Mariangela Fadin

Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events

The role of circulating microparticles (MP) of different origin and tissue factor (TF)-bearing in overweight and obese patients with and without metabolic syndrome is still a matter of debate. In a case-control study, the presence of hypercoagulability was evaluated in overweight and obese patients by measuring MP, thrombin generation (TG) and FVIIa-AT complexes. Twenty overweight patients (body mass index [BMI] range 25-29.9 kg/m²), 20 with I degree (30-34.9 kg/m²), 20 with II degree (35-39.9 kg/m²) and 20 with III degree obesity (≥ 40 kg/m²) were enrolled and compared to 40 age and gender-matched normal weight individuals. A significant increase in median levels of all MP subtypes was observed in the three degrees of obese patients compared to controls. Overweight patients had higher levels of annexin V-MP (AMP), endothelial-derived, leukocyte-derived and TF-bearing MP than controls. Obese patients had a significantly shorter median lag time (p< 0.05), higher median peak thrombin (p< 0.01) and increased median endogenous thrombin potential [ETP] (p< 0.001) compared to controls. Overweight subjects had significantly increased ETP compared to controls (p< 0.05). Both AMP levels and ETP were found to positively correlate with BMI, waist circumference, and inflammatory parameters. No significant increase in FVIIa-AT complex was seen in cases compared to controls. We conclude that obesity is associated with overproduction of procoagulant MP and increase TG. Interestingly, hypercoagulability is found in overweight patients free of metabolic syndrome and increases with the severity of obesity. Assessment of MP and TG may be helpful in the early characterisation of the prothrombotic state in obese patients.

Alterations in the coagulation profile in renal pig-to-monkey xenotransplantation.

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this 
 model.

Prevalence of Antiphospholipid Antibodies and Lupus Anticoagulant in Juvenile Patients with Objectively Documented Deep-vein Thrombosis

The prevalence of lupus anticoagulant (LA) and antiphospholipid antibodies (APA) in young patients (<45 years) with deep-vein thrombosis (DVT) is not clearly defined yet. We studied 93 consecutive patients (36 males, 57 females; aged 15 to 45) with objectively documented DVT. A control group consisting of 100 nor mal, sex- and age-matched individuals was also investi gated. In all subjects, we evaluated prothrombin time (PT), partial thromboplastin time (PTT), AT III antigen and activity, protein C antigen and activity, free and total protein S antigen and protein S activity, fibrinogen, plas minogen, heparin cofactor II, plasminogen activator in hibitor (PAI), lupus anticoagulant (LA), and APA. For the assessment of LA, we used the PTT-LA kit (Boeh ringer Mannheim, Milan, Italy) as a screening test, with mixing studies with the Staclot-PNP kit and the Staclot- LA kit (Boehringer Mannheim, Milan, Italy) as confirma tory procedures. For the detection of APA, we used a commercially available enzyme-linked immunoassay (ELISA) (Asserachrom APA, Boehringer Mannheim, Mi lan, Italy). History was elicited in all patients to deter mine if the thrombotic episode was idiopathic or the re sult of a well-identified risk factor. LA was found in 11 (11.8%) patients. APA were positive in 13 (14%) and bor derline in 19 (20.4%) patients. In the control group, no patients were positive for LA or APA, but five exhibited borderline APA levels. LA was significantly more fre quent (p = 0.05) in patients with idiopathic DVT than in patients with secondary DVT; no difference was found for APA (p > 0.5). An inherited coagulation defect was found in seven (7.5%) patients. Our data suggest that the presence of LA or APA is associated with an increased incidence of thrombotic manifestation in young patients. Moreover LA is more frequent in patients with idiopathic DVT. Because the incidence of recurrent thrombotic manifestations in patients with LA or APA is estimated to be ∼50% within 2 years from the first thrombotic episode, the tests should be performed in all patients with juvenile thrombosis.

The effect of pre-eclampsia on the levels of coagulation and fibrinolysis factors in umbilical cord blood of newborns.

The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 ± 0.92 versus 2.88 ± 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 ± 46.97 versus 156.08 ± 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.

Combined factor V and factor VII deficiency due to an independent segregation of the two defects.

A patient with combined factor V and factor VII deficiency is described together with a family study. The pro positus appeared to be double heterozygous for factor V and factor VII deficiency. Since the patient showed a parallel de crease of activity and antigen, he appeared to be double het erozygous for a true deficiency. The patient had inherited the factor V defect from the mother and the factor VII defect from the father. The parents of the propositus were not consanguin eous. Other family members were found to have isolated factor V or factor VII deficiency. This is the third family so far described with this peculiar combined defect but the first to be investigated by clotting and immunologic assays.

Potential Role of Thrombelastography in the Monitoring of Acquired Factor VIII Inhibitor Hemophilia A: Report on a 78-year-old Woman With Life-threatening Bleedings:

A 78-year-old woman was admitted to our hospital because of syncope associated with hematomas in both legs. Acquired hemophilia A (AHA) with a low antifactor VIII antibodies activity was diagnosed. Whole blood (WB) thrombelastographic profile depicted a hypocoagulable state. During hospitalization, the patient experienced life-threatening bleedings in the neck and in the right thigh. FVIII concentrates and rFVIIa was safe and effective in controlling acute hemorrhagic symptoms. Immunosuppressive therapy was used successfully to eradicate the inhibitor. At discharge, FVIII inhibitor was absent and thrombelastogram showed a normal profile. Our report confirms that AHA is a heterogeneous condition in terms of risk of bleeding. Even though the criteria for the diagnosis of AHA is quite well defined, a laboratory test useful to predict the bleeding risk and monitor the response to treatment is lacking. ROTEM profile appears to be correlated with the response to treatment and with the eradication of the inhibitor.

Identification of a novel frameshift mutation causing a premature stop codon in a young Nigerian man with type I antithrombin deficiency

Antithrombin (AT) is the main physiological inhibitor of thrombin and other proteases of the coagulation system [1]. Inherited AT deficiency is an autosomal dominant disorder that predisposes to recurrent venous thromboembolism (VTE) [2]. The deficiency is caused by mutations in the gene encoding AT (SERPINC1) [3]. Genetic lesions leading to inherited thrombophilia and VTE in black populations have rarely been reported. Here, we identified a novel frameshift mutation responsible for inherited AT deficiency in a black African man who presented with recurrent deep vein thrombosis (DVT).

Uneventful coronary artery bypass surgery without prophylactic replacement therapy in a patient with a novel heterozygous FVII gene deletion

proximal articular surface (above the femorotibial joint for knees and above the tibiotalar joint for ankles), L2 for joint space, L3 for distal articular surface (below the femorotibial joint for knees and below the tibiotalar joint for ankles); Fig. 1a,b], as well as for annotation. The annotations may be abbreviated as SAG, AX, ANT (sagittal, axial, anterior) as shown in the footnotes of Table 1. Although the sagittal images are away from the median plane and are in fact oblique-sagittal, for ease of understanding, the term SAG should be used (Figs 2 and 3). The scanning sequence may be such that all anterior scans are performed before proceeding to the posterior scans, to avoid multiple changes in patient position. The true lateral and true medial (coronal) planes were found not to be contributory in ankles as they overlie the malleoli and hence can be excluded from the protocol. With regard to colour Doppler imaging, we defined the planes that best capture the vascularity of perisynovial tissues in the protocol (Table 1). We believe that by standardizing and simplifying the planes and landmarks for acquisition of this sonographic protocol in haemophilic knees and ankles, the ultrasound modality may become more user-friendly in this field, reducing inter-operator variability of data acquisition and facilitating the conduct of future clinical trials. Our expectation is that the proposed protocol can be applied to the assessment of haemophilic joints of patients with different levels of severity of arthropathy, both in research and clinical practice.