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Effects of S-8527 (1, 1-bis (4'-(1"-carboxy-1"-methylpropoxy) phenyl) cyclohexane), a new hypolipidemic compound, on platelet aggregation, adhesiveness and blood coagulation in rats.

Effects of S-8527 (1,1-bis[4'-(1"-carboxy-1"-methylpropoxy) phenyl] cyclohexane) on platelet aggregation, adhesiveness and blood coagulation were examined in rats. In animals maintained on a semisynthetic diet containing sucrose (62%) as the only carbohydrate source, platelet adhesiveness increased as compared with that in rats fed a normal chow pellet. Under these experimental conditions, oral dose of S-8527 (30-300 mg/kg) for 14 days decreased platelet adhesiveness and ADP-induced platelet aggregation, but did not decrease collagen-induced platelet aggregation. S-8527 also showed a slight but significant increase of R value of thrombelastograph. In rats which were fed a normal chow pellet oral dose of S-8527 for 14 days did not significantly affect the several tests of platelet function and blood coagulation. These results suggest that S-8527 normalizes the platelet function in a hyper-adhesive state, but does not affect the platelet function in a normal state.

Adenosine Diphosphate↗

Studies on alterations in blood coagulative and fibrinolytic activities after single and multiple administrations of carbon tetrachloride in mice.

The time course of alterations in coagulative and fiblinolytic activities was studied in CCl4-induced liver disease in mice. Liver disease was induced by administration of 20% CCl4 in olive oil (p.o.). After single administration of CCl4, significant prolongation of r and k values and decrease in the ma value of thromboelastogram and apparent prolongation of PT and PTT were seen at 24 hr. Fibrinogen content decreased from 12 to 72 hr after single administration, while a mild but significant decrease in fibrinogen was observed after multiple administrations. The activity of factor XIII increased from 5 to 12 hr and then decreased from 24 to 168 hr after single administration. The activity of the hepaplastintest and Antithrombin III decreased apparently after single and multiple administrations. The plasminogen content and the activity of alpha 2-plasmin inhibitor decreased severely after single and multiple administrations. These results indicate that the coagulative and fibrinolytic activities were decreased to the most lowest value at 24 or 48 hr after single administration of CCl4, and the severe suppression of fibrinolysis and the mild decrease in coagulative activity were observed after multiple administrations of CCl4. The reason for the different effects between single and multiple administrations on coagulative and fibrinolytic systems was discussed.

Acute Disease↗

Blood coagulation studies in guineapigs (Cavia porcellus).

Blood coagulation studies were performed on 45 healthy, adult guinea pigs. Additionally thrombelastograms of 30 animals were recorded. Guineapigs revealed short partial thromboplastin times and euglobulin lysis times, but long prothrombin times and thrombin times. Fibrinogen values were within the range of human normal values. Biphasic ADP-induced aggregation of platelets, as occurs in man, was found in 29% of the animals. Short r (reaction time until the beginning of clot formation) and k times (time from the beginning of clot formation until an amplitude of 20 mm) of their thrombelastograms indicate, that whole blood clotting is enhanced in guineapigs. Higher maximum amplitudes in this species suggest a stronger clot stability than in man.

Adenosine Diphosphate↗

Effects of unfractionated heparin, low-molecular-weight heparin, and heparinoid on thromboelastographic assay of blood coagulation.

Thromboelastography (TEG) has been used increasingly as an intraoperative hemostasis monitoring device. Low-molecular-weight heparins are given increasingly to reduce the development of antibodies against the heparin-platelet factor 4 complex, and heparinoids are given to patients who have developed the antibody. We studied the effect of unfractionated heparin, a low-molecular-weight heparin (enoxaparin sodium [Lovenox]), and a heparinoid (danaparoid sodium [Orgaran]) on blood clotting assayed with TEG (TEG clotting) in vitro and the efficacy of protamine sulfate and heparinase for reversing the effect. Heparin, enoxaparin, and danaparoid all caused a dose-dependent inhibition of TEG clotting of normal blood. Concentrations of enoxaparin and danaparoid that totally inhibited TEG clotting only minimally prolonged the activated partial thromboplastin time. While inhibition of TEG clotting by heparin and enoxaparin was reversed by protamine sulfate and heparinase, inhibition by danaparoid was reversed only by heparinase. Abnormal TEG clotting was observed in patients receiving enoxaparin whose plasma level of the drug was more than 0.1 antiXa U/mL. However, the degree of TEG abnormality did not always coincide with plasma levels of the drug.

Antibodies↗

Thromboelastography detects inadequate response to abciximab therapy during stent-assisted cerebral aneurysm coil embolization complicated by stroke.

INTRODUCTION: Thromboembolic stroke is the most common severe complication following coil embolization of intracerebral aneurysms, with a 5% incidence of permanent deficits. Despite heparin anticoagulation, rescue therapy with the platelet glycoprotein IIb/IIIa receptor antagonist abciximab may be required. However, we describe a failure of abciximab rescue therapy and discuss the importance of monitoring the variable individual response to abciximab. CASE REPORTS: Two patients underwent stent-assisted cerebral aneurysm coil embolization complicated by thromboembolic stroke. In one patient, abciximab rescue therapy failed and was associated with a poor neurological outcome. Thromboelastography (TEG model 5000; Haemoscope, Skokie, IL) and platelet aggregometry suggested inadequate platelet inhibition, although other tests of platelet function suggested adequate inhibition. CONCLUSION: We describe a failure of regular-dose abciximab rescue therapy for thromboembolic stroke-complicating stent-assisted cerebral aneurysm coil embolization. The use of TEG to individualize abciximab dosing in this setting may improve patient outcome, as it tracks a pattern of coagulation consistent with the clinical picture.

Abciximab↗

Point-of-care testing in the cardiovascular operating theatre.

Point-of-care testing (POCT) remains under scrutiny by healthcare professionals because of its ill-tried, young history. POCT methods are being developed by a few major equipment companies based on rapid progress in informatics and nanotechnology. Issues as POCT quality control, comparability with standard laboratory procedures, standardisation, traceability and round robin testing are being left to hospitals. As a result, the clinical and operational benefits of POCT were first evident for patients on the operating table. For the management of cardiovascular surgery patients, POCT technology is an indispensable aid. Improvement of the technology has meant that clinical laboratory pathologists now recognise the need for POCT beyond their high-throughput areas.

Blood Gas Analysis↗

Coagulation and fibrinolysis in viable mid-trimester pregnancies of normal, intrauterine growth retardation, chromosomal anomalies and hydrops fetalis and their eventual obstetric outcome.

A total of 71 pregnant women diagnosed by ultrasound to have viable fetus in late mid- trimester pregnancies of normal, IUGR, hydrops fetalis and chromosomal anomalies were studied for their coagulation, fibrinolytic and inhibitor levels with association on eventual obstetrics outcome. A hypercoagulable state was observed in all the pregnancies studied. However, higher hypercoagulation evidenced by significantly raised prothrombin formation and clot elasticity together with higher levels of D-dimer, uPA antigen and PAI-1 than observed in normal pregnancy suggests a hyperfibrinolytic/inhibitor state in hydrops fetalis pregnancy associated with bad obstetric outcome. In IUGR pregnancy associated with good outcome further enhanced clot elasticity was seen whilst no significant differences were observed in pregnancy with chromosomal anomalies when compared to uncomplicated normal pregnancy. Our study suggests that in hydrops fetalis pregnancy, further enhanced prothrombin formation and hyperfibrinolysis/inhibitor at late mid-trimester is associated with a poor obstetric outcome.

Adult↗

New neonatal problems of blood coagulation and fibrinolysis. I. The change of plasmin inhibitor levels in the newborn infant.

"Hemorrhage in the newborn" has long been recognized as merely a result of vitamin K deficiency. However, it is also recognized that fibrinolysis, especially the correlation between the plasminogen-activator and plasmin-inhibitors, play an important role in this disease during the neonatal period. With this in mind, we compared thromboelastograms (TEG) from samples with and without urokinase (plasminogen-activator). In 13 out of 15 newborn infant blood-samples (prior to and after addition of urokinase) the thromboelastogram showed the pattern of a consumption coagulopathy. The change in the concentration of plasmin-inhibitor during the neonatal period was also measured using alpha2-macroglobulin, alpha1-antitrypsin and antithrombin III with M-partigen-plates. The value of alpha2-macroglobulin showed normal adult levels but the value of alpha1-antitrypsin and antithrombin III did not even reach half of the adult level. During the newborn period, the plasmin-inhibitor shows a remarkable lowering tendency and it may be surmised that with such a lowering tendency plasmin-inhibitor may constitute an exceptionally large handicap when the activator is working. This is especially true in the case of lung hemorrhage since the activator arises from a severe pathological state in the lungs and in addition because this is complicated by the lowering of plasmin-inhibitor. These results indicate that the low level of plasmin-inhibitors work synergistically with the high value of activator. The low level of antithrombin III could be the reason for coagulation disorders such as disseminated intravascular coagulation, (DIC).

Antithrombins↗

Off-pump coronary artery bypass surgery may produce a hypercoagulable patient.

BACKGROUND: The incidence of thromboembolic events following traditional open heart surgery has not been clinically significant. However, with beating heart surgery, for which cardiopulmonary bypass (CPB) is not required, the incidence of spontaneous intravascular thrombosis may be similar to that encountered after general surgeries. Compounding this risk is that many cases of off-pump coronary artery bypass (OPCAB) surgery are reserved for the elderly patient with multiple comorbidities. The few studies to date that have assessed the coagulation profile in OPCAB patients have been limited to the first 24 hours after surgery. METHODS: We prospectively studied 17 OPCAB and 6 onpump patients over 4 days (hospital course) with daily thromboelastography. A coagulation index (CI) (reflecting R and K times, angle, and maximum amplitude lbrack;MArbrack;) was calculated for the patients, who served as their own controls. RESULTS: The OPCAB patients demonstrated 3 days postoperatively a 17% increase in coagulation compared with the baseline. Specifically, the CI consistently revealed an elevation in the angle and the MA, both of which reflect increased fibrinogen and platelet activity. On the other hand, 3 days following surgery the CI of the CPB group was tightly clustered around their respective baseline CI values, which had recovered from a significant decrease immediately after surgery. CONCLUSION: A state of hypercoagulability, as measured by thromboelastography, exists in the OPCAB patient beyond the first postoperative day, and this finding suggests that prophylactic postoperative anticoagulation therapy targeting fibrinogen and platelet activity may be indicated for these patients.

Adult↗

Thromboelastography for the prediction of bleeding after transplant renal biopsy.

The ability of prebiopsy coagulation assays to predict mild postbiopsy bleeding was evaluated in renal transplant patients undergoing renal allograft biopsy (N = 120). The coagulation assays studied included the bleeding time, prothrombin time, partial thromboplastin time, platelet count, and thromboelastograph (TEG). Coagulation results were defined as abnormal if they fell outside the established normal reference range. Bleeding was defined as a drop in the hematocrit equal to or more than 4 points 6 h after the procedure or ultrasound evidence of a new perirenal hematoma. Overall, 21% of patients showed evidence of mild bleeding. Of those who bled, 78% had normal results on all coagulation tests, indicating that most mild bleeding was not associated with coagulation abnormalities. Of the assays tested, only abnormal TEG:angle (P < 0.01) and TEG:k (P < 0.04) values were associated with an increased risk of bleeding. Bleeding times were not predictive of an increased risk of postbiopsy bleeding; five patients had abnormal bleeding times ranging from 10 to 20 min of whom only one bled. All prothrombin time, partial thromboplastin time, and platelet count abnormalities were mild (e.g., no prothrombin times longer than 15 s, no platelet counts below 129,000/microL); none of these assays predicted postbiopsy bleeding. Other clinical characteristics, including patient age, sex, serum creatinine, blood pressure (if less than 160/90 mm Hg), number of biopsy passes, or renal pathology, did not appear to influence bleeding after biopsy. It was concluded that most bleeding after transplant renal biopsy was not associated with coagulation abnormalities and that the TEG was the best assay for detecting mild coagulation abnormalities associated with an increased risk of bleeding.

Biopsy↗

Evidence of hypercoagulability in dogs with parvoviral enteritis.

OBJECTIVE: To determine whether dogs with naturally occurring canine parvoviral (CPV) enteritis have laboratory evidence of hypercoagulability. DESIGN: Case-control study. Animals-9 dogs with naturally occurring CPV enteritis and 9 age-matched control dogs. PROCEDURE: Blood was collected from all dogs within 24 hours of admission for thromboelastography (TEG) and determination of activated partial thromboplastin time (aP-TT), prothrombin time (PT), antithrombin III (AT) activity, and fibrinogen concentration. Fibrin-fibrinogen degradation product (FDP) concentration, D-dimer concentration, and platelet count were obtained in dogs with CPV enteritis only. Records were reviewed for evidence of thrombosis or phlebitis. RESULTS: All 9 dogs with CPV enteritis had evidence of hypercoagulability, determined on the basis of significantly increased TEG maximum amplitude and decreased AT activity. Fibrinogen concentration was significantly higher in dogs with CPV enteritis than in control dogs. The aPTT was moderately prolonged in dogs with CPV enteritis, and FDP concentration was < 5 mg/ml in 7 of 9 dogs. No dogs had a measurable D-dimer concentration. Platelet counts were within reference range. Four of 9 dogs had clinical evidence of venous thrombosis or phlebitis associated with catheters. One dog had multifocal splenic thrombosis identified at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with CPV enteritis have a high prevalence of clinical thrombosis or phlebitis and laboratory evidence of hypercoagulability without disseminated intravascular coagulopathy. Thromboelastography may help identify hypercoagulable states in dogs.

Animals↗