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Biomedical subjects

E F Mammen

Publications and source records attributed to E F Mammen.

At least 19 recordsLinked to original sources
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↗
PubMed1992

LMW heparin (anti-Xa) assays for clinical monitoring and pharmacokinetic studies on the automated coagulation laboratory (ACL).

Chromogenic anti-Xa activity procedures were developed for monitoring LMW heparins on the Automated Coagulation Laboratory 300 Plus (ACL, Instrumentation Laboratory) system. For daily monitoring, a "Routine" procedure was devised which allows accurate measurements between plasma levels of 0.1 and 1.0 u/ml LMW heparin. For lower levels a "Routine-Low" method was developed which assesses activities between 0.05 and 0.4 u/ml. Due to variabilities in dODs of individual baseline plasmas, levels below 0.05 u/ml might be inaccurate when pooled normal plasma is used to establish the reference curve. While levels less than 0.05 u/ml should rarely be encountered when monitoring LMW heparins for routine clinical use, pharmacokinetic studies require accurate measurements below that level. For this reason a "Research-High" and a "Research-Low" procedure was designed. For these procedures a study subject's own baseline plasma was used to establish the reference curve. The "Research-High" measures activities between 0.4 and 2.0 u/ml, the "Research-Low" between zero and 0.4 u/ml. The procedures have excellent within-run and inter-run coefficients of variation (less than 5%) and high levels of accuracies. Even inter-instrumental reproducibilities are less than 10%. Different manufacturers' LMW heparins can be analyzed by these assays. The procedures offer full automation, great cost-effectiveness due to lower reagent volumes, rapid turn-around time and great accuracy and reproducibility.

Antithrombin III↗
PubMed1992

Circadian variation in platelet function in healthy volunteers.

Circadian variation in hemostatic factors may contribute to a higher frequency of cardiac events observed in the morning and with activity. Diurnal changes in these factors were investigated by measuring in vitro platelet aggregability in response to epinephrine and adenosine diphosphate together with beta-thromboglobulin and platelet factor 4 as indexes of in vivo platelet activation. Activation of coagulation was measured by thrombin-antithrombin III complexes and D-Dimers. Tests were performed in 9 normal healthy subjects. Circadian changes occurred in beta-thromboglobulin (p less than 0.05) and platelet factor 4 (p less than 0.06). Plasma levels of beta-thromboglobulin and platelet factor 4 were lowest with patients supine and resting at 7 and 8 A.M., and increased with activity, with peak levels achieved at 3 P.M. (p less than 0.01). Thrombin-antithrombin III complexes (p = 0.44), D-Dimer (p = 0.36) and in vitro platelet aggregability to adenosine diphosphate (p = 0.20) did not show diurnal variation. There was a trend toward circadian variation in vitro platelet aggregability to epinephrine, but these changes did not achieve statistical significance (p = 0.16). Circadian changes of in vivo release of beta-thromboglobulin and platelet factor 4 correlated to patient activity and not to the morning peaks in ischemic events. These data indicate that changes in platelet function and not in coagulation have a diurnal occurrence.

Adenosine Diphosphate↗
PubMed1992

Markers for endothelial injury, clotting and platelet activation in preeclampsia.

The etiology of disseminated intravascular coagulation (DIC) in preeclampsia is not well understood. We measured plasma levels of fibronectin (FN), which may reflect endothelial cell injury, fibrinopeptide A (FPA), a specific marker of clotting, platelet counts (PLC) and mean platelet volumes (MPV), as well as beta-thromboglobulin (beta TG) and platelet factor 4 (Pf4), products of irreversible platelet activation in 24 preeclamptic patients and 24 controls matched for age, gestational age, labor status, and parity. In preeclampsia, FN and FPA were significantly elevated while PLC were significantly decreased (P less than 0.0001, less than 0.05 and less than 0.01, respectively). beta TG, Pf4, and MPV values did not show significant differences. These findings support the hypothesis that endothelial injury, clotting activation and platelet consumption are increased in preeclampsia. However, the much closer association of preeclampsia with FN levels as compared to FPA, beta TG, Pf4, suggests that endothelial injury is a more basic mechanism of preeclampsia than clotting or platelet activation.

Adolescent↗
PubMed1992

Pathogenesis of venous thrombosis.

This brief review attempts to describe the present understanding of the pathogenesis of venous thrombosis in general with special reference to venous thromboembolism in spinal cord injury patients with paralysis. The component parts of Virchow's triad are examined. Most venous thrombi seem to originate in regions of slow blood flow, ie, the large venous sinuses of the calf and thigh or in valve cusp pockets. Decreased blood flow or even stasis due to lack of the pumping action of the large muscle packages in paralyzed patients is undoubtedly one of the major factors. As blood pools, activation products of the coagulation system accumulate locally leading potentially to local hypercoagulability. Activation products of clotting and fibrinolysis can induce endothelial damage which in turn leads to further activation of the hemostasis system. Endothelial damage may also result from distension of the vessel walls by the pooling blood. Blood flow is further decreased by hyperviscosity due to elevated fibrinogen levels and dehydration. Some spinal cord injury patients may sustain direct trauma to the legs; others may encounter vessel wall damage by the immobilized limbs. Shortly after injury, certain changes develop in the clotting system, especially increases in components of the von Willebrand factor macromolecular complex and increased platelet aggregability which could further contribute to hypercoagulability. Recently, an inhibition of the fibrinolytic system was suggested which also could add to a prothrombotic state. All of these interrelated processes clearly explain the high risk of venous thromboembolism in spinal cord injury patients with paralysis which has been clearly demonstrated by many investigators. It is hoped that intense thrombosis prophylaxis will reduce the incidence of this potentially devastating complication.

Blood Coagulation↗
PubMed1992

Coagulation abnormalities in liver disease.

Hemostasis is intimately related to liver function, because most coagulation factors are synthesized by liver parenchymal cells and the liver's reticuloendothelial system serves an important role in the clearance of activation products. The extent of coagulation abnormalities depends upon the degree of disturbed liver function. Acute or chronic hepatocellular diseases may display decreases in the vitamin K-dependent factors (prothrombin; factors VII, IX, and X; proteins C and S), whereas other parameters remain normal. Patients with hepatic failure may present with the entire spectrum of factor deficiencies and may even develop disseminated intravascular coagulation (DIC). Patients with liver cirrhosis have a wide spectrum of abnormalities. Except for factor VIII:C and von Willebrand factor, all procoagulant and inhibitory factors are decreased, which is a reflection of impaired protein synthesis. Abnormal fibrinogen and prothrombin molecules can be identified. Platelets are quantitatively and qualitatively altered, and most patients develop DIC. Vitamin K deficiency leads to the production of abnormal vitamin K-dependent factors. The factors lack gamma-carboxy glutamic acid residues in the NH2-terminal part of their molecules. Surgery associated with the liver leads to major hemostasis alterations. The LeVeen shunt is invariably related to DIC. Bleeding with partial liver resection is mostly mechanically induced, but chronic DIC may be present. Orthotoptic liver transplantation is associated with severe hemorrhages. These are partly due to the pre-existing hemostasis defects and partly due to DIC with a marked fibrinolytic response. This is especially noted during the anhepatic phase and when the donor liver is perfused by the recipient's blood. Postoperative recovery is quick, provided the graft is not rejected. Postoperatively, there may be an initial hypercoagulable state, which could be related to the thrombosis occasionally encountered.

Blood Coagulation Disorders↗
PubMed1991

Hemostasis activation during esophageal variceal sclerotherapy with thrombin in cirrhotics.

Sclerotherapy of bleeding esophageal varices in liver cirrhotics is a common procedure, but little is known about the possible entry of sclerosants into the systemic circulation. We injected a mixture of thrombin, sodium tetradecyl, and cefazolin and studied the effect of this sclerosant on selected hemostasis parameters. Twenty-four patients with liver cirrhosis (Child's Classification C) were studied 29 times. Blood samples were drawn before and immediately after the injection of the sclerosant. In seven patients we collected a sample 30 minutes and 24 hours after treatment. Before injection, almost all patients had elevated D-dimer, t-PA and PAI-1 levels. Fibrinogen, antithrombin, alpha-2 antiplasmin, and protein C were decreased. Only thrombin/antithrombin III complex (TAT) levels were within normal ranges. Immediately after the injection, TAT, D-dimer, and t-PA levels rose significantly (P less than 0.001, P less than 0.01, P less than 0.001), PAI-1 and PC levels decreased (P less than 0.01), while antithrombin, alpha-2 antiplasmin, and fibrinogen concentrations were unchanged. TAT and D-dimer levels were still elevated after 24 hours (P less than 0.05). These data indicate that thrombin entered the systemic circulation (elevated TAT) and that the hemostasis system was briefly systemically activated (elevated D-dimer). In spite of these changes in the hemostasis system, clinically there were no detectable thrombotic or hemorrhagic complications.

Adult↗
PubMed1990

Changes in hemostasis activity during delivery and the immediate postpartum period.

Postpartum deep vein thrombosis is believed to be related to increased activation of the hemostasis system at the time of delivery. To date, studies designed to test this hypothesis have had relatively small sample sizes or used the measurement of specific coagulation factors and functional tests reflecting hemostasis activity in vitro. With the use of recent technologic advances we determined the effect of delivery on hemostasis in vivo by measuring 11 hemostatic indices simultaneously in 70 healthy pregnant women. Significant increases were found in fibrinopeptide A (p less than 0.001), beta-thromboglobulin (p less than 0.001), and platelet factor 4 (p less than 0.001), suggesting maximum platelet activation and fibrin formation at the time of delivery. In addition to continued clotting activity at 3 hours post partum, increased D-dimer, fibrin-fibrinogen degradation products, and decreased alpha 2-antiplasmin levels suggest maximum fibrinolysis. These changes reflect a peak in hemostatic activity at delivery and in the immediate postpartum period that may predispose the development of deep vein thrombosis.

Adult↗
PubMed1990

Why low molecular weight heparin?

The introduction of LMW heparins has opened new avenues for the management of patients with thromboembolic diseases. In contrast to regular heparin, the mean molecular weights are smaller and represent about half that of regular heparin. Yet, they are still somewhat heterogeneous and seem to differ from preparation to preparation in some of their biologic properties. No two LMW heparins are alike. In spite of these differences, certain commonalities do exist, which may represent an advantage of unfractionated heparin, especially in their use as a prophylactic antithrombotic modality: 1. They are at least as effective, if not more effective, as antithrombotic agents when compared with unfractionated heparin. 2. Their rate of absorption from the subcutaneous depots is more complete, leading to a longer efficacy in vivo. This translates to a once a day injection instead of the twice a day use of unfractionated heparin. 3. There are suggestions that their use is associated with less bleeding than unfractionated heparin, although the final outcome awaits completion of many ongoing clinical trials. LMW heparins are not free of bleeding complications, but hemorrhages seem to occur that are dose dependent. 4. The overall incidence of heparin-induced thrombocytopenia seems to be markedly reduced with LMW heparins. It is still encountered in an occasional patient and may be related to the preparation used. There is reason to believe that heparin fractions free of heparin-induced thrombocytopenia will be forthcoming. As LMW heparins are used therapeutically, new dosage schemes and new laboratory tests will have to be developed to assure maximum safety for the patients.

Dose-Response Relationship, Drug↗
PubMed1989

Prothrombin times and clottable fibrinogen determination on an automated coagulation laboratory (ACL-810).

Our laboratory evaluated an Automated Coagulation Laboratory (ACL-810) by Instrumentation Laboratory. Prothrombin times and fibrinogen levels from the ACL-810 were compared to results from a Fibrometer and another automated coagulation instrument - either the Coag-A-Mate (prothrombin times) or the Multistat III centrifugal analyzer (fibrinogen). The performance of different thromboplastins on the ACL-810 was also evaluated. Correlation studies revealed excellent performance characteristics and precisions for both the prothrombin time and fibrinogen not only with different instruments, but also with different thromboplastins on the ACL-810. Overall, we found the instrument to be quick, efficient, and easy to operate.

Autoanalysis↗
PubMed1989

Sepsis and antithrombin III, prekallikrein, and fibronectin levels in surgical patients.

Antithrombin (AT), prekallikrein (PK), and fibronectin (FN) were measured in the plasma of 400 patients with a variety of disease states seen at Detroit Receiving Hospital from October 1983 through June 1987. The average lowest AT measured in these 400 patients was 69 +/- 19 per cent (SD) (Normal = 75-120%). The average lowest AT level in 152 septic patients (50 +/- 17%) was significantly lower than in the 248 patients without sepsis (79 +/- 22%) (P less than 0.001). The average lowest PK levels measured in 132 patients was 52 +/- 19 (Normal = 80-120%). The average PK level in 64 septic patients (34 +/- 17%) was significantly lower than in 68 who were not septic (69 +/- 21%) (P less than 0.001). The average lowest FN levels measured in 109 patients was 230 +/- 118 mcg/ml (Normal = 200-350 mcg/ml). The average FN level in 47 septic patients (162 +/- 88 mcg/ml) was significantly lower than in the 62 nonseptic patients (285 +/- 138) mcg/ml. AT or PK levels less than 50 per cent or FN levels less than 150 mcg/ml during the first 24 to 48 hours after severe trauma or burns were associated with a development of later sepsis in 90 per cent, 77 per cent, and 70 per cent, respectively. Thus, low or falling levels of AT, PK, and FN may be of great help in predicting sepsis or providing an early diagnosis in critically ill or injured patients.

Antithrombin III↗