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Biomedical subjects

M Cattaneo

Publications and source records attributed to M Cattaneo.

At least 91 records · Page 5Linked to original sources
PubMed1995

Platelet aggregation at high shear is impaired in patients with congenital defects of platelet secretion and is corrected by DDAVP: correlation with the bleeding time.

Techniques measuring platelet aggregation in vitro under the high shear rate conditions that can be found in the microcirculation could reflect the status of primary hemostasis better than the turbidimetric technique. We studied platelet aggregation at high shear in patients with prolonged bleeding time caused by congenital platelet secretion defects such as delta-storage pool deficiency and primary secretion defect. Two different techniques were used: shear-induced platelet aggregation in a cone-and-plate viscometer and the filter aggregation test. With both techniques, platelet aggregation at high shear rate was defective in 14 patients with delta-storage pool deficiency and in 8 with primary secretion defect. There was a statistically significant correlation between platelet aggregation at high shear rate and the bleeding time. In patients with delta-storage pool deficiency, platelet aggregation at high shear rate and the bleeding time were significantly correlated with the platelet serotonin content. The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) (0.3 micrograms/kg) increased the plasma concentration of von Willebrand factor (vWf), shortened the bleeding time, and potentiated platelet aggregation at high shear rate in all patients. Because platelet aggregation at high shear rate requires vWf, the effect of DDAVP is probably due to the induced increase in plasma vWf. Therefore, platelet aggregation at high shear rate is defective in patients with congenital defects of platelet secretion and is potentiated by DDAVP. Potentiation of platelet aggregation at high shear rate may be one mechanism by which DDAVP shortens the prolonged bleeding time of patients with congenital defects of platelet secretion.

Bleeding Time↗
PubMed1995

The effect of desmopressin on reducing blood loss in cardiac surgery--a meta-analysis of double-blind, placebo-controlled trials.

The effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (> 1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

Adult↗
PubMed1994

Patients with severe von Willebrand disease are insensitive to the releasing effect of DDAVP: evidence that the DDAVP-induced increase in plasma factor VIII is not secondary to the increase in plasma von Willebrand factor.

It is generally held that factor VIII (FVIII) does not increase in the plasma of severe von Willebrand disease (vWD) patients treated with DDAVP because they lack von Willebrand factor (vWF), which is the plasma carrier for FVIII. To test this hypothesis, FVIII plasma levels were monitored in severe vWD patients treated with DDAVP after normalization of vWF plasma levels with infusions of cryoprecipitate. Each of four severe vWD patients underwent four different treatments at intervals of at least 15 d: (1) cryoprecipitate plus DDAVP; (2) cryoprecipitate plus saline; (3) cryoprecipitate plus recombinant FVIII (rFVIII); (4) saline plus rFVIII. Cryoprecipitate increased the plasma levels of FVIII and vWF. The infusions of saline or DDAVP after cryoprecipitate did not further increase FVIII and vWF plasma levels and had no effect on the plasma levels of tissue plasminogen activator (tPA), which are raised by DDAVP in normal subjects and in patients with vWD of other types. The infusion of rFVIII further increased by 182 +/- 32 U/dl (mean +/- SEM) the plasma levels attained after cryoprecipitate, which disappeared from the circulation with a half-life of 11.95 +/- 0.86 h. In contrast, the infusion of rFVIII after saline increased by only 107 +/- 18 U/dl the plasma levels of FVIII, which disappeared from the circulation with a half-life of 2.68 +/- 0.14 h, indicating that the vWF infused with cryoprecipitate is able to bind additional FVIII. These studies indicate that DDAVP does not increase the plasma levels of FVIII in patients with severe vWD even after normalization of plasma vWF. The possibility is discussed that severe vWD patients may be insensitive to the releasing effect of DDAVP.

Deamino Arginine Vasopressin↗
PubMed1994

Role of ADP in platelet aggregation at high shear: studies in a patient with congenital defect of platelet responses to ADP.

The in vitro measurement of platelet aggregation (PA) at the high shear levels that can be found in the microcirculation may provide useful informations on primary haemostasis, which is usually explored in vivo with the skin bleeding time (BT). PA at high shear requires von Willebrand factor (vWf) and the platelet glycoprotein (GP) complexes Ib/IX/V and IIb/IIIa; controversial results have been reported on its requirement of released adenosine diphosphate (ADP). Due to its dependence on vWf, PA at high shear may be affected by the vasopressin analogue DDAVP, which increases the plasma vWf levels and shortens the prolonged BT of patients with congenital or acquired defects of platelet function. We studied PA at high shear, BT and plasma vWf levels in a patient with congenital impairment of platelet responses to ADP before and after the i.v. infusion of 0.3 micrograms/kg DDAVP. Two methods to study PA at high shear were used: shear-induced PA (SIPA) and the filter aggregation test. With both methods, PA at high shear of the patient was impaired. The infusion of DDAVP increased plasma vWf levels, shortened the prolonged BT and potentiated PA at high shear of the patient. In conclusion, PA at high shear is impaired in a patient with congenital defect of platelet responses to ADP and prolonged BT and is potentiated by DDAVP. Our results suggest that released ADP plays an important role in PA at high shear and that potentiation of PA at high shear by DDAVP may be one mechanism by which the drug shortens the prolonged BT of patients with congenital or acquired defects of platelet function.

Adenosine Diphosphate↗
PubMed1994

High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis.

We determined the prevalence of hyperhomocyst(e)inemia before and 4 hours after a methionine load (3.8 g/m2) in 80 patients (25 mean and 55 women) who had had at least one verified episode of venous thromboembolism before the age of 40 years and in 51 healthy control subjects. No patient had any of the hemostatic abnormalities known to be associated with increased risk of venous thrombosis, and all had normal renal and liver function and no evidence of neoplastic disease. Hyperhomocyst(e)inemia was defined as fasting plasma homocyst(e)ine levels or absolute postload increments of homocyst(e)ine above the normal range. According to these diagnostic criteria, 15 patients (18.8%) and 1 control subject (1.9%) had hyperhomocyst(e)inemia. In 1 of these patients only, hyperhomocyst(e)inemia could be explained by low serum concentrations of vitamin B12 and folates. The family history for venous thromboembolism was positive for 7 of the 15 patients. Family studies, performed for eight kindreds, showed that for more than half of the studied probands the abnormality was inherited. This study indicates that moderate hyperhomocyst(e)inemia is associated with an increased risk of developing venous thromboembolism at a young age and that measurements of fasting and postmethionine plasma homocyst(e)ine levels may be useful in the evaluation of patients with juvenile venous thromboembolism, particularly if their family history suggests the presence of an inherited abnormality.

Administration, Oral↗
PubMed1994

Persistent activation of coagulation mechanism in unstable angina and myocardial infarction.

BACKGROUND: The blood coagulation system is activated in the acute phase of unstable angina and acute myocardial infarction. However, it remains unclear whether augmented function of the hemostatic mechanism serves only as a marker of the acute thrombotic episode or whether a hypercoagulable state persists for a prolonged period after clinical stabilization. METHODS AND RESULTS: We prospectively measured the plasma concentrations of prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) in consecutive patients presenting with unstable angina (n = 81) or acute myocardial infarction (n = 32), respectively. At 6 months, plasma determinations were repeated in patients experiencing an uneventful clinical course (unstable angina, n = 57; myocardial infarction, n = 23). We quantitated the plasma levels of F1 + 2 and FPA in control patients with stable angina (n = 37) or healthy individuals (n = 32) who were matched for age and sex. The median plasma concentrations of F1 + 2 and FPA are significantly higher in patients presenting with unstable angina (F1 + 2, 1.08 nmol/L; FPA, 2.4 nmol/L) or acute myocardial infarction (F1 + 2, 1.27 nmol/L; FPA, 3.55 nmol/L) compared with patients with stable angina (F1 + 2, 0.74 nmol/L; FPA, 1.3 nmol/L; P < .0001) or healthy individuals (F1 + 2, 0.71 nmol/L; FPA, 0.80 nmol/L; P < .0001). At 6 months, the median plasma levels of F1 + 2 in patients exhibiting an uneventful clinical course did not differ from values obtained at admission (unstable angina, 1.26 versus 1.07 nmol/L, P = NS; myocardial infarction, 1.22 versus 1.29 nmol/L, P = NS), whereas the median plasma levels of FPA in the same two subpopulations were significantly reduced (unstable angina, 1.1 versus 2.9 nmol/L, P = .0003; myocardial infarction, 1.1 versus 3.0 nmol/L; P = .0028). CONCLUSIONS: During the acute phase of unstable angina and myocardial infarction, patients exhibit increased coagulation system activity. Over the next 6 months, patients with unstable angina or myocardial infarction experiencing an uneventful clinical course manifest a persistent hypercoagulable state with minimal generation of fibrin.

Adult↗
PubMed1994

Ticlopidine facilitates the deaggregation of human platelets aggregated by thrombin.

Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80-90% 14C-serotonin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5x the activity of thrombin) and PGE1 (10 mumol/l) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 mumol/l) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Adenosine Diphosphate↗
PubMed1993

Activation of the hemostatic system during thrombolytic therapy.

Activation of the hemostatic mechanism has been described during thrombolytic therapy. This phenomenon has been detected by new methods of assessing hemostatic system function, based on immunoenzymatic or radioimmunoassays. However, these methods are extremely sensitive and, unless they are performed in expert laboratories, carefully following the recommended procedures, they generate in vitro artifacts. A description of these methods is provided, as well as a critical review of the available studies. The correct use of these methods will provide us with an understanding of the complex response of the hemostatic system to pharmacologic thrombolysis.

Animals↗
PubMed1993

The in vitro production of thromboxane B2 by platelets of diabetic patients is normal at physiological concentrations of ionized calcium.

Platelets of patients with diabetes and no evidence of macroangiopathy produce normal amounts of thromboxane (Tx) B2 in vivo, whereas they usually show increased production in vitro. Since in vitro studies have been usually performed in citrated PRP, we tested the hypothesis that the discrepancy between in vivo and in vitro studies is due to the low concentration of plasma ionized calcium ([Ca2+]o) that is present in citrated PRP. In fact, low [Ca2+]o artifactually potentiates the platelet TxB2 production in vitro. Forty patients with diabetes mellitus and 37 matched controls were studied. Blood was anticoagulated with citrate, the thrombin inhibitor D-phenylalanyl-l-prolyl-l-chloromethylketone (PPACK) or both anticoagulants. Platelet aggregation, release of 14C-serotonin and TxB2 production were induced in platelet rich plasma (PRP) by several agonists. The following results were obtained: i) Citrated PRP: Arachidonic acid induced aggregation (p < 0.01) and TxB2 production (p < 0.02) were significantly greater in patients than in controls. No statistically significant differences were found with other agonists. ii) PPACK PRP: No statistically significant difference was found between diabetic platelets and controls. iii) PPACK plus citrate PRP: The results were not different from those obtained with citrate alone. Therefore, our results show that diabetic platelets produce normal amounts of TxB2 in vitro when the [Ca2+]o is physiological.

Adult↗
PubMed1993

[The Swiss population and drug problems: perception of the problems and proposals for solutions].

The aim of this study is to investigate which problems in relation with drug abuse are considered to be the most important by the Swiss population and which measures do they support to reduce them. Base for this study are the results of a representative telephone survey realized in october 1991 with 1004 Swiss residents. People are mostly concerned with problems related to the danger for youth and those concerning public order but also with the human condition of addicts. Drug addicts are considered as people who have lost the sense of live, as sick but also as dangerous and less truthful. Supported are overall prevention, offers for therapies, the repression of trafficking and money-laundering but not of drug users as well as measures going in the direction of harm-minimisation (shooting rooms, medical prescription of drugs). Younger people, those with higher education and the german-speaking population have a more positive view of drug addicts and support measures in the sense of harm-minimisation. Elder people and the french-speaking population have a rather negative view of drug addicts and don't favour measures for harm-minimisation.

Adolescent↗
PubMed1993

Shear-induced platelet aggregation is potentiated by desmopressin and inhibited by ticlopidine.

Shear-induced platelet aggregation is important in physiological hemostasis and in the pathogenesis of arterial thrombosis. It requires extracellular Ca2+, platelet membrane glycoproteins Ib/IX and IIb/IIIa, von Willebrand factor (vWF), and ADP. We studied the effects of desmopressin (DDAVP), which increases plasma vWF levels and shortens the bleeding time, and of ticlopidine, which inhibits platelet responses to ADP, on shear-induced platelet aggregation. Eleven healthy volunteers were given oral ticlopidine (250 mg b.i.d.) for 7 days. The same subjects were infused intravenously with DDAVP (0.3 micrograms/kg body wt) before the first and after the last doses of ticlopidine. The degree of platelet aggregation induced by shear stress at 25, 50, 75, and 100 dyne/cm2 in a cone-and-plate viscometer, plasma vWF levels, and the bleeding time were measured before and after each DDAVP infusion. Plasma vWF levels and the extent of shear-induced platelet aggregation increased after DDAVP and were correlated. Ticlopidine partially inhibited shear-induced platelet aggregation both before and after DDAVP infusion. The bleeding time, prolonged by ticlopidine, was shortened by DDAVP. Potentiation by DDAVP of shear-induced platelet aggregation may be one mechanism by which the drug shortens the prolonged bleeding time. Since shear-induced platelet aggregation can cause thrombotic occlusions in stenotic arterial vessels, our findings may explain the therapeutic efficacy of ticlopidine in arterial thrombosis.

Adult↗
PubMed1992

Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate.

This study characterizes a congenital hemorrhagic disorder caused by a platelet function defect with the following features: (1) severely impaired platelet aggregation and fibrinogen or von Willebrand factor (vWF) binding induced by adenosine diphosphate (ADP); (2) defective aggregation, release reaction, and fibrinogen or vWF binding induced by other agonists; (3) normal aggregation and release reaction induced by high concentrations of thrombin or collagen; (4) no further inhibition by ADP scavengers of aggregation, release reaction, and fibrinogen or vWF binding, comparable with those observed for normal platelets in the presence of ADP scavengers; (5) normal membrane glycoprotein (GP) composition and normal binding of the anti-GP IIb/IIIa monoclonal antibody 10E5; (6) no acceleration by ADP of binding of the anti-GP IIb/IIIa monoclonal antibody 7E3; (7) normal platelet-fibrin clot retraction if induced by thrombin or reptilase plus epinephrine, absent if induced by reptilase plus ADP; (8) no inhibition by ADP of the prostaglandin E1-induced increase in platelet cyclic adenosine monophosphate, but normal inhibition by epinephrine; (9) defective mobilization of cytoplasmic Ca2+ by ADP; (10) normal binding of 14C-ADP to fresh platelets, but defective binding of [2-3H]-ADP to formalin-fixed platelets. This congenital platelet function defect is characterized by selective impairment of platelet responses to ADP, caused by either decreased number of platelet ADP receptors or abnormalities of the signal-transduction pathway of platelet activation by ADP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Lack of stability of aggregates after thrombin-induced reaggregation of thrombin-degranulated platelets.

The stability of platelet aggregates is influenced by the extent of the release of granule contents; if release is extensive and aggregation is prolonged, deaggregation is difficult to achieve. The relative importance of the contributions of released substances to aggregate stability are not known, although stable thrombin-induced aggregates form in platelet-rich plasma from patients with barely detectable plasma or platelet fibrinogen, and ADP stabilizes thrombin-induced aggregates of platelets from patients with delta storage pool deficiency which otherwise deaggregate more readily than normal platelets. We degranulated platelets with thrombin (0.9 U/ml caused greater than 90% loss of delta and alpha granule contents) and recovered them as individual platelets in fresh medium. The degranulated platelets were reaggregated by thrombin (2 U/ml). To prevent continuing effects of thrombin, FPRCH2Cl was added when thrombin-induced aggregation of thrombin-degranulated platelets reached its maximum. EDTA (5 mM) or EGTA (5 mM) added at maximum aggregation did not deaggregate these platelets, indicating that the stability of these aggregates does not depend on Ca2+ in the medium. Whereas with control platelets a combination of PGE1 (10 microM) and chymotrypsin (10 U/ml) was required for deaggregation, with thrombin-degranulated platelets either PGE1 or chymotrypsin alone caused extensive deaggregation. The rate and extent of deaggregation of thrombin-degranulated platelets by a combination of PGE1 and chymotrypsin was greater than with control platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1992

Patterns of development of tachyphylaxis in patients with haemophilia and von Willebrand disease after repeated doses of desmopressin (DDAVP).

When patients with mild haemophilia or von Willebrand disease (vWD) are repeatedly treated with desmopressin (DDAVP) at relatively short time intervals, some of them may become less responsive or unresponsive. The development of tachyphylaxis would limit the usefulness of DDAVP in clinical management of these patients. On the other hand, tachyphylaxis is not consistent, and its patterns of development are unknown. The aim of this study was to evaluate in controlled conditions the occurrence of tachyphylaxis by giving intravenous DDAVP (0.3 microgram/kg) on four consecutive days to a selected group of patients with mild haemophilia A (n = 22) and type I vWD (n = 15). After each dose, we measured parameters known to change after DDAVP, i.e. factor VIII coagulant activity, bleeding time, von Willebrand factor antigen, ristocetin cofactor and tissue-type plasminogen activator antigen. We found that on average the responses obtained after the second dose of DDAVP were approximately 30% less than those obtained after the first, but were not further reduced after the third and fourth dose. At all time intervals after DDAVP, patients with vWD responded relatively better than patients with haemophilia, and there were fewer vWD patients who responded poorly or became unresponsive. In vWD patients there were no significant changes in the bleeding time responses and in blood pressure and heart rate. The clinical implications of these findings are that repeated doses of DDAVP can be given efficaciously to many patients (particularly to those with vWD), even though responses lower than those seen after the first dose should be expected.

Adult↗
PubMed1992

Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma.

We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6-4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended.

Adult↗