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J M Walenga

Publications and source records attributed to J M Walenga.

189 records · Page 11Linked to original sources
PubMed1983

Newer avenues in the monitoring of antithrombotic therapy: the role of automation.

In the future, we may find that antithrombotic therapy provides its major effects other than by Factors Xa and IIa inhibition, in which case a panel of assays may be of clinical use to determine how a given patient is responding to therapy. All methods discussed previously for direct factor assays, global tests, or specific factor inhibition can be modified for synthetic substrates. With instruments such as the IL Multistat III centrifugal analyzer, which has detection capabilities for visible light, fluorescence and light scatter, it will be possible to panel profile synthetic substrate-based assays, immunologic assays (for example, platelet release products or circulating complexes of enzyme-inhibitor, such as thrombin-AT III) and possibly platelet aggregations/luminescence in one rotor. The field of coagulation is rapidly expanding in the development of newer tests to measure newly discovered proteins (protein C), development of new drugs and therapeutic regimens, and incorporating immunologic and enzymologic technologies and clinical chemistry standardization and quality control practices. Throughout this period of growth, automation has been in the forefront and is playing an ever-increasing role in every old and new aspect of coagulation evaluation. We are aware of the advantages that accompany any automated device over manual techniques, so there should be much hope and expectation for the new hemostasis and thrombosis laboratory.

Administration, Oral↗
PubMed1983

Diagnostic efficacy of newer synthetic-substrates methods for assessing coagulation variables: a critical overview.

With the introduction of synthetic substrates, many newer methods have been developed for testing coagulation parameters. Some of these methods are used in clinical settings, and many have been evaluated for their diagnostic efficacy in various coagulation disorders. Clinical chemistry laboratory instrumentation has been used to accommodate these methods. Commercially available kits for antithrombin III, heparin, plasminogen, alpha 2-antiplasmin, and factor X are used by many laboratories. Individual reagents have also become available and are being used to develop assays for routine diagnostic use. The development of suitable standards is rapidly underway, and their availability will facilitate adoption of these methods by hospital laboratories. Many of the synthetic-substrate-based assays that have been introduced for routine diagnostic purposes have been published recently. Here, we provide an overview of the newer amidolytic methods for the measurement of certain coagulation variables.

Anticoagulants↗
PubMedDate not supplied

Postburn edema and related changes in interleukin-2, leukocytes, platelet activation, endothelin-1, and C1 esterase inhibitor.

Interleukin-2 (IL-2) promotes multisystem organ edema, lung neutrophil sequestration, and platelet activation through alterations in the microvascular barriers and permeability. IL-2, complement, platelet, and vascular endothelial activation were evaluated in 60 patients. One-factor analysis of variance indicated a significantly increased absolute neutrophil count on day 1 (p < 0.0001) and decreased C1Inh, p = 0.0001, with elevated IL-2 levels in the 20% to 40% group (p = 0.008). Endothelin-1 levels were significantly increased in the 20% to 40% total body surface area group on day 5. The absolute neutrophil count was significantly reduced in both groups, and C1Inh rose to near normal levels by day 5. No significant elevations of 6-keto prostaglandin F1 alpha were observed on day 1 or day 5 in the < 40% total body surface area group; however, these levels were significantly elevated on day 1 in the > 40% total body surface area group. Thromboxane B2 and platelet factor 4 were significantly elevated in all groups (p = 0.001) on days 1 and 5. Regression analysis implicated infection as a significant contributor to the IL-2 variations (r2 = 0.61), with inhalation injury minimally affecting IL-2 plasma levels (r2 = 0.09). Generalized edema increased with increasing burn wound size in parallel with elevated IL-2 and endothelin-1 levels, reduced C1Inh levels, and leukocytosis in the first week after thermal injury. These data suggest that there are dynamic interactions among the endothelium, cytokine stimulation, leukocytosis, complement, and platelet activation in promoting the microvascular permeability.

Adolescent↗
PubMedDate not supplied

Antithrombin(H) concentrate infusions are safe and effective in patients with thermal injuries.

An antithrombin (AT) deficiency develops in patients with thermal injuries as a result of the subclinical disseminated intravascular coagulation. We conducted a pilot study to assess AT(Human [H]) concentrate infusions for safety and efficacy in thermal injury. Nine patients with burns who received Thrombate (Bayer Corporation, Berkeley, Calif) AT(H) concentrate infusions every 8 hours to raise the plasma level to 175% in the first 72 hours after injury were compared with 9 control patients with burns. Admission AT plasma levels were 45%+/-10% in patients treated with AT(H) versus 49%+/-18% in control patients (normal, 100%+/-20%). Day-2 to day-4 levels were 120%+/-25% in patients treated with AT(H) patients versus 50%+/-12% in the control patients (P < .002). In the group treated with AT(H), the time to wound healing was shorter for all body regions and was significantly shorter for the hand (P < .02). Compared with control patients, patients treated with AT(H) had similar blood loss per grafted area. A trend toward fewer autografting procedures, a shorter meshed autograft healing time, and a decreased hospital stay was found for the patients treated with AT(H). AT(H) concentrate infusions are safe with thermal injury and are a viable option to shorten the length of hospitalization and to promote graft viability and survival. Clinical trials to confirm the benefit of this medication in the acute phase of thermal injury would be worthwhile.

Adolescent↗
PubMedDate not supplied

Successful use of recombinant hirudin and its monitoring by ecarin clotting time in patients with heparin-induced thrombocytopenia undergoing off-pump coronary artery revascularization.

Refludan (lepirudin-rDNA for injection) is the first direct thrombin inhibitor approved by the United States FDA for anticoagulation to patients with heparin-induced thrombocytopenia (HIT). It was monitored by ecarin clotting time (ECT) assay in patients with HIT. Case histories and clotting parameters for three patients undergoing off-pump coronary artery revascularization procedure are discussed. The first patient received r-hirudin at a dose of 0.2 mg/kg intravenous (IV) bolus followed by 0.15 mg/kg/hour infusion. The second patient received 0.4 mg/kg IV bolus followed by infusion of 0.15 mg/kg/hour infusion. The third patient with renal failure received 0.2 mg/kg IV bolus followed by an infusion of 0.02 mg/kg/hour. Blood samples were drawn at baseline, 5 minutes post bolus and every 15 minutes during the coronary artery revascularization procedure. ECT was performed immediately on the citrated whole blood samples using the ECT cards in conjunction with the point-of-care, the thrombolytic assessment system (TAS) Analyzer (Pharmanetics, Raleigh, NC). The plasma samples were then analyzed for APTT and liquid ECT assay performed on a kinetic centrifugal analyzer (ACL 300 Plus). The ECT by cards was ideally maintained above 600 seconds during the surgical procedure. Additional boluses of Refludan were given as and when necessary (ECT < 600 sec) in order to maintain adequate anticoagulation. The calculated circulating concentrations of Refludan, following a bolus administration, based on the ECT cards, liquid ECT and APTT were 3.20 +/- 1.3, 3.51 +/- 1.35 and 2.02 +/- 1.19 microg/mL, respectively.

Aged↗
PubMedDate not supplied

Low molecular weight heparins. An objective overview.

The introduction of low molecular weight heparins has added a new dimension to the management of thrombotic disorders. Ten LMWHs are currently available for clinical use. Although these agents have been primarily developed and used in European countries, other countries, including the US, have started to evaluate their usefulness. Well designed clinical trials have been carried out for different clinical indications with several of these products. In contrast to other prophylactic antithrombotic drugs (heparin, warfarin, aspirin), LMWHs have provided consistently impressive clinical results. Moreover, the other products have less desirable tolerability profiles than that of LMWHs. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of each LMWH is distinct in itself being characteristic to only that particular drug. Besides the currently available LMWH preparations, some 14 other agents are under development at this time. Although both the original and newer products have similar basic characteristics, the physicochemical properties and the pharmacological actions of each of these agents may differ significantly. All manufacturers should follow the Food and Drug Administration (FDA) guidelines and conduct their own clinical trials on each of their products. Many significant developments of LMWHs will take place in the coming years; in addition to development for prophylactic use, LMWHs will be developed for therapeutic intervention.

Heparin, Low-Molecular-Weight↗