIPANTS: 470 asymptomatic carriers of the factor V Leiden mutation (234 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were homozygous. Carriers were identified by screening the first-degree relatives (>15 years of age) of 247 symptomatic probands. MEASUREMENTS: Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations. RESULTS: Nine venous thromboembolic events were observed in 1564 observation-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy. CONCLUSIONS: The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation is low and does not justify routine screening of the families of symptomatic patients.

Adolescent↗
PubMed2001

Activated protein C resistance during in vitro fertilization treatment.

Acquired resistance to the anticoagulant action of activated protein C (APC) has been proposed to explain the increased risk of venous thrombosis associated with pregnancy, hormone replacement therapy and the use of oral contraceptives. In this study, we have investigated whether the hormonal changes induced during in vitro fertilization (IVF) treatment are also associated with acquired APC resistance. Twenty-nine women, who were planned for an IVF cycle, donated blood at four time points during treatment, i.e. at baseline, down-regulation, hyperstimulation and luteal support. In the plasma samples, APC sensitivity ratios (APCsr) and the levels of progesterone and estradiol were measured. The changes in plasma concentrations of hormones were in accordance with literature. The APCsr increased significantly during hyperstimulation and remained high during luteal support. The extent of APC resistance occurring during IVF treatment was comparable to that observed during the use of second generation OC and was less pronounced than that occurring during pregnancy. The change in estradiol between baseline and hyperstimulation correlated with the change in APCsr. Although this suggests that plasma estrogen levels are an important determinant for acquired APC resistance, it remains to be established which plasma proteins are responsible for estrogen-induced APC resistance.

Activated Protein C Resistance↗
PubMed2001

Tissue factor activity in human monocytes is regulated by plasma: implications for the high and low responder phenomenon.

The 'high and low responder phenomenon' of monocyte tissue factor (MTF) activity has been attributed to effects on monocytes by granulocytes, platelets and lipopolysaccharide (LPS). To study the possible contribution of plasma to the high and low responder phenomenon, we measured the MTF activity in isolated cryopreserved human monocytes from two donors (monocytes A and monocytes B) after incubation in a plasma environment depleted of granulocytes, platelets and LPS. In buffer only, MTF activity was 643 and 679 fM (fM = final concentration of tissue factor), in normal pooled plasma, it was 1478 and 1615 fM (P = 0.001), respectively, in monocytes A and in monocytes B. Incubation with individual plasma samples from healthy controls (n = 43) gave a median MTF of 1355 fM (range 1044-1976 fM) and 1329 fM (range 858-1951 fM) respectively. A plasma consistently induced a higher or lower level of MTF activity in both monocytes: r = 0.82 (P < 0.00001). Coumarin use did not influence the high and low responder phenomenon. In the absence of granulocytes, platelets and LPS, plasma determines the high and low responder phenomenon. This phenomenon is not influenced by coumarin treatment.

Aged↗
PubMed2001

The risk of pregnancy-related venous thromboembolism in women who are homozygous for factor V Leiden.

The risk of venous thromboembolism (VTE) is increased in pregnancy and during the post-partum period. The absolute risk for pregnancy-related VTE in heterozygous women with the factor V Leiden mutation is approximately 2%, but studies on this risk for homozygous women show conflicting results. In a retrospective family study, we found that the risk of pregnancy-related VTE in women with a symptomatic first-degree relative was 17% per pregnancy (95%CI 4.7-37.4). Anticoagulant prophylaxis during the post-partum period appears to be indicated in asymptomatic homozygous women from symptomatic kindred, whereas this could be decided on an individual basis during pregnancy.

Factor V↗
PubMed2001

Effect of in vitro fertilization treatment and subsequent pregnancy on the protein C pathway.

Thirty-three women who were planned for an in vitro fertilization (IVF) cycle donated blood at four time points during treatment: at baseline, after downregulation, hyperstimulation and luteal support. Levels of progesterone, 17beta-oestradiol and indicators of the protein C pathway, i.e. activated protein C sensitivity ratios (APCsr), protein C, protein C inhibitor and protein S were measured. Compared with baseline, oestradiol decreased twofold at downregulation and increased 40-fold at hyperstimulation. Progesterone was elevated 2.5-fold at hyperstimulation and 40-fold at luteal support. The APCsr increased slightly at downregulation, significantly increased during hyperstimulation and remained high during luteal support. The plasma levels of the anticoagulant proteins did not change or changed moderately during treatment. During downregulation, progesterone correlated negatively with APCsr (r = -0.398, P = 0.024). At hyperstimulation oestradiol correlated with the APCsr (r =0.615, P < 0.0005). Moreover, there was a significant correlation (r = 0.599, P < 0.0005) between the difference in baseline and hyperstimulation values of oestradiol (Delta E2 = 6.6 nmol/l) and the APCsr (Delta APCsr = 0.30). Six women who participated in this study became pregnant. Compared with baseline, the APCsr was increased 1.9-fold (Delta APCsr = 1.48) and free protein S free level decreased 30% at 7 weeks of pregnancy. This study demonstrates that despite the considerable changes in endogenous oestradiol and progesterone during an IVF cycle, changes in plasma levels of anticoagulant proteins are moderate. The significant increase in the APCsr during hyperstimulation indicates that acquired APC resistance observed during sex steroid hormone changes in women is at least partially caused by high oestrogen levels. Our findings demonstrate that IVF treatment is accompanied by the development of a mild prothrombotic condition.

Activated Protein C Resistance↗
PubMed2001

Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis.

Factor V Leiden is the most common genetic defect associated with venous thromboembolism. Its clinical expression is limited and shows a wide intrafamilial and interfamilial variation, which might be explained by the influence of other genetic risk factors. We retrospectively studied 226 patients with factor V Leiden and documented venous thromboembolism (probands) and 400 first-degree carrier relatives to assess the contribution of concomitant genetic risk factors to the occurrence of venous thromboembolism. The prothrombin G20210A mutation was found in 8.3%, homozygosity of factor V Leiden in 7.2%, and inherited deficiencies of antithrombin, protein C or protein S in 4.7% of symptomatic carriers (probands and relatives), as compared with 6.0, 3.4 and 0.9% of asymptomatic carriers, respectively. The total follow-up time in relatives was 11 049 years. Prevalences of venous thromboembolism were 10.8% in single heterozygous factor V Leiden carrier relatives, 16.0% in double-heterozygotes for factor V Leiden and the prothrombin mutation, 36.8% in homozygotes for factor V Leiden, and 40.0% in double-heterozygotes for factor V Leiden and an inherited deficiency of protein C or protein S. Annual incidences in these groups were 0.39, 0.57, 1.41, and 4.76%, respectively. Multivariate analysis showed a small, non-significant additional effect of the prothrombin mutation on the risk of venous thromboembolism in heterozygotes for factor V Leiden [adjusted hazard ratio, 1.3; 95% confidence interval (CI), 0.5-3.8]. This effect was more pronounced for homozygosity of factor V Leiden (adjusted hazard ratio, 3.9; 95% CI, 1.7-9.0) and inherited protein C or protein S deficiencies (adjusted hazard ratio, 17.5; 95% CI, 3.8-81.2). Our data provide evidence of clustering of the evaluated genetic thrombophilic defects in symptomatic factor V Leiden carriers and support the assumption that the clinical expression of factor V Leiden depends on clustering in a part of carriers.

Adult↗