The prevalence of AIDS, AIDS related complex and HIV seropositivity in a large population of patients with congenital clotting disorders.

We have investigated up to the beginning of 1987 114 patients with congenital clotting disorders. 84 had received plasma and/or clotting factors concentrates. 18 out of 84 (21%) had leukopenia, thrombocytopenia, or both. 64 out of 84 (76%) had been infected by hepatitis B virus. The great majority of them (62 out 64) developed adequate immunity (anti Hbs antibodies). Despite this, 47 out 84 (57%) showed persistently elevated transaminases. 17 out of 84 (20%) had HIV-seropositivity. Among them, 7 are free of symptoms related to such a virus up to present time, 8 developed AIDS-related complex and 2 had the full-blown AIDS and died. Non significant difference in HIV seroconversion or its clinical manifestations was noted depending on the administration of factor VIII concentrates versus prothrombin complex concentrates. In contrast, plasma administration appeared to be associated with a lower risk of viral transmission. No abnormality was observed in patients who had never received haemoderivatives, except the presence of anti Hbs antibodies in 1 of them.

Lack of antiplatelet activity of the new coumarin derivative 8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carboxylmethoxycoumarin under in vivo conditions in man.

Antiplatelet properties of AD 6 (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy-carboxyl- methoxycoumarin) have been studied in vitro and in vivo. The drug showed a marked inhibitory effect on platelet aggregation, beta-thromboglobulin (beta TG) release and thromboxane B2 (TxB2) production in vitro. However, such effects were seen only in the presence of high concentrations of the drug (10(-3) and 10(-4) mol/l) and completely disappeared at lower concentrations. No effect was seen in vivo following oral administration of 300 mg of the drug in a small group of volunteers. It can be concluded that in vitro properties of the drug cannot be surmised without due caution to indicate its potential clinical use.

First case in Italy of fatal AIDS in a hemophiliac.

The first fatal case of AIDS in an hemophiliac observed in Italy is reported. The propositus is a 53-year-old hemophilia A patient who died on the 8th December, 1984. AIDS was documented clinically and in the laboratory by serum antibodies to HTLV-III detected by ELISA and Western blot assays. A progressive intellectual worsening of the patient due to diffuse cerebral atrophy was followed by CT scan, EEG and by evaluation of proper neurological signs and symptoms.

Dental extraction in congenital hemorrhagic patients.

125 dental extractions were performed in patients with hemophilia A, B, von Willebrand disease and rare coagulopathies. The missing factor was brought to a level of 15-40% according to the degree of surgical trauma. In the majority of cases a single pre-extraction administration of concentrate was sufficient. Antifibrinolytics were administered to the patients (tranexamic acid, 60 mg/kg/day) for 8-10 days. After tooth extraction, a fibrin sponge was positioned using anti-traumatic cross suture. In 90% of cases there was no bleeding, in the others modest easily controllable hemorrhagic episodes. Our results show that it is sufficient in hemophilia A and B to use low doses of antihemophilic concentrate (10-20 U/kg) and frequently a single pre-extraction administration. In rare coagulopathies the hemostatic procedure and dental management have also to be similar to those used in hemophilia A and B.

Further studies on the hypercoagulable state of patients with Cushing's syndrome.

Factors XII, XI, IX and VIII, plasminogen and alpha 2-antiplasmin levels were found to be increased in a group of patients affected by Cushing's syndrome. High activity of these coagulation factors could be due to their increased release and synthesis mediated by cortisol. A significant correlation between the main arterial pressure and either factor VIII antigen, ristocetin cofactor or factor XII activity was found. Moreover a similar correlation between factor XII activity and either factor VIII antigen or ristocetin cofactor was seen. In conclusion, the presence of a hypercoagulable state in Cushing's syndrome seems confirmed. Synergic release of factor XII and factor VIII from endothelium could be due to high blood vessel tone secondary to hypercorticism. Finally, decreased fibrinolytic activity was suspected according to plasminogen and alpha 2-antiplasmin increase.

The importance of simple coagulation tests (fibrinogen assays and thrombin coagulase clotting time) in the diagnosis of liver cancer.

Dysfibrinogenemia in 36 patients with primary hepatocarcinoma and in 25 patients with cirrhosis of the liver was studied by means of reptilase time, thrombin coagulase time, fibrin polymerization and fibrinogen assays. Both groups of patients were similar in age, sex and incidence of HBs Ag. No electrolyte or fluid imbalances were present. Prolonged reptilase time and prolonged polymerization time were found in both groups; however, thrombin coagulase time was prolonged in 80% of the hepatocarcinoma group, but was normal in almost all patients with cirrhosis (p less than 0.001). In the hepatocarcinoma group, a difference of more than 100 mg per 100 ml was present between the immunologic and coagulative methods of fibrinogen determination in 36.1% of the cases, but in the cirrhotic group this difference was not present in any of the patients (p less than 0.01). We also found that by simply measuring fibrinogen levels by the Mancini method, we could distinguish hepatocarcinoma from cirrhosis in most cases.

Clinical significance of beta-thromboglobulin in patients with high platelet count.

The aim of the study was to investigate the relevance of beta-thromboglobulin (beta tg) measurement in patients with thrombocytosis. We have, therefore, studied the level of plasma and platelet beta tg in 74 patients with high platelet count in addition to the evaluation of platelet aggregation and platelet serotonin (5-HT) content. The determinations of platelet serotonin content and aggregation are confirmed to be useful in the differentiation between primary and secondary forms of thrombocytosis. The mean plasma level of beta tg in patients with myeloproliferative disease was significantly raised, but the amount observed in subjects with secondary thrombocytosis is increased too. Considering the amount of beta tg in relation to whole blood platelet count (beta tg ratio), no difference was observed between all patients and controls. The beta tg ratio allowed the identification of a group of patients with an increased ratio and a decreased beta tg platelet content who showed the highest occurrence of thrombosis (66%).

In vitro stability studies of a Factor IX concentrate (Bebulin).

Factor IX: C activity decay was studied in lyophilized concentrates (Bebulin, IMMUNO) stored at room temperature and in reconstituted preparations frozen and stored at -20 degrees C. A very slight, practically identical, decay of Factor IX: C was found in lyophilized concentrates kept at room temperature, in reconstituted lyophilized concentrates frozen and stored at -20 degrees C and lyophilized concentrates kept at +4 degrees C. At the end of the experiment, which was 4-5 months after the expiration date of the product, a 15-30% decay of Factor IX: C could be found in the concentrates with respect to initial levels.

Clotting changes in Cushing's syndrome: elevated factor VIII activity.

Thirteen women and 2 men affected by Cushing's syndrome were investigated. The following parameters were used: plasma and urinary cortisol levels, factor VIII assay (antigen, activity and von Willebrand factor) together with other coagulative assays. Samples were taken before surgery or before medical and/or radiation therapy and every 30-50 days after treatment and continued for 11 months. Cortisol and factor VIII were increased before treatment and decreased slowly after treatment to become normal in 3-4 months. Other clotting tests did not show any significant changes. High plasma cortisol levels seem to stimulate the production of factor VIII. Patients with Cushing's syndrome often exhibit thromboembolic complications after surgery. The clotting abnormalities responsible for such complications may be due to increased factor VIII activities.

Report of the fifth homozygous patient with factor VII Padua defect.

A new patient with factor VII Padua abnormality is presented. The propositus is a 70 old man who showed a mild bleeding tendency characterized by occasional epistaxis and a laboratory pattern of prolonged prothrombin time corrected by normal serum, normal partial thromboplastin time and normal Thrombotest. Factor VII activity was 7% using rabbit brain thromboplastin and 105% of normal using ox-brain thromboplastin. Intermediate levels were found by using thromboplastin of human origin. Factor VII cross-reacting material was normal. Parents were not consanguineous but both came from the same area. Two children of the propositus were found, as expected, to be homozygous for the abnormality. No relationship could be traced between the propositus and the other homozygous patients already reported. However, the patient came from the same geographic area, namely the Piave river valley in northeastern Italy. The discovery of the present patient, the fifth in four years, indicates that the defect might be more frequent than originally assumed.

Increased factor VIII associated activities in Cushing's syndrome: a probable hypercoagulable state.

Thirteen women and 2 men affected by Cushing's syndrome were investigated. The following parameters were used: plasma and urinary cortisol levels, factor VIII assay (antigen, activity and von Willebrand factor) together with other coagulative assays. Samples were taken before surgery or before medical and/or radiation therapy and every 30-50 days after treatment and continued for 11 months. Cortisol and factor VIII were increased before treatment and decreased slowly after treatment to become normal in 3-4 months. Other clotting tests did not show significant changes. It seems that high plasma cortisol levels may stimulate the production of factor VIII. Patients with Cushing's syndrome often exhibit thromboembolic complications after surgery. It is likely that the clotting abnormalities responsible for such complications is the increased factor VIII activities level.