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D A Triplett

Publications and source records attributed to D A Triplett.

At least 91 records · Page 5Linked to original sources
PubMed1988

Lupus anticoagulants: misnomer, paradox, riddle, epiphenomenon.

Lupus anticoagulants (LA) were originally described in patients with systemic lupus erythematosus (SLE) and clinical bleeding. Following the original description, they were associated with numerous clinical conditions and it was soon appreciated that there was not an increased risk of hemorrhage. Hence the name is a misnomer which has resisted attempts at modification. The paradox of LA is the apparent increased risk of both arterial and venous thromboembolic events. Thus, a laboratory finding which was once associated with bleeding and subsequently was regarded as a nuisance has now acquired new respectability as a marker of a thrombotic predisposition. The riddle of the anticoagulant effect in vivo and the apparent procoagulant effect in vivo remains unsolved. Perhaps it is an epiphenomenon, but more importantly, it may open the door to greater understanding of the delicate regulatory systems which prevent thrombosis. LA exist in virtually every patient population. Therefore, they are no longer a topic of interest limited to hematologists, rather they have achieved multidisciplinary attention. Laboratories are now being asked to prospectively evaluate patients for the presence of LA or antiphospholipid antibodies (APA). The evaluation of LA, both in the research laboratory and clinic, should continue to provide important insights applicable to a variety of specialties.

Autoantibodies↗
PubMed1987

The sensitivity of different coagulation reagents to the presence of lupus anticoagulants.

The sensitivity and responsiveness of seven activated partial thromboplastin time reagents to the presence of lupus anticoagulants (LAs) was evaluated with a panel of 50 well-characterized LA plasmas. The results document that some reagents are clearly less responsive and sensitive to LAs; however, there is considerable variability between individual LA samples in these features. In addition, with 16% of these samples, immediate mixing studies showed correction of the activated partial thromboplastin time to the normal range with a 1:1 mixture of normal and LA plasma and 8% to 10% showed either a normal platelet neutralization procedure or a normal tissue thromboplastin inhibition procedure. Together, these findings provide further evidence of the laboratory heterogeneity of these inhibitors. The effect of this variability on the diagnosis of these inhibitors is discussed.

Blood Coagulation Disorders↗
PubMed1987

Clinical application of a functional assay for protein C.

Protein C (PC) is a vitamin K-dependent protein which functions as a physiologic anticoagulant. In the presence of another vitamin K-dependent protein, protein S, the activated form of protein C (APC) will degrade the active cofactors Va and VIIIa. Both hereditary and acquired deficiencies of PC have been associated with a predisposition to thromboembolic events. We have evaluated a commercial assay system (Stac lot Protein C) which utilizes an extract of snake venom (Protac) that directly activates protein C in vitro. Utilizing this assay, normal individuals, patients with hereditary protein C deficiency, patients who were stably anticoagulated with oral anticoagulants, and patients with lupus anticoagulants were evaluated. Significant discrepancies were noted between protein C antigen and protein C functional activity in patients receiving oral anticoagulants. In addition, patients with lupus anticoagulants may have falsely elevated values for functional protein C activity.

Administration, Oral↗
PubMed1987

The effects of heparin on the activated partial thromboplastin time of the College of American Pathologists Survey specimens. Responsiveness, precision, and sample effects.

Heparinized survey samples from the College of American Pathologists from 1981 through 1984 were reviewed to assess effects of the various reagents and instrumentation on the performance of the activated partial thromboplastin time (aPTT) in response to heparin. Responsiveness of the aPTT to the concentration of heparin as well as its sensitivity to the detection of heparin in the therapeutic range was most affected by choice of reagents. Precision was most affected by choice of instruments with photo-optical devices being roughly comparable. A previously described effect of calcium vs sodium salts of heparin was not supported by these data. Survey results were compared with results from fresh plasma samples from patients who had received heparin therapeutically and with response curves obtained from specimens heparinized ex vivo. The pattern of reagent dose responsiveness to the heparinized patient samples differed from that seen with survey samples and with the ex vivo heparinized fresh plasma samples. In addition, intrinsic characteristics of the individual specimens exerted substantial effects on the test results for all specimen types. Therefore, one cannot automatically assume that phenomena that hold for one form of plasma preparation are applicable to another. The nature and source of the heparinized plasma specimen must be taken into account when interpreting aPTT results.

Blood Coagulation Tests↗
PubMed1986

Characterization and comparison of immune-depleted and hereditary factor-VII-deficient plasmas as substrate plasmas for factor VII assays.

The functional activity of coagulation factors usually is determined using bioassays dependent on substrate plasmas deficient in the factor being measured. These are obtained most often from patients with hereditary deficiency and are frequently poorly characterized. The authors characterized seven commercially available hereditary Factor-VII-deficient substrate plasmas in terms of Factor VII activity and antigen level, and then compared them with a Factor-VII-deficient plasma prepared by immunoadsorption. All of the hereditary Factor-VII-deficient plasmas contained significant quantities of Factor VII antigen (120-217 ng/mL; normal, 250-600 ng/mL). One of the commercial substrate plasmas showed significant factor VII coagulant activity with a human thromboplastin. The sensitivity of the Factor VII assay system was dependent on both the source of Factor-VII-deficient plasma and the origin of the thromboplastins; human thromboplastin was more sensitive than rabbit thromboplastin, and immune-depleted plasma gave the most sensitive assay with each thromboplastin. These results indicate that immunoadsorbed plasma may be a superior reagent for coagulation factor assays.

Blood Coagulation Tests↗
PubMed1985

Use of the agarose gel method to identify and quantitate factor VIII:C inhibitors.

The agarose gel method for the detection and quantitation of Factor VIII inhibitors was investigated and compared with the Bethesda method. The agarose gel method was standardized for this study by modifications of the original method of Bird. (Bird P: Coagulation in an agarose gel and its application to the detection and measurement of factor VIII antibodies. Br J Haematol 1975; 29:329-340) Precision studies on values obtained by the agarose gel method indicated it is a reproducible assay. Random error was evident in both methods, but variance appeared to be greater in the Bethesda method for most of the samples evaluated. Comparison of the two methods with split patient samples indicated that proportional error is present in the agarose gel method, and that standardization of the method requires additional study. The agarose gel assay detected low levels of inhibitor (down to 3.4 Bethesda units) and all positive samples were identified. A screening procedure modification of the agarose gel method provided the sensitivity to detect Factor VIII inhibitor levels of less than 1.0 Bethesda units. The results indicated that the agarose gel method is a feasible alternative to the Bethesda method for both quantitative and qualitative determination of Factor VIII inhibitors. Furthermore, since reproducibility is better, it may be useful in detecting the "true" fluctuations of inhibitor titers in a given patient.

Blood Coagulation↗
PubMed1985

Oral anticoagulants.

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Administration, Oral↗
PubMed1985

The laboratory heterogeneity of lupus anticoagulants.

Approximately 2% of the patients screened in our laboratories with activated partial thromboplastin times are found to have a lupus anticoagulant. Recognition of lupus anticoagulants has assumed new importance because of a number of associated clinical conditions. Recurrent spontaneous abortions, arterial and venous thrombotic disease, and polyneuropathy have been described in patients with lupus anticoagulants. Although the clinical heterogeneity of these patients has been recognized increasingly, the laboratory identification of the lupus anticoagulant is still confusing and frustrating. In many cases, the diagnosis of this inhibitor is one of exclusion following a series of ambiguous mixing studies and variable factor assays. We studied ten patients with atypical laboratory results. Of particular significance are patients with a time-dependent enhancement of the lupus anticoagulant effect and patients with lupus anticoagulants that manifest a preferential inhibition of the prothrombin time rather than the activated partial thromboplastin time. We also confirmed the sensitivity of the platelet neutralization procedure in the identification of the lupus anticoagulant.

Adult↗
PubMed1985

Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis.

Twenty-six patients with hereditary factor VII deficiency (VII:C less than 10%) were evaluated using a panel of three thromboplastins of varying species and tissue origin in both coagulant and chromogenic assay systems. Normal values for the coagulation and chromogenic assays were 104% +/- 7% and 108% +/- 21%, respectively. Factor VII antigen was measured by a specific radioimmunoassay (normal, 470 +/- 112 ng/mL). The patients were divided into two groups based on the factor VII:Ag assay results. Group 1, 18 patients, had decreased levels of factor VII:Ag and group 2, eight patients, had normal levels of factor VII:Ag. The two groups were further subdivided on the basis of discrepant factor VII:C levels in the chromogenic and coagulant assays. The number of observed patterns of functional factor VII:C activity suggests a high degree of complexity of factor VII and thromboplastin interaction. Whereas no clinical bleeding was reported in any of the nine black patients evaluated, all Caucasians (16) and one Hispanic presented with mild to severe bleeding. Patients with factor VII:C greater than 10% using a human thromboplastin had a negative bleeding history, regardless of the activity measured with other thromboplastins. Factor VII activity measured with a human thromboplastin appears to correlate best with the clinical picture.

Adolescent↗
PubMed1984

Treatment modalities for inherited factor IX deficiency and the implications of inherited bleeding disorders.

Two cases of factor IX deficiency are presented. Therapeutic methods for anticipated abnormal bleeding during dental surgical procedures on these patients are discussed, and two are illustrated. One treatment regimen, plasmapheresis, has not been discussed previously in the dental literature. Epidemiologic data relative to the frequency and type of inherited bleeding diatheses seen by the dental surgeon were obtained from a 2-year retrospective study involving all admissions to the dental service of a regional hospital. These data, in conjunction with the presented cases, illustrate the need for dentists, especially those in the surgical specialties, to be familiar with the inherited bleeding diatheses and their treatment.

Adult↗
PubMed1984

Proficiency testing and standardization of prothrombin time: effect of thromboplastin, instrumentation, and plasma.

Prothrombin times accumulated from ten different proficiency testing surveys were analyzed in terms of a linear additive model described by Evatt et al (Clin Lab Haemat 1981; 3:331-342). Different types of lyophilized plasma samples were used, i.e., plasmas artificially depleted of coagulation factors by adsorption to aluminum hydroxide, and pooled plasmas of patients receiving coumarin drugs. For each plasma sample, both instruments and thromboplastins had a highly significant effect on the prothrombin time. For most instruments and thromboplastins, a good correlation was found between instrument effect or thromboplastin effect and the mean prothrombin time if various artificially depleted plasma samples from a single manufacturer were used. Artificially depleted plasmas from a second manufacturer gave different relationships between estimated effects and mean prothrombin time. Relationships based on lyophilized pooled patient plasmas were different from those of artificially depleted plasmas from either manufacturer. The potential use of the additive linear model for standardization of the prothrombin time in monitoring oral anticoagulant therapy is discussed. Additional studies are required to establish the suitability of this model to define a universal scale for prothrombin times of fresh plasma samples of anticoagulated patients. If suitable, the model can be linked to the International Normalized Ratio proposed by the World Health Organization.

Analysis of Variance↗
PubMed1984

The extrinsic system.

Factor VII appears to be the key regulatory protein in the initiation of both the intrinsic and extrinsic systems of coagulation. The single chain, or zymogen form, of factor VII possesses enzymatic activity which makes it an ideal candidate for the initiation of coagulation following vascular injury. A number of interactions between the intrinsic and extrinsic systems of coagulation have been identified. It appears that factor VII is capable of directly activating factor IX and vice versa. The study of factor VII variants with associated thromboembolic complications may provide a number of answers regarding the initiation and regulation of the blood coagulation process.

Blood Coagulation↗
PubMed1984

The use of synthetic substrates in the coagulation laboratory.

The development and adaptation of synthetic substrates has introduced new concepts and methodologies to the coagulation laboratory. Synthetic substrates offer potentially improved standardization over conventional testing, providing a rapid, sensitive, and specific way to measure enzymes directly.

Blood Coagulation Factors↗
PubMed1983

A clinical study on the use of a fluorogenic substrate assay of plasminogen.

A fluorogenic substrate assay of plasminogen was compared with acceptable methodologies, i.e., caseinolytic and radial immunodiffusion assays. Reference intervals based on a population of 25 members of the laboratory staff were 2.5-3.8 CTA u/ml (fluorogenic), 2.2-4.0 CTA u/ml (caseinolytic) and 8.7-14.3 mg/dl (RID). Ninety eight determinations were performed on 65 patients. Regression analysis showed linear correlation between the fluorometric and caseinolytic assays (r = 0.8046, p less than 0.03) and between the fluorometric and immunologic assays (r = 0.8572, p less than 0.005). Pre-operative and post-operative determinations were performed on 33 patients undergoing coronary artery bypass surgery and there was a consistent and significant (10%-76%) decrease in the plasminogen levels post-operatively (p less than 0.01). Twenty-five patients with various malignancies were compared with the normal population; no significant difference in the plasminogen levels was observed between the two groups.

Caseins↗
PubMed1983

Fluorogenic substrate assay of antithrombin III: a clinical study.

The fluorogenic substrate assay of antithrombin III (AT III) was compared with a thrombin inhibition (two-stage) clotting test and a radial immunodiffusion assay. Normal ranges based on a population of 25 individuals were 88-121% (fluorogenic substrate), 72-111% (clotting) and 22.5-35.3 mg/dl (RID). A clinical comparison of the methods showed a linear relationship between the fluorogenic substrate and immunologic methods (r = 0.69, p less than 0.005), as well as between the fluorogenic substrate and clotting methods (r = 0.75, p less than 0.005). The fluorogenic substrate assay reflected the highest incidence of low AT III levels in all three clinical groups included (36 patients with arteriosclerosis, 18 with fractures and 37 with thrombosis/embolism).

Antithrombin III↗
PubMed1983

DDAVP: review of indications for its use in the treatment of factor VIII deficiency and report of a case.

Classic hemophilia or factor VIII deficiency is a recessive, sex-linked bleeding diathesis. The primary clinical problem is hemorrhage, which can be severe and often life threatening, even in the presence of only minor trauma. In the past this inadequate hemostasis has been treated with transfusions of cryoprecipitate, fresh frozen plasma, or commercially prepared factor VIII concentrate. Unfortunately, such treatment carries with it a number of risks, including the development of hepatitis B or hemolytic anemia and the formation of anti-factor VIII antibodies. Because of hemorrhage severity and the risks of conventional treatment, elective surgery in general and oral surgery in particular have often been neglected in patients with hemophilia. This article reviews a drug, 1-desamino-8-d-arginine (DDAVP), heretofore not discussed in the dental literature, and reports on its use in conjunction with epsilon-aminocaproic acid (EACA), a synthetic antifibrinolytic agent, in the surgical dental treatment of a patient with hemophilia A. The results suggest that certain dental surgical procedures can be performed in the presence of subclinical and mild hemophilia without conventional factor VIII replacement therapy with its associated costs and risks.

Adult↗