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To establish whether asymptomatic normotensive pregnant women with an abnormal uterine Doppler velocimetry, have haematological changes characteristic of congenital or acquired thrombophilia, and whether this information improve predict in pregnancy complications.A prospective study involved the enrolment of 30 healthy normotensive pregnant women between the 23rd and 27th week of gestation, subdivided into group A (normal uterine Doppler velocimetry) and group B (abnormal uterine Doppler velocimetry). Besides uterine velocimetry (resistence index and presence/absence of notch), at enrolment in the study the PI of the umbilical artery and of the middle cerebral artery were measured, in addition to the usual foetal biometric parameters (biparietal diameter and abdominal circumference). Contemporaneously, a 20 ml blood sample was taken for the dosage of protein C, protein S, antithrombin III, activated protein C resistance, antiphospholipid antibodies and platelet functionality. Subsequently, for all the remaining period of the pregnancy, data were collected relating to the onset of any materno-foetal complications and modality of delivery, as well as neonatal data up to the first 20 days of life.The incidence of adverse perinatal outcomes (pre-eclampsia, gestational hypertension, abruptio placentae, endouterine foetal death, preterm birth, caesarean section because of maternal or foetal problems, APGAR score lower than 7 at the 5th minute of life, small for gestational age) resulted as being 75% in group B versus 11% in group A (P0.001). The mean gestational age at delivery was 34 weeks (range 27-41) in group A versus 39 weeks (range 37-42) in group B (P0.001). No difference emerged as to either the mean activity in the plasma levels of the coagulation protein studied in patients with normal and abnormal uterine velocimetry. The same consideration is also true if the population is analysed in relation to the lesser or greater seriousness of the Doppler velocimetry abnormalities. Subdividing the patients in relation to the absence and to the presence of unfavourable perinatal outcomes, the thrombophilic indices appear to be substantially comparable.Uterine Doppler velocimetry, carried out between the 24th and the 26th week of pregnancy, proves its validity by identifying a population at high risk of adverse perinatal outcomes. In contrast, the investigations carried out on the haematological abnormalities characteristic of thrombophilia do not reveal any significant differences, either between patients with normal and those with abnormal velocimetry, or between patients with adverse perinatal outcomes and those without. It is thus unlikely that these preliminary data will lead to an improvement in the clinical reliability of uterine velocimetry.

The constantly workload increase has led to the development of Computerised Decision Support Systems (CDSS) for a better management of patient care. Many clinical situations have been investigated to verify the utility of CDSS: few have demonstrated stable effects. One area where success has been reported is the field of oral anticoagulation management. CDSS system has demonstrated to be able to improve the treatment quality in comparison to manual method. In the future scenario of oral anticoagulant management CDSS will have a pivotal part, the constant increase of patients number and their pressure on thrombosis centres had led to the development of alternative models for delivery OAT: Primary care, General Practitioner, Patient self testing and self management and the use of CDSS has been central to the decentralisation process and may be useful in maintaining the efficacy and quality of anticoagulant control. GP with the aid of CDSS are able to deliver OAT as well as expert physician of Thrombosis Centre in terms of time spent by patient in therapeutic range.

Cerebral venous and sinus thrombosis (CVST) is still considered a severe clinical problem that is difficult to diagnose and manage and is linked to a poor prognosis. Nonetheless, conventional cerebral angiography and magnetic resonance imaging (MRI), or more recently, MR angiography allow a more rapid and precise diagnosis, and prognosis has improved with the use of anticoagulant treatment. We report 23 cases of CVST consecutively admitted to the Institute of Neurology of the University of Parma during the period 1990-1997. In all cases diagnosis was confirmed by means of MRI or conventional angiography of brain vessels. Among the patients, 22 were female and 1 was male. In all patients, plasma levels of protein C, protein S, antithrombin III (ATIII) and antiphospholipid antibodies (APA) were evaluated. In 15 of 23 patients, the presence of factor V Leiden mutation was also determined, and found positive in 3 patients (20%). Of the 22 female patients, 15 (68%) were on low-oestrogen (containing less than 50 microg oestrogen) oral contraceptive (OC) treatment. This percentage of OC use by patients with CVST is much higher than that of the rest of the female Italian population. OC use was associated with the presence of factor V Leiden mutation in two cases, with a deficiency of protein C in 1 case and a deficiency of protein S in another.Whether low-oestrogen Ocs may induce cerebral thromboembolic events is an open matter. According to our data, it may be argued that Ocs, even if at low oestrogen content, represent a major risk factor for CVST. The use of Ocs, as is the case for systemic venous thromboembolic events, may further increase the risk of CVST in women carrying the factor V Leiden mutation or other inherited hyperthrombotic conditions.

Heparin administration for operations with extracorporeal circulation (ECC) usually is performed following prefixed, standardized protocols. These regimens secure an adequate level of anticoagulation, hut they often involve prolonged periods of overheparinization associated with an undue risk of hemorrhage. The predictive value of preoperative studies on the anticoagulant effect of heparin was investigated in 10 patients. The study was performed both in vitro and in vivo using the Xa inhibitor assay as an index of the anticoagulation induced by heparin. Adding variable amounts of heparin in vitro to patient’s plasma resulted in straight (at least up to 7 U. per milliliter) and parallel, but not coincident, dose/response curves, so confirming a different individual sensitivity to heparin. Disappearance curves of the anticoagulant effect in plasma following intravenous administration of a single standard dose of heparin in the same patients showed an even greater patient-to-patient variability, with “half-life” times ranging from 30 to 150 minutes. No relationship was found between the two parameters (in vitro sensitivity to heparin and clearance rate from plasma in vivo). Moreover, neither of them could be correlated with the response to heparin, subsequently observed during ECC in the same patients. Preoperative investigations with the methods presently available are not adequate to choose individual heparin administration regimens for cardiac operations.

The efficacy and safety of pentoxifylline (400 mg tid orally) and aceno coumarol, administered singly or in combination, in the treatment of intermit tent claudication associated with chronic occlusive arterial disease were evaluated in a multi-center, randomized, factorial, blind clinical trial involving 146 patients. The response to treatment was assessed by measuring pain-free walking time on the treadmill and by Doppler ankle/arm systolic pressure ratio at rest and after treadmill. Both pentoxifylline and acenocoumarol were significantly more effective than placebo in increasing the proportion of patients who improved their per formance on the treadmill after one year of treatment. Benefit from active treatment was also apparent from the results of Doppler examinations per formed after physical exercise. No significant differences were observed in comparing the effect of one ac tive drug versus the other or versus the combined treatment. Five major hemorrhagic complications were registered in anticoagulated pa tients, two fatal cerebral hemorrhages and one gastrointestinal bleeding occur ring in the group treated with both active drugs. The investigators conclude that (1) pentoxifylline is effective and safe in the treatment of patients with intermittent claudication (2) the benefits of oral anti coagulant therapy are outweighed by the risk of serious bleeding, and (3) the risk of bleeding is probably increased by the combined treatment with pentox ifylline.

Deficiency of prostacyclin (PGI2) has been related to the pathogenesis of thrombotic thrombocytopenic purpura (TTP), and reduced PGI2 activity is thought to be secondary to a lack of plasma factor(s) which normally stimulates PGI2 production. We measured PGI2 production by means of the method of Moncada et al (Lancet 1:18, 1977), as platelet aggregation inhibitory activity released by venous specimen removed surgically in a 52 year-old woman with TTP in the acute phase of the disease. The patient was subsequently cured by plasma exchange.Platelet aggregation inhibitory activity released from venous tissues of the patient was normally detectable and comparable to that of a healthy control. Moreover, patient plasma was able to induce release of prostacyclin-like activity from exhausted veins (both from patient and normal control) as well as normal plasma. Hence release of PGI2 like activity from venous tissues and ability of plasma to stimulate prostacyclin synthesis in normal vascular tissues were not impaired in our patient with TTP in the acute phase of the disease.Our findings demonstrate that PGl2 deficiency is not implicated in the pathogenesis of all cases of TTP.

An inherited deficiency of antithrombin III (AT III), measured with four different, functional and immunological, methods, was found in 8 out of 11 examined members and in 3 out of 11 examined members of two Italian families (D.M. and A. families). Biological activity, measured with Abildgard’s clotting assay and with an amidolytic method, ranged between 17 and 75%. Cross immunoelectrophoresis, with or without heparin, performed in the two propositi and in 1; other relatives, showed a normal pattern of migration.A different behaviour of AT III after anticoagulation with acenocoumarin was seen in two long-term treated subjects. The proposita of the D.M. family, who had a history of recurrent thrombotic accidents, did not show any increase of AT III levels, measured in the first two weeks and after 6 and 12 months of therapy. A significant (about 50%) increase both with the functional and immunological methods was on the contrary observed in the propositus of A. family, who had undergone surgery because of mesenteric vein thrombosis. Until now both patients have been free of thrombotic recurrences.Our findings confirm previous reports of variable effects of oral anticoagulants on AT III levels in subjects with congenital deficiency.

Three substances widely used as vasoactive drugs are known to have an inhibiting effect on platelet aggregation ‘in vitro’. We investigated the changes induced on thrombelastogram, routine clotting tests, euglobulin lysis time (ELT), platelet count, aggregation, and adhesiveness by i, v. administration of these drugs to man. The same indices were also studied ‘in vitro’ by adding comparable concentrations of the substances to human blood or plasma.Aminophilline did not produce any significant variation in ADP-or collagen-induced aggregation either ‘in vitro’ (50 to 200 μg/ml) or ‘in vivo’ (240 mg). A trend to disaggregation was seen only in a few cases. Shorter ELT were found 30 and 120 minutes after injection.A papaverine derivative (Metaverinum, 150 mg) showed a similar ‘in vivo’ pattern: minor changes in platelet function tests and a moderate activation of fibrinolysis were seen. The drug acted ‘in vitro’ as a powerful inhibitor of aggregation (from 30 µg/ml)while fibrinolysis was only activated at the highest concentration (120 µg/ml).Bencyclan, capable of inhibiting platelet function ‘in vitro’ at very low concentrations (0.25µM) did not show similar effects ‘in vivo’ (50 mg) apart from a reduced platelet adhesiveness to glass.