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[Thromboplastin activity of extracts of human thyroid glands (author's transl)].

Aqueous extracts of thyroid glands were prepared from 25 surgical specimens of 19 patients. The average prothrombin time of sixteen 3:4 diluted extracts of thyroids from 13 euthyroid patients was 16.8 +/- 2.3 sec as measured with 100% human plasma. Under similar conditions the average prothrombin time of extracts obtained from the grey matter of three human brains was 18.4 +/- 0.3 sec. The thyroid may thus be considered as an organ containing one of the highest concentrations of tissue thromboplastin.

Humans↗

Activated coagulation and activated partial thromboplastin times in assessment and reversal of heparin-induced anticoagulation for cardiopulmonary bypass.

In 22 adult patients, activated coagulation times (ACT) were compared to activated partial thromboplastin times (aPTT) before, during, and after cardiopulmonary (CP) bypass surgery. After intravenous heparin (150 units/kg), mean ACT increased from 131 +/- 14 (mean +/- SD) to 362 +/- 72 s (P less than 0.001). With 1.5 units of heparin/ml added to the priming solution of the pump, ACT ranged from 230 to 541 s and aPTT was always 300 s or longer. Activated PTT appears to be less sensitive to changing plasma heparin levels than ACT. Heparin neutralization with a protamine/heparin ratio of 1.0 returned ACT and aPTT to preheparin levels. No abnormal bleeding tendency was seen during the recovery period, and ACT and aPTT remained at preheparin levels. In 10 infants and children undergoing open-heart surgery, ACT was measured in response to the same heparin and protamine regimen. Baseline (113 +/- 14 s) and post-heparin (297 +/- 90 s) ACT were shorter in children than in adults (P less than 0.01). After protamine, ACT was still longer than baseline (134 v 113 s, P less than 0.05). Infants and children seem to require more heparin/kg body weight than adults to achieve comparable ACT levels.

Aged↗

Reappraisal of thromboplastin.

Proficiency testing surveys in the state of New York indicate that despite increased sophistication in instrumentation, there has been no real improvement in interlaboratory reproducibility in prothrombin-time determinations over the last 10 years. This lack of improvement most pronounced in the therapeutic range of 20 to 30 sec. One reason may be that between types produced by the same manufacturer. While it has been possible in several laboratories to synthesize experimentally a thromboplastin with known content of lipid and active protein, no efforts have been made to make such a product by the same manufactures. While it has been made to make such a product commercially available. Blood levels of of warfarin were measured but cannot be reliably used to monitor anticoagulation. In a preliminary study, factor Xa activity was measured using chromogenic substrate S2222. Factor Xa activity gave a positive correlation with prothrombin times of patients receiving warfarin therapy. Chromogenic substrate factor assays may represent a future method of choice for controlling anticoagulant therapy.

Animals↗

Comparison of reagents for determining the activated partial thromboplastin time.

Six commercially available reagents for the determination of the activated partial thromboplastin time have been evaluated and compared with respect to their sensitivity to the coagulation factors VIII, IX and XI and to their response to heparin. Some variation was observed among the reagents regarding their sensitivity to factor XI and even greater differences were obtained with factors VIII and IX. It was also clear that none of the reagents was sensitive to the same extent to the factors tested. The sensitivity to heparin shows considerable variation, in terms of time as well as mode of response to increasing heparin levels. In four reagents this response is linear, it is logarithmic in one and the remaining one is yet again different. It seems unlikely that any standardization of the APTT determination is at present possible with the reagents studied.

Factor XI Deficiency↗

The effects of inaccurate blood sample volume on prothrombin time (PT) and activated partial thromboplastin time (aPTT).

The results of determinations of the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are frequently used to assess hemostatic function. Accurate results for these laboratory tests depend on many variables, one of which is the ratio of plasma to anticoagulant. We studied 12 patients and 4 normal subjects to determine the effects of sample volume on PT and aPTT. We conclude that underfilling may produce profound effects, particularly on the aPTT. In contrast, overfilling rarely affects the results. The greatest effects of sample volume were observed in specimens in which the true PT or aPTT was elevated. A normal PT or aPTT result on any specimen, regardless of sample volume, strongly suggests that the true value is normal.

Adult↗

Synthesis of thromboplastin protein by a murine macrophage-like cell line.

The established murine macrophage cell line J-774.1 responds to endotoxin with synthesis of thromboplastin apoprotein. The response develops in the absence of added lymphocytes and there is no increased responsiveness in cocultures of J-774.1 cells and BALB/c lymphocytes. J-774.1 cells therefore do not depend on lymphocyte cooperation for their response to endotoxin.

Animals↗

Definition of the population at risk of bleeding due to factor XI deficiency in Ashkenazic Jews and the value of activated partial thromboplastin time in its detection.

The previously found high gene frequency of hereditary Factor XI deficiency among Ashkenazic Jews, and the risk of bleeding following trauma in this disorder, prompted us to define the population at risk of bleeding and to evaluate the activated partial thromboplastin time (APTT) as a screening test for its detection. The APTT values of 30 patients with severe Factor XI deficiency (0 to 0.14 unit/ml) overlapped only minimally with the APTT of 56 healthy subjects with Factor XI levels greater than 0.5 unit/ml. In contrast, APTT values of partially deficient patients (Factor XI: 0.15 to 0.49 unit/ml) overlapped substantially with the APTT values of the healthy subjects. However, when only subjects at risk of bleeding were considered (Factor XI less than 0.3 unit/ml), the overlap of APTT values was much smaller. The apparent frequency of this population at risk in the general Ashkenazic population was found to be 3.05%. If a cutoff point of an APTT value at the 80th percentile of the normal range is taken for detection of subjects belonging to this group, one will miss only 4.4% of these cases, with confidence limits of 0.1 to 21%.

Blood Coagulation Tests↗

Spectrophotometry of tissue thromboplastin in cerebrospinal fluid.

We describe a two-stage method for measuring thromboplastin in cerebrospinal fluid, based on the amidolytic determination of the generation rate of Factor Xa. We investigated the effect of variations in the duration of incubation, and in pH, temperature, and concentrations of calcium, buffer, and prothrombin complex (source of Factors VII and X). Optimal assay conditions are specified. The detection limit is 6 units/L and the results indicate an upper limit of normal of 14 units/L. The coefficients of variation were 7.7% within-day and 9.2--16.0% day-to-day, depending on the concentration.

Factor X↗

[Distribution of heparin and its complex compounds in the tissues of animals maintained on an atherogenic diet following intravenous administration of a thromboplastin-heparin complex].

After intravenous infusion of the thromboplastin-35- S-heparin complex into rats, maintained on the atherogenic diet within a prolonged period, distribution of the label in the animal tissues and its clearance were studied; total and non-enzymatic fibrinolytic activities were estimated. Inhibition of functions of the anticoagulation system, caused by long-term atherogenic diet in the animals, led to inhibition of the initial steps of heparin clearance as well as to alteration of the glycosaminoglycan distribution in various tissues. At the same time, formation and accumulation of heparin complexes as well as the non-enzymatic fibrinolytic activity were decreased in some tissues.

Animals↗

Alterations of prothrombin time and activated partial thromboplastin time in dogs with hepatic disease.

Reference intervals for prothrombin time (PT) and activated partial thromboplastin time (APPT) of undiluted and serial dilutions of citrated platelet-poor plasma were determined for 30 healthy dogs. The PT and APTT were similarly determined for 32 dogs with naturally occurring hepatic disease. Hepatic disease was confirmed by histopathologic examination of hepatic biopsy materials and comprised degeneration (13 dogs), inflammation (11 dogs), cirrhosis (4 dogs), and neoplasia (4 dogs). Coagulation test values were compared with serum alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase activities and Bromsulphalein retention for sensitivity in detecting hepatic disease in the dog. Coagulation test results were at variance with reference values in 66% of the 32 dogs with hepatic disease; serum alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase were increased in 59%, 72%, and 75%, respectively and Bromsulphalein retention was increased in 22% of the 32 dogs. Thus, the PT and APTT were sensitive indicators of hepatic disease. However, the PT and APTT lacked specificity for any given hepatic disease. The sensitivity of the coagulation tests for detecting hepatic disease was enhanced by using dilutions of citrated platelet-poor plasma. Only 15% of dogs with hepatic disease showed variances from reference values in the coagulation tests done with undiluted plasma, but 66% showed variances in the tests with dilutions of plasma. Coagulation tests were also done in 13 dogs with normal hepatic function amd morphology, but with various extrahepatic diseases: chronic renal disease (5 dogs), dirofilariasis (4 dogs), encephalitis (1 dog), cutaneous disease (2 dogs), and femoral fracture (1 dog). Twelve of the 13 dogs had coagulation test values within the reference intervals.

Animals↗

Lectin stimulation of tissue thromboplastin activity in human monocytes in vitro.

Lectins (phytohaemagglutinin, concanavalin A and wheat germ agglutinin) trigger an increase in tissue thromboplastin activity of human monocytes in vitro. The presence of serum was not necessary and did not enhance the activity. The increase was inhibited by cycloheximide and actinomycin D, suggesting that de novo protein synthesis is involved.

Agglutinins↗

Laboratory monitoring of heparin therapy--the effect of different salts of heparin on the activated partial thromboplastin time.

Data from the 1978 CAP Hematology Survey were analyzed for the effect of sodium and calcium salts of heparin on the activated partial thromboplastin time (APTT). The results indicate that the sodium salt of heparin prolongs the APTT more than the calcium salt at a heparin concentration of 0.2 units/ml. Furthermore, there was a variable response of the different APTT reagents to the different heparin salts. Data from the 1979 CAP Hematology Survey showed a greater sensitivity of the Automated APTT reagent and the Platelin Plus Activator of General Diagnostics compared with Actin (Dade) and Thrombofax (Ortho) at therapeutic heparin levels of 0.2 units/ml to 0.4 units/ml. The 1979 CAP heparin questionnaire results are presented and analyzed.

Blood Coagulation Tests↗

The effect of simultaneous intravenous administration of nitroglycerin and heparin on partial thromboplastin time.

The purpose of this study was to determine whether intravenous nitroglycerin, when infused simultaneously through the same tubing with heparin, alters the anticoagulant effect of heparin as evidenced by partial thromboplastin time (PTT) values. A time series, cross-over design was used. The study included patients admitted to the Coronary Care Unit with a diagnosis of unstable angina. Patients were randomly assigned to one of two treatment groups: (1) heparin/nitroglycerin infused in the same site or (2) heparin/nitroglycerin infused in separate sites. After 18 hours, treatments were reversed. PTT results were measured seven times per subject. Ninety-eight subjects, 70 males and 28 females, participated. Mean age was 62.4 +/- 9 years. Using repeated measures analysis of variance, there was no change in the patients' PTTs (p = 0.47). Prior to this study, research was divided on whether nitroglycerin interferes with heparin's activity. This study indicates no significant difference in PTT in subjects receiving these infusions via separate or the same intravenous sites.

Adult↗

[Thromboplastin. A short review of new findings].

Recent findings of thromboplastin (TRPL) investigations are presented in a brief survey. After enumerating the possibilities of separating this lipoprotein into two shares, the chemical characterization of protein and lipid fraction is represented, the possibilities and conditions of recombining both shares are mentioned and the effectiveness of TRPL in the exogenous coagulation system is illustrated. Furthermore, the liberation of TRPL by leukocytes is referred to and feasible mechanisms of this liberation are discussed. Finally the relations of TRPL to tumour cell materials promoting coagulation and from amnion liquid are discussed.

Amnion↗

Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy.

The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.

Factor VII↗

The effect of aprotinin on the response of the activated partial thromboplastin time (APTT) to heparin.

Aprotinin, a broad spectrum serine proteinase inhibitor, is becoming increasingly used to control bleeding during surgery. Heparinized patients treated with aprotinin for cardiac surgery have a much longer activated clotting time (ACT) than expected for the dose of heparin used and a similar effect has been observed with the activated partial thromboplastin time (APTT). Since APTT reagents vary in their sensitivity to heparin we compared the effect of aprotinin on 25 commercially available products with respect to the APTT response to heparin. Aprotinin (Bayer) was added to normal, pooled, citrated plasma at concentrations of 0, 100, 200, 300 and 400 kallikrein inhibition units (KIU)/ml and mucosal heparin was then added to give concentrations of 0, 0.25, 0.5, 0.75 and 1.0 IU/ml. Duplicate APTTs were performed on each of these 25 plasma samples according to the manufacturers' instructions. As expected, different commercial reagents exhibited different sensitivities to heparin. There was also variation in the sensitivity to aprotinin but this did not correlate with the heparin sensitivity. The prolongation of the APTT by heparin was markedly increased by aprotinin. For example, APTT ratios at 0.5 IU/ml heparin increased up to eight-fold in the presence of 'therapeutic' levels of aprotinin (200 KIU/ml) and this effect was even more pronounced at higher heparin levels. The activator used did not significantly influence the effect of aprotinin on the APTT although there was a trend for kaolin-activated reagents to be less affected by the addition of aprotinin to heparinised plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

Activated partial thromboplastin time for automated techniques: a comparison of two commonly used reagents.

In a comparison between two widely used activated partial thromboplastin time reagents (Instrumentation Laboratories, Manchester low-opacity), using one popular instrument (Automated Coagulation Laboratory, model 300R), a wide range of defects and 40 normals were tested. There was generally good agreement between methods, although for samples from patients on high heparin dosages the agreement was poor. The manufacturer's recommendation for the therapeutic range for heparin for the Instrumentation Laboratory reagent was lower than the range in current general use. The Manchester reagent was more sensitive to the lupus anticoagulant.

Heparin↗