Safety of hematopoietic stem cell donation in glucose 6 phosphate dehydrogenase-deficient donors.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common RBC enzymatic disorder in humans capable of producing hemolytic events. Recently, concern has been raised about using G6PD-deficienct subjects as hemopoietic stem cell (HSC) donors. In a 10-year period, 101 consecutive HSC donors were submitted to donation procedures for transplantation inside their families in our Center. All donors were tested for G6PD and 19 (19%) turned out to be G6PD-deficient. The donors' safety and the effectiveness of these transplant outcomes were compared with those of the remaining 82 donors. No difference could be observed in any safety parameter between the two groups. No difference was recorded in donors' complications rates, in HSC production, in quantity of growth factor required, in Hb early drop or in Hb recovery. No difference was found in transplant outcome. From this retrospective analysis, we conclude that a G6PD-deficient but otherwise healthy volunteer can be selected as a HSC donor.

Mycosis fungoides: disease evolution of the "lion queen" revisited.

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.

Bleeding time is prolonged during oral anticoagulant therapy.

We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular "bleeding factor".

[Activity of the coagulation and fibrinolysis in non-insulin-dependent diabetes mellitus. In vivo study]. / Attività della coagulazione e della fibrinolisi in corso di diabete mellito insulino indipendente. Uno studio in vivo.

In vivo study of blood coagulation and fibrinolysis activities in non insulin dependent diabetes mellitus. The aim of the study was to investigate in vivo blood coagulation and fibrinolysis activities in a group of diabetic patients NIDDM with and without vascular complications. For this purpose we determined two sensitive indicators in vivo of blood coagulation and fibrinolytic activities such as fibrinopeptide A and B beta 15-42 respectively. Moreover, we computed the ratio between B beta 15-42 and fibrinopeptide A in order to investigate a possible imbalance in vivo between blood coagulation and fibrinolysis. Control groups were 15 healthy subjects and 28 non diabetic patients affected by atherosclerotic disease. Fibrinopeptide A and B beta values were significantly higher in the diabetic patients than controls but there was no difference between the former group and the atherosclerotic patients. Also, no correlation was found for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose levels. There was no difference in B beta, FPA and B beta/FPAr values for patients treated with insulin and for those treated with either hypoglycemic agents or diet. Our data indicate that in diabetic patients fibrinolysis activity is increased, but it cannot counterbalance thrombin activity which appears much more enhanced. Finally, the lack of correlation for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose suggests that blood coagulation and fibronolysis abnormalities are not related to the degree of blood glucose control.

Subclinical activation of fibrinolysis in atherosclerotic disease detected by B beta 15-42 assay.

Plasma B beta 15-42 and fibrinopeptide A (FPA) concentrations, which are respectively indicators of plasmin and thrombin in vivo activity, were measured in 46 patients with ischemic arterial disease without signs of acute thrombosis. In the group as a whole, an increase in both B beta 15-42 and FPA was found. When the patients were divided in two groups on the basis of their reversible (transitory ischemic attacks and unstable angina) or irreversible (stroke and myocardial infarction) ischemic episodes, the levels of B beta 15-42 were significantly elevated only in the former group when compared to controls (p less than 0.01). In the latter group we found significantly increased levels of FPA with respect to both controls (p less than 0.01) and patients with reversible and transient ischemic episodes (p less than 0.05). Moreover, the B beta 15-42/FPA ratio was significantly lower in patients with irreversible ischemic episodes than in controls (p less than 0.01) and patients with transient ischemic episodes (p less than 0.01), while no difference was found between the latter group and controls, although FPA and B beta 15-42 were significantly higher. These results suggest that in patients with transient and reversible ischemic episodes fibrinolytic activity is able to counterbalance an increased thrombin activity, while this does not appear to occur in patients with irreversible ischemic episodes.

Thrombin activity and oral anticoagulant therapy: a preliminary study.

The aim of this work was to investigate whether the thrombin activity is related to the degree of anticoagulation induced by oral anticoagulants. Moreover, we tried to detect an optimal anticoagulation range at which the lowest possible thrombin activity can be reached. We investigated 28 patients (19 women and 9 men, mean age 54 +/- 9 years). Anticoagulation had been induced by acenocoumarol for at least 1 year before the beginning of this study. The degree of anticoagulation was monitored by the thrombotest coagulation method. The therapeutic range was 5-13%. The thrombin activity was measured by means of the fibrinopeptide A radioimmunological assay. In 15, 7, and 6 of the patients, thrombotest and fibrinopeptide A were carried out twice, once, and three times, respectively. Our results show first of all a significant positive relationship between thrombotest and fibrinopeptide A (p less than 0.001). Once this result was obtained, we tried to improve our identification of the behaviour of the thrombin activity in relation to the degree of anticoagulation assessed by thrombotest. For this purpose we employed a third-degree polynomial regression analysis which showed a better fit of the data. Since the curve became steeper from about 10% thrombotest levels, we divided the FPA values on the basis of thrombotest ranges. FPA values for the 14- to 25% thrombotest range were significantly different from those in the thrombotest range of 4-10%. Moreover, FPA levels in the 11 to 13% thrombotest range were significantly different from those in the thrombotest range of 4-10%. Our results suggest that a significant decrease in thrombin activity may be achieved only with a deep anticoagulation.

Evidence for a relationship between high fibrinogen levels and decreased thrombin activity in vivo in elderly subjects.

In order to investigate whether high fibrinogen levels were associated with elevated thrombin activity, we measured fibrinogen and fibrinopeptide A in 37 elderly healthy subjects ranging from 60 to 93 years. Fibrinogen levels (519.1 +/- 127.0 mg/dl) and fibrinopeptide A (5.9, 0.9-18.1 ng/ml) were significantly higher than in younger controls. A highly significant negative linear correlation was found between fibrinogen and fibrinopeptide A in the elderly subjects (p less than 0.01). However, a polynomial regression showed that this negative relationship was present at the fibrinogen levels ranging between 420 and 700 mg/dl. Our results suggest that high fibrinogen levels in elderly subjects do not necessarily mean that their thrombin activity is concomitantly increased.

Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment.

Plasma concentration of fibrinogen and B beta 15-42, a specific product of fibrinogen metabolism induced by plasmin, were measured in a group of patients with untreated hyperthyroidism and in controls. Significantly increased plasma levels of both parameters were observed in hyperthyroid patients. The restoration of euthyroidism either by antithyroid drug or by radioiodine caused a significant decrease of fibrinogen and B beta 15-42. These data indicate that hyperthyroidism is another clinical condition associated with increased concentration of fibrinogen and B beta 15-42.

Fibrinopeptide A and B beta 15-42 in liver cirrhosis.

In order to detect even minimal fibrinolysis activation in liver cirrhosis, we measured fibrinopeptide B beta 15-42 (B beta 15-42), an indicator of plasmin activity in vivo and alpha 2-antiplasmin (alpha 2-AP) in a group of cirrhotic patients. The second goal of this study was to investigate whether an increased fibrinolytic activity is related to a chronic disseminated intravascular coagulation. For this purpose we concomitantly measured fibrinopeptide A (FPA), marker of thrombin activity in vivo. Results show significantly higher levels of B beta 15-42 in cirrhotic patients than in control (p less than 0.01). In patients with high FPA levels we found significantly higher values than in patients with normal FPA (p less than 0.01). alpha 2-AP was lower in patients with high FPA levels than in patients with normal FPA (p less than 0.05). A significant negative correlation was found between FPA and alpha 2-AP only in patients with high FPA (p less than 0.05). There was no relationship between B beta 15-42 and FPA nor between B beta 15-42 and alpha 2-AP when all patients were considered. These findings confirm that in liver cirrhosis fibrinolysis activation may occur. The primary pathogenetic role of DIC may be important in this respect. However the lack of correlation between FPA and B beta 15-42 suggests that other pathogenetic factors may be involved in determining fibrinolysis activation.

Relationship between elevated fibrinopeptide A levels and alpha-2-antiplasmin.

In order to investigate whether alpha 2-antiplasmin (alpha 2-AP) levels may be related to thrombin activity, we measured alpha 2-AP and fibrinopeptide A (FPA) in 51 patients with clinical conditions frequently associated with increased thrombin activity. The diagnoses were: atherosclerotic disease, chronic inflammatory disease and hematological neoplastic disease. A significant negative correlation was found between alpha 2-AP and FPA (p less than 0.01). When patients were divided into three subgroups on the basis of their FPA levels, a significant reduction in alpha 2-AP was found in patients with the highest FPA concentration (greater than 9 ng/ml). Accordingly, a significant negative relationship between alpha 2-AP and FPA was found only in this subgroup (p less than 0.01). Our data suggest that the partial consumption of alpha 2-AP in patients with elevated FPA levels may reflect a subclinical fibrinolysis activation secondary to increased thrombin activity.

alpha 2 Antiplasmin and disseminated intravascular coagulation in liver cirrhosis.

Subnormal concentrations of alpha 2 Antiplasmin (alpha 2 AP) in liver cirrhosis may be due to an impaired hepatic synthesis and/or to a fibrinolysis activation in disseminated intravascular coagulation (DIC). In order to clarify this problem, in 26 cirrhotic patients (15 compensated and 11 decompensated) alpha 2 AP plasma activity and plasma Fibrinopeptide A (FPA) were measured. Serum albumin, p-Cholinesterase (p-CHE), Fibrinogen and Fibrinogen Degradation Products (FDP) were also carried out. Our data show that alpha 2 AP and FPA were equally abnormal in compensated and decompensated cirrhosis. The significant negative correlation obtained between alpha 2 AP and FPA as well as the lack of correlation between alpha 2 AP and albumin, alpha 2 AP and p-CHE in both groups suggests that, in our patients, alpha 2 AP decrease may be due to a fibrinolysis activation induced by a DIC which appears chronic since Fibrinogen and FDP were normal. These findings are in agreement with the results obtained in the four subgroups a posteriori selected on the basis of FPA levels: alpha 2 AP in subgroups with high FPA was significantly different from controls while it did not differ in subgroups with normal FPA.