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Biomedical subjects

E F Mammen

Publications and source records attributed to E F Mammen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Preliminary data from a field trial of the PFA-100 system.

The PFA-100 system (Dade International Inc., Miami, FL) is a platelet function analyzer, the design of which is based on the technology of the Thrombostat 4000 VDG, Seeon, Germany. It was developed to measure primary, platelet dependent hemostasis in citrated whole blood in vitro. A first pilot study was conducted with the instrument to assess performance characteristics. Healthy subjects (normals) who had not ingested any medications, and patients (abnormals) with primary, platelet-related hemostasis defects, which included users of aspirin, were studied with two test cartridges; collagen/ADP and collagen/epinephrine. Before the study certain variables were tested that ascertained that blood drawn into either 3.8% or 3.2% sodium citrate containing vacutainers (rather than syringes) could be used for testing. Tests must be performed within a five-hour time span from drawing to testing, and blood must be kept at room temperature. Normal reference values were 77-133 seconds closure times for collagen/ADP and 98-185 seconds for collagen/epinephrine. Precision testing revealed a CV of < 10% for within-day and between-day (five days) analyses on collagen/ADP cartridges and a CV of 5-14% for both runs on the collagen/epinephrine cartridges. No clinically important differences were found between measurements in the two positions of the instrument, although one follows the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleeding Time↗
PubMed1994

Prothrombin fragment F 1 + 2 and oral anticoagulant therapy.

This study was undertaken to establish a correlation between prothrombin activation fragment F 1 + 2 and one-stage prothrombin time (PT) ratios in patients receiving oral anticoagulant therapy. One hundred consecutive patients on warfarin treatment were utilized for this study. The patients had received warfarin for not less than four days prior to entry into the study. F 1 + 2 levels and PT ratios were found to be 0.28 +/- 0.24 nM/L (mean +/- SD) ranging from 0.01 to 1.5 nM/L and 1.62 +/- 0.46 (mean +/- SD) ranging from 0.97 to 3.11, respectively. Most patients on oral anticoagulants with PT ratios between 1.2 - 1.7 exhibited decreased concentrations of F 1 + 2. Normal control values of F 1 + 2 were established for this study in 40 healthy individuals; they were 0.40 +/- 0.23 nM/L (median +/- SD) ranging from 0.11 to 1.19 nM/L. Mean plasma levels of F 1 + 2 were significantly lower in the anticoagulated patients as compared to the healthy controls (t = 2.377, p < 0.05). The relationship between F 1 + 2 levels and PT ratios in the 100 anticoagulated patients was analyzed by linear regression. No significant correlation (r = -0.208) was found between F 1 + 2 levels and PT ratios. It is concluded that the degree of reduction in F 1 + 2 levels is not proportional to the intensity of therapy reflected by the PT ratios in anticoagulated patients.

Administration, Oral↗
PubMed1994

Hemostasis and diagnosis of preeclampsia.

The diagnosis of preeclampsia, with all of its consequences, is at times difficult to establish, especially when the patient has underlying chronic hypertension and is not known from prior prenatal care visits. Many screening tests have been proposed. These should be sensitive, relatively specific, easy to perform, of low cost, and have a reasonable interval from prediction to disease onset. Laboratory assays would obviously be useful. We evaluated hemostasis tests for the diagnosis of preeclampsia, and compared fibronectin, antithrombin III and alpha 2-antiplasmin in 48 preeclamptics and 86 control nulliparas. Receive operator characteristic (ROC) curve analysis suggested that fibronectin is the most effective of these tests. A similar analysis comparing the results of previous studies using serum iron, angiotensin infusion, urinary calcium/creatinine ratio, the rollover test and uric acid suggested a possible role for fibronectin in the diagnosis of preeclampsia. While not ideal, there seems to be, at present, no other, easy to perform laboratory test that outperforms fibronectin in predicting preeclampsia.

Adult↗
PubMed1994

Coagulation defects in liver disease.

A normally functioning hemostasis system is closely related to liver function. The liver parenchymal cells produce most of the factors and inhibitors of the clotting and fibrinolytic systems, and the RES of the liver greatly aids in the clearance of activation products. Hemostasis defects thus depend on the extent of liver damage. A wide spectrum of defects is found in patients with liver cirrhosis. Owing to impaired protein synthesis, most factors and inhibitors of the clotting and the fibrinolytic systems are markedly reduced. Additionally, abnormal vitamin K-dependent factor and fibrinogen molecules have been encountered. Most patients have hyperfibrinolysis that could be DIC in nature. Thrombocytopenia and thrombocytopathy are also found. Acute or chronic hepatocellular disease may display decreased vitamin K-dependent factor levels, especially factor VII and protein C, with other factors still being normal. If patients go into hepatic failure, the abnormalities resemble those found in liver cirrhosis. Vitamin K deficiency is associated with the production of poorly functioning vitamin K-dependent factors. All other hemostasis parameters are normal. Disturbances associated with liver surgeries again depend on the underlying liver problem. Peritoneovenous shunts (LeVeen) may lead to DIC; bleeding from partially resected liver surfaces is usually a mechanical problem. Severe bleeding is encountered with orthotopic liver transplantation. It is greatly influenced by the activation of the fibrinolytic system. This occurs during the anhepatic phase and during the reperfusion phase. The hyperfibrinolysis is mediated by an intense release of t-PA. Antifibrinolytic drugs, if used cautiously, have markedly reduced bleeding and thus reduced need for blood and blood product substitution.

Blood Coagulation Disorders↗
PubMed1994

Coagulopathies of liver disease.

Disturbed liver parenchymal cell function adversely impacts on the hemostasis system, the extent of which correlates with the degree of liver disease. Because liver parenchymal cells synthesize most factors of the clotting and the fibrinolytic systems, levels of these procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic factors will decrease in plasma. These changes may be minor in patients with mild liver disease but are severe in patients with cirrhosis. Thrombocytopenia and thrombocytopathy usually complicate the clinical presentation, and systemic activation of the fibrinolytic system is always seen in cirrhotic individuals. Whether this fibrinolytic activation is primary or secondary in response to DIC is controversial. Some of the laboratory findings in DIC may be a reflection of decreased hepatic clearance of activation products by the reticuloendothelial system of the diseased liver. In patients with vitamin K deficiency or in those receiving oral anticoagulants, only the vitamin K-dependent procoagulants and anticoagulants are altered; all other parameters remain in the normal range. Laboratory changes associated with various surgical interventions involving the liver depend on the underlying pathology. Severe hemorrhages are encountered during orthotopic liver transplantation. During the anhepatic phase and during the reperfusion phase, there is a major activation of the fibrinolytic system. It is unclear whether this fibrinolytic response is primary or secondary. The use of antifibrinolytic agents has markedly reduced the clinical bleeding and, thus, the requirement for blood and blood products. Bleeding associated with partial liver resection is usually mechanical in nature, but peritoneovenous shunt operations can result in DIC. Ascites fluid is the trigger. The injection of thrombin containing sclerosants can also activate the hemostasis system in vivo, although, generally, no clinically detectable adverse reactions are noted.

Acute Disease↗
PubMed1993

Thrombin increases the metastatic potential of tumor cells.

Initial arrest of tumor cells in the microvasculature and their attachment to the endothelium and subendothelial matrix (SEM) are essential prerequisites for metastasis to occur. Factors mediating these interactions are viewed as important determinants of the tumor-cell metastatic phenotype. In this work we have studied the effects of thrombin, its analogs and its precursors on the adhesive properties and metastatic potential of tumor cells. We show that alpha-thrombin, the native form of the key coagulation enzyme, is capable of enhancing tumor-cell adhesion to both the endothelium and SEM components represented by fibronectin. Subclotting, physiological concentrations of alpha-thrombin produced a 2- to 5-fold increase in tumor-cell adhesion. A bell-shaped dose-response curve was observed, with maximal effect at 0.1 U/ml. Maximum effect occurred when cells were exposed to the agonist for 15 min and exposure for up to 4 hr resulted in enhanced tumor-cell adhesion. Prolonged incubation with thrombin resulted in a decline in the thrombin-enhanced adhesion which reached unstimulated control levels by 24 hr. Thrombin precursors and active-site-inhibited thrombin analogs only had minimal adhesion-enhancing activity; nitro- and exosite-alpha-thrombin, which retain a functional active site, mimicked, although to a lesser degree, the action of alpha-thrombin. Tumor-cell incubation with thrombin resulted in an upregulated cell-surface expression of the alpha11b beta 3 integrin, a receptor mediating interactions between tumor cells and endothelial cells, and between tumor cells and SEM. Antibodies against alpha 11b beta 3 integrin effectively inhibited thrombin-enhanced tumor-cell adhesion. Thrombin effects on tumor cells involved the PKC signal transduction pathway as thrombin-enhanced adhesion was inhibited by pre-incubation with PKC inhibitors and a transient PKC translocation from cytosol to membrane was observed following thrombin challenge. In vivo, thrombin-treated tumor cells demonstrated a 2-fold increase in their lung-colonizing ability. In contrast to the adhesion results, the metastasis-enhancing effects of alpha-thrombin were mimicked by a thrombin precursor (prothrombin) and thrombin analogs.

Animals↗
PubMed1993

Perspectives for the future.

The pathophysiology of sepsis and septic shock is extremely complex and ultimately involves every physiological pathway. The initiating event is the entrance of endotoxin or similar substances into the blood which initiates the release of multiple mediators. These are designed to react locally and to protect the organism. Their constant release, however, sets in motion up- and down regulations, ultimately resulting in "metabolic anarchy". Tumor necrosis factor alpha and other cytokines trigger several systems, especially coagulation to yield DIC, and the complement system. Many treatment modalities have been developed, most recently those which substitute inhibitors of various systems. Antithrombin III concentrates and potentially protein C concentrates are designed to arrest DIC. C1-esterase inhibitor concentrates should intercept the activation of the complement system and the contact phase of coagulation and its relationship to kinin generation. Even newer approaches entail antibodies to tumor necrosis factor alpha or endotoxin itself. The complex process of sepsis will undoubtedly require a multifaceted therapeutic approach.

Antibodies, Monoclonal↗
PubMed1993

Fibrinolytic parameters in women undergoing ovulation induction.

OBJECTIVE: The purpose of this study was to evaluate the effect of elevated levels of circulating estradiol on the clotting and fibrinolytic system in patients undergoing controlled ovarian hyperstimulation. STUDY DESIGN: Fifty-two patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins or urofollotropin were asked to participate. Blood for hemostasis parameters was obtained on the days that patients returned for estradiol sampling. Sample days were identified as cycle days 1 to 5 (baseline), 6 to 9, and 10 to 14. Each factor was analyzed by repeated-measures analysis of variance and correlation analysis. RESULTS: A significant decline was observed for tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity from baseline to cycle days 10 to 14. As serum estradiol levels increased throughout each phase (maximum mean estradiol 739.8 pg/ml), a significant linear decrease was observed for both tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity, whereas thrombin-antithrombin III complexes did not change significantly. A significant positive correlation was also observed for plasminogen activator inhibitor activity and tissue plasminogen activator antigen level over all cycle days examined. CONCLUSION: Down-regulation of the fibrinolytic system was observed as estradiol levels increased. However, thrombin formation did not change, thus suggesting that elevated circulating estradiol alone does not predispose to a thromboembolic event.

Adult↗
PubMed1993

Thrombosis and hormone replacement therapy in postmenopausal women.

OBJECTIVE: The effects of postmenopausal hormone replacement therapy on thrombosis remain controversial. We tested the hypothesis that estrogen or progesterone has no significant effect on thrombosis by means of newly developed markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin generation. STUDY DESIGN: A prospective study that included 106 women, 68 postmenopausal women on hormone replacement therapy and 38 postmenopausal controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured by enzyme-linked immunosorbent assay. Multivariate analysis of the covariance was used for statistical analysis, controlling for patient's age because the hormone replacement therapy group was older. RESULTS: There were no statistically significant differences between the hormone replacement therapy and control groups in either of the clotting parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex in patients receiving estrogen alone or estrogen plus progestin also revealed no differences. CONCLUSIONS: Current doses of postmenopausal hormone replacement therapy do not appear to enhance in vivo clotting. Thromboembolic complications among postmenopausal women receiving hormone replacement therapy may therefore be secondary to congenital or other acquired coagulation defects.

Adult↗
PubMed1993

Determination of low-molecular-weight heparin by Heptest on the automated coagulation laboratory system.

The manual Heptest for measuring low-molecular-weight heparin fractions was applied to a fully automated, coagulation-dedicated analyzer, the Automated Coagulation Laboratory 300 Plus. The clot-based assay mode of the instrument was used, which operates on the principle of light scattering. Undiluted plasmas and the original reagents of the Heptest kit were used. Also, the 2-minute incubation time of the manual procedure was maintained. Automation reduced plasma and reagent volumes by about one half. As a result of the high precision of the automated procedure, single determinations suffice, and 18 plasma samples can be analyzed in about 8 minutes. Coefficients of variation were 1.0% to 3.2% for within-run and 1.9% to 6.0% for inter-run analyses. Analytical recovery was 98% to 104%. Comparisons of 132 samples between the two procedures yielded an R value of 0.974 for activity expression in seconds and 0.945 for U/mL. Several low-molecular-weight heparin fractions were tested.

Blood Coagulation Tests↗
PubMed1993

Alpha 2-antiplasmin deficiency. An overlooked cause of hemorrhage.

PURPOSE: Alpha 2-Antiplasmin (AP) deficiency is a rare congenital bleeding disorder that presents with normal screening tests for platelet function and clotting. We believe that this disorder is frequently overlooked, especially in women with unexplained bleeding. PATIENTS AND METHODS: We report on two families and one single patient with heterozygous AP deficiency. RESULTS: All patients and most relatives with the defect had a mild bleeding tendency. CONCLUSIONS: We suggest the incorporation of the AP assay in all patients who have a bleeding disorder with normal platelet studies and normal clotting profiles.

Adult↗
PubMed1992

Thrombosis in spinal cord injury.

Some traditional coagulation assays and several new molecular markers of hemostatic activation were measured in 37 patients with spinal cord injury (SCI). Twenty one of the patients (57%) developed deep vein thrombosis (DVT). The radiofibrinogen uptake test (RFUT) was used to diagnose DVT. Thirty eight percent of quadriplegic and 88% of paraplegic patients developed DVT (p < 0.005). No significant differences were found in platelet counts, mean platelet volumes, fibrinogen levels, von Willebrand factor (Ag) levels, platelet factor 4 and beta thromboglobulin concentrations between the groups with and without DVT. Fibrinopeptide A, thrombin/antithrombin III (TAT) complexes and plasma D-dimer levels were significantly higher in the patients with thrombosis. Most patients with DVT had elevated TAT complex levels up to three days before the RFUT became positive. D-dimer levels were highest after the diagnosis had been made.

Adolescent↗
PubMed1992

An in vitro evaluation of the effect of laser irradiation on the thrombogenicity of thrombus.

The effect of laser irradiation on the thrombogenicity of thrombus was evaluated by treating thrombi, formed in-vitro from canine blood, with two different doses of cw Nd:YAG laser energy at 1064 nm. The thrombi were then incubated with whole blood, and the plasma levels of fibrinogen and thrombin-antithrombin III-complexes were measured. A statistically significant decrease (p < 0.05) in the thrombogenicity was indicated by a reduction in both fibrinogen consumption and levels of thrombin-antithrombin III-complexes in the high dose group (600 joules, 100 degrees C peak temperature) in comparison to the low dose group (300 joules, 70 degrees C peak temperature) and the untreated thrombi. These findings suggest that laser irradiation of thrombus at an appropriate dose may substantially reduce its thrombogenicity and ability to modulate hemostasis.

Animals↗