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Biomedical subjects

J W Ten Cate

Publications and source records attributed to J W Ten Cate.

At least 19 recordsLinked to original sources
PubMed1995

Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades.

1. Disseminated intravascular coagulation frequently accompanies Gram-negative sepsis and may contribute to widespread deposition of microthrombi. Besides the endotoxin-induced activation of coagulation, an important role for the fibrinolytic system has been postulated. The precise mechanisms underlying these fibrinolytic changes during endotoxaemia are not known but have been suggested to be mediated directly by cytokines or secondary to thrombin generation. 2. In the present study we have delineated in detail the fibrinolytic response to a bolus injection of endotoxin in non-human primates and analysed the contribution of cytokines and thrombin generation to the endotoxin-induced release of tissue-type plasminogen activator and plasminogen activator inhibitor 1. Chimpanzees received a bolus injection of endotoxin alone or in combination with blocking monoclonal antibodies directed against tumour necrosis factor or interleukin 6 or in combination with pentoxifylline. Furthermore, to assess the effect of coagulation activation on the activation of fibrinolysis, another group of chimpanzees received endotoxin in combination with either anti-tissue factor antibodies or recombinant hirudin. 3. Infusion of endotoxin induced a rapid increase in plasminogen activator activity and tissue-type plasminogen activator antigen levels and subsequent plasmin generation, reaching peak levels 2h after endotoxin administration. Plasminogen activator inhibitor 1 levels remained constant for the first 2 h, after which time a steep increase was observed. Plasminogen activator activity and plasmin generation decreased simultaneously with the rise in plasminogen activator inhibitor 1 levels. Fibrinolytic activity remained suppressed during the remainder of the study owing to sustained increased levels of plasminogen activator inhibitor 1. The administration of pentoxifylline strongly attenuated the release of tissue-type plasminogen activator and plasminogen activator inhibitor 1, whereas the antitumour necrosis factor antibodies blocked the fibrinolytic response entirely. In contrast, interleukin 6-neutralizing antibodies did not affect the fibrinolytic response. Although endotoxin-induced generation of thrombin was completely prevented by the administration of tissue factor-neutralizing antibodies or by hirudin, no effect on the fibrinolytic response was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The pharmacokinetics and pharmacodynamics of dermatan sulphate MF701 during haemodialysis for chronic renal failure.

Single i.v. bolus doses of dermatan sulphate MF701 were administered before the onset of haemodialysis to patients with chronic renal failure, to prevent clotting in the extracorporeal circuit. Six patients received 2 mg kg-1; six were given 2.5 and 3 mg kg-1; 13 received 4.5 and 6 mg kg-1. Plasma MF701 concentrations (chromogenic assay), activated partial thromboplastin time (APTT) and plasma markers of coagulation and platelet activation (TAT and beta-TG) were measured over 4 or 8 h from the onset of dialysis. The disposition of MF701 was described by a monoexponential function. C(0) and AUC values increased proportionally with dose. Volumes of distribution (approximately 4 l) were dose-independent. Half-lives showed a non significant increase with dose (from 2.2 to 3.1 h) and were 2.5-3 times longer than those reported for healthy subjects. There was a significant correlation between plasma MF701 concentration and its effects in prolonging APTT and suppressing TAT and beta-TG generation during dialysis.

Adult↗
PubMed1990

Vinculin is a permanent component of the membrane skeleton and is incorporated into the (re)organising cytoskeleton upon platelet activation.

Vinculin, a 130-kDa protein discovered in chicken gizzard smooth-muscle cells and subsequently also described in platelets, is believed to be involved in membrane-cytoskeleton interactions. In this study we investigated vinculin distribution in human blood platelets. Two skeletal fractions and a remaining cytosolic fraction were prepared with a recently described Triton X-100 lysis buffer causing minimal post-lysis breakdown by proteolysis. The presence of vinculin was demonstrated in the membrane skeleton and cytosol of resting and thrombin-activated human platelets. Upon thrombin stimulation vinculin also appeared in the cytoskeleton. this cytoskeletal incorporation was completed during the early stages of platelet aggregation and secretion, when the uptake of myosin, actin-binding protein and talin was still not maximal. We conclude therefore, that vinculin may play an important role in the structural (re)organisation of the human platelet cytoskeleton upon platelet activation.

Blood Platelets↗
PubMed1989

Severe thrombotic tendency associated with a type I plasminogen deficiency.

We report a 45-year-old female patient with recurrent spontaneous deep vein thrombosis associated with an isolated hypoplasminogenemia (plasminogen activity and antigen level of 42% and 37%, respectively). The plasminogen molecule was normal as demonstrated by a normal activation by tissue plasminogen activator, electrophoretic mobility on crossed immunoelectrophoresis, molecular weight, and binding to lysine sepharose. All other hemostatic parameters predisposing to recurrent thrombosis were normal. A stimulation test with desmopressin acetate (DDAVP) showed a normal plasma rise of both tissue plasminogen activator and factor VIIIR:WF. This isolated plasminogen deficiency apparently is due to a decreased synthesis of a normal plasminogen molecule and is associated with a severe thrombotic tendency.

Deamino Arginine Vasopressin↗
PubMed1988

The influence of epidural analgesia on platelet function and correlation with plasma bupivacaine concentrations.

The effect of epidural anaesthesia with bupivacaine 0.5% on platelet aggregation was studied in seven patients undergoing transurethral resection of the prostate. Peak plasma concentrations of bupivacaine 470 +/- 270 ng ml-1 occurred at 30 min after administration. At that time there were no significant changes in platelet aggregation. However, the maximum rate of the primary- and secondary-aggregation velocities induced by 1.0 microM ADP were significantly decreased at 1 h and 3 h after bupivacaine administration. The maximum percentage ADP-induced platelet aggregation was also decreased significantly at 1 h and 3 h. The minimum concentration of ADP required to induce secondary-phase platelet aggregation was significantly increased at 1 h but not at 3 h. There was a significant correlation between bupivacaine concentrations and all platelet aggregation parameters except the maximum ADP-induced aggregation. Platelet inhibition occurred at plasma bupivacaine concentrations that were considerably lower than those needed to produce similar inhibition in vitro.

Adenosine Diphosphate↗
PubMed1985

A randomized blind study comparing standard heparin and a new low molecular weight heparinoid in cardiopulmonary bypass surgery in dogs.

Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated.

Animals↗
PubMed1984

Antithrombin III levels in preeclampsia correlate with maternal and fetal morbidity.

In 57 patients with pregnancy-induced or aggravated hypertension, antithrombin III levels correlated inversely with maternal morbidity. Morbidity was determined by the maximal diastolic blood pressure, disturbance of renal and liver function, and thrombocytopenia. Antithrombin III levels and platelet counts correlated inversely with the degree of placental infarction. Proteinuria (grams per 24 hours) was most predictive of fetal outcome, which was considered to be either favorable if a healthy baby could be discharged with its mother or unfavorable in case of perinatal death or a prolonged stay in the neonatal intensive care unit. Plasma antithrombin III and serum glutamic oxaloacetic transaminase levels, in that order, augmented the number of correct predictions. Antithrombin III inhibits blood coagulation by forming irreversible complexes with activated clotting enzymes, notably with factor Xa and thrombin. Evidence is presented which suggests that antithrombin III levels in preeclampsia are depressed as a result of increased consumption in the maternal vascular tree, rather than decreased synthesis or increased urinary loss.

Adult↗
PubMed1984

Antithrombin III metabolism in patients with liver disease.

Liver diseases are associated with complex haemostasis defects, in which platelets, coagulation, and fibrinolysis may all be affected. The low plasma concentrations of clotting factors often found can be the result of many changes such as impaired synthesis, increased catabolism due to intravascular coagulation, or alternate distribution. In this study, we investigated the metabolism of purified human antithrombin III(AT III) labelled with 125I in 25 patients with histologically established liver disease and in nine control subjects. The results showed that, in general, low plasma concentrations of AT III in liver cirrhosis are not due to consumption in the central compartment but rather to altered transcapillary flux ratio. Such altered transcapillary flux ratios may already exist even with normal plasma AT III concentrations. Altered ratios are not only found for coagulation proteins but also for albumin and thus may be a general phenomenon of liver disease. In micronodular cirrhosis the alpha phase, the transcapillary efflux (k1, 2) and influx (k2, 1) were significantly increased compared with the normal subjects.

Antithrombin III↗
PubMed1984

Low antithrombin III levels in neonates with idiopathic respiratory distress syndrome: poor prognosis.

Automated microanalytic chromogenic coagulation assays allow serial monitoring of critically ill newborn infants. In this study 84 premature infants [26 healthy prematures and 58 neonates with idiopathic respiratory distress syndrome (IRDS)] were studied daily during the first week of life, to investigate the possible significance of hemostatic abnormalities in IRDS. In neonates with IRDS, coagulation factors II and X, antithrombin III (AT-III), plasminogen, and alpha 2-antiplasmin were significantly lower than control values. Recovery of the initially low AT-III levels was delayed relative to the other coagulation parameters measured. An AT-III less than or equal to 0.15 U/ml was present within the first 6 h of life in eight patients who developed IRDS, seven of whom died within 48 h. Autopsy of these neonates showed widespread fibrin deposition and hemorrhage in vital organs consistent with intravascular coagulation. These findings indicate that very low levels of AT-III are associated with disseminated intravascular coagulation in neonates with IRDS and suggest that a deficiency of AT-III is predictive of a poor outcome.

Antithrombin III Deficiency↗
PubMed1983

Use of a new heparinoid as anticoagulant during acute haemodialysis of patients with bleeding complications.

Org 10172, a new, natural heparinoid, was used as the sole anticoagulant in twelve patients with acute or acute-on-chronic renal failure, who underwent haemodialysis 55 times. All patients had either intercurrent bleeding or a high risk of severe haemorrhagic complications if given standard heparin therapy. After a single loading dose of 300-600 mg of Org 10172, plasma anti-Xa levels in the range 0.42 - 0.93 U/ml were achieved. All haemodialysis runs were completed without adverse side-effects. There were no haemorrhagic complications and deposition of 125I-fibrinogen on the renal dialysis membrane was successfully inhibited in the 4 patients in whom this was studied. Org 10172 seems to prevent thrombosis during renal haemodialysis. It may have a lower risk/benefit ratio than other anticoagulants, such as heparin, in patients at high risk of haemorrhagic complications undergoing haemodialysis.

Acute Kidney Injury↗
PubMed1983

No evidence for a prethrombotic state in stable chronic inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are associated with a high risk of thromboembolic complications. The questions whether reported risk factors such as low antithrombin III concentrations, thrombocytosis and spontaneous platelet aggregation are merely related to the activity of the inflammatory process remains to be answered. Therefore we investigated 40 patients with an established colitis or Crohn's disease, without signs of active inflammation (normal history, normal ESR and leucocyte count). Of these patients only one patient revealed thrombocytosis, six patients spontaneous platelet aggregation. All patients had normal beta-thromboglobulin and platelet factor 4 plasma levels. No other prethrombotic abnormalities were encountered. There was normal factor VIII C (increased in three patients), normal VIII C/VIII R Ag ratio (1.2), antithrombin III, normal plasminogen and normal alpha 2-antiplasmin. Normal fibrinopeptide A and B beta (15-42) plasma levels (n = 15) in these patients excluded in vivo thrombin or plasmin generation. We conclude that stable chronic inflammatory bowel disease is in general not associated with prethrombotic coagulation abnormalities.

Adolescent↗
PubMed1983

Antithrombin III levels in normotensive and hypertensive pregnancy.

Antithrombin III (AT III) is the main physiological inhibitor of blood coagulation. In a prospective study, plasma AT III was determined in 653 women during pregnancy, using an automated amidolytic technique. A control value 8 weeks after delivery was obtained in 192 of the women. In women with pregnancy-induced or aggravated hypertension a significant decrease in AT III levels was observed compared with normotensive controls of the same period of gestation and compared with the patients' own control values 6-8 weeks after delivery. No AT III depression occurred in patients with chronic hypertension during pregnancy. Patients with pregnancy hypertension and proteinuria had lower AT III levels than those without proteinuria, whose AT III levels were also depressed. Lowest AT III levels were seen in 2 eclamptic patients and in patients with severe preeclampsia, whose pregnancies were terminated for fetal distress while the infants were still preterm. Monitoring At III levels is of value in preeclampsia.

Adult↗