Arturo Cafolla

Thrombophilic screening in young patients (< 40 years) with idiopathic ischemic stroke: a controlled study.

INTRODUCTION Despite extensive clinical and laboratory investigations, the etiology of ischemic stroke remains unknown in approximately one third of patients. MATERIALS AND METHODS Thirty-four consecutive patients less than 40 years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented ischemic stroke underwent, one year after the acute event, laboratory evaluation of antithrombin, protein C, free and total protein S, activated protein C resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR) were also evaluated and compared to the results obtained in 120 normal controls. RESULTS Antithrombin and protein C levels resulted normal in all cases. One patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had activated protein C resistance. Homocysteine levels above 15 μmol/L were found in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of 120 (1.66%) controls (OR=95.31; 95% C.I.: 18.22-667.81). The multivariate analysis selected that the presence of APA was significantly associated with an increased risk of stroke (OR=156.60; 95% C.I.: 25.99-943.47) in this cohort of patients. The combination between APA and cardiovascular risk factors determined a risk of 29-fold (OR=29.31; 95% CI: 3.28-261.69). DISCUSSION Our data suggest that the presence of APA is associated with an increased risk of idiopathic ischemic stroke in young patients. Furthermore, also the combination of APA and cardiovascular risk factors is significantly associated with development of idiopathic ischemic stroke.

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.

Hereditary protein C deficiency and thrombosis risk: Genotype and phenotype relation in a large Italian family

Protein C (PC) deficiency is an autosomal dominant inherited disorder associated with spontaneous and recurrent thrombotic events. Factor V Leiden (FVL) increases the risk of thrombosis in PC‐deficient type I families. We have investigated the relationship between PC deficiency genotype and clinical phenotype in a large four‐degree Italian family followed since 1988. Methods: PC activity and antigen levels were quantified; sequencing of PC DNA was performed to identify polymorphism. FVL and factor II (G20210A) polymorphism were screened. Results: PC activity ranged from 5% to 9%, and PC antigen levels were 5,3% in two homozygous for PROC missense mutation Arg32Cys; PC activity ranged from 18% to 60% and antigen levels from 21% to 64%, respectively, in 11 heterozygous for Arg32Cys; PC activity was 99% and 120% in two wild type. Of 15, eight were heterozygous for FVL. The two subjects with PC < 6%, homozygous for Arg32Cys and heterozygous for FVL, suffered from thrombosis during childhood. Of 11, six subjects with PC deficiency and heterozygous for FVL showed the first thrombosis at an age between 21 and 54. None of the five PC‐deficient subjects, who were wild type for FVL, showed thrombosis. Two subjects with PC > 70%, both heterozygous for FVL developed thrombosis in the presence of another risk factor. This study suggests that FVL and PROC mutations increase the risk of thrombosis in subjects with PC deficiency, which could be considered as a ‘variable’ risk factor. The thrombosis‐prone PC‐deficient families carry additional risk factors for thrombosis.

Oral anticoagulant therapy in Italian patients 80 yr of age or older with atrial fibrillation: a pilot study of low vs. standard PT/INR targets.

Oral anticoagulation therapy (OAT), which aims to prevent thromboembolism in patients with atrial fibrillation (AF), is underused in subjects who are over the age of 80 yr because of the associated bleeding risk. The aim of this study was to evaluate the efficacy and safety of OAT with low (2.0) vs. standard (2.5) PT/international normalised ratio (INR) targets in patients over the age of 80.

The effectiveness of a new method using an extra-alveolar hemostatic agent after dental extractions in older patients on oral anticoagulation treatment: an intrapatient study

OBJECTIVE The present study aimed to evaluate the effectiveness of a new adhesive agent, HemCon Dental Dressing (HDD), in patients receiving oral anticoagulant treatment (OAT), who were undergoing nonsurgical tooth extractions without interruption or reduction of OAT, compared with that of a common local hemostatic agent. STUDY DESIGN Twenty patients on OAT with an international normalized ratio (INR) ranging between 1.6 and 3.5 were recruited. In the same session, each patient was subjected to the extraction of two teeth: In the test site the HDD was applied, and in the control site, a common hemostatic sponge (CollaPlug, Zimmer Dental) was used. RESULTS The mean application time was significantly lower in the test group than in the control group, and this difference is statistically significant. The mean postoperative pain was significantly lower in the test group than in the control group the morning after surgery and at the time of suture removal. Post-extraction socket healing was significantly better in the test group than in the control group. CONCLUSIONS Tooth extraction in patients receiving OAT and have an INR lower than 3.5 is a safe procedure without discontinuation of the OA regimen. The HDD seems to reduce postoperative side effects and obtain rapid soft tissue healing.

Red cell folate in elderly patients with myelodysplastic syndrome

Abstract: During a 7‐month period a prospective study of 71 anaemic patients (29 males and 42 females) over the age of 50 was undertaken in order to identify patients with myelodysplastic syndrome (MDS). The mean values of mean corpuscular volume (MCV), serum ferritin, folate, vitamin B12 and red cell folate (RCF) of patients grouped according to the diagnosis were compared to those observed in age‐matched blood donors. Forty‐four of the 71 elderly patients showed macrocytic anaemia: 21 of them had gastric disease and the remaining 23 MDS. Two further patients with MDS showed microcytic anaemia. The 25 patients diagnosed with MDS were subclassified according to the FAB nomenclature: 9 had a refractory anaemia with excess of blasts and 16 refractory anaemia. The mean values of MCV, serum folate, ferritin, vitamin B12 and RCF were statistically different between patients with macrocytic anaemia due to gastric disease and patients with MDS. Among patients with MDS, the RCF level pathologically high was inversely correlated to the haemoglobin level (r=‐0.39; p<0.05). Thus the RCF and serum folate may represent useful parameters for the diagnosis of MDS in elderly anaemic patients.

The Use of a Chitosan-Derived Hemostatic Agent for Postextraction Bleeding Control in Patients on Antiplatelet Treatment

PURPOSE The current approach for tooth extraction in patients receiving antiplatelet treatment requires the use of local hemostatic agents without previous thromboembolic treatment interruption. The aim of the present study was to evaluate the effectiveness of an extra-alveolar hemostatic agent, the HemCon Dental Dressing (HDD), in controlling postsurgical bleeding. MATERIALS AND METHODS Routine, atraumatic tooth extractions were performed in a single session under local anesthesia without a vasoconstrictor and without interruption of antiplatelet therapy. All patients underwent extraction of 2 teeth in the same session, with each in a different dental hemi-arch, and the hemostatic method to be used was randomly chosen: in the test site, the HDD was applied, whereas in the control site, a common hemostatic sponge (CollaPlug, Zimmer Dental) was applied and stabilized in situ with a suture. For each surgery, 2 different times were measured: the time required for hemostatic agent application and the time required for hemostasis achievement. Postoperative pain and healing quality also were evaluated. RESULTS Twenty outpatients were enrolled. The mean application time was considerably shorter in the test group than in the control group; the mean bleeding time in the control group was considerably shorter than in the test group; pain values were lower in the test group than in the control group, especially at suture removal; and postextraction socket healing was better in the test group than in the control group. CONCLUSION HDD seems to be a valid and safe alternative in treating postextraction sockets in outpatients under single-drug antiplatelet treatment in the absence of surgical wound lacerations.

Anticoagulant therapy with fondaparinux in a liver transplant patient with thrombosis and liver fibrosis: a case report

The treatment with fondaparinux is the effective and safe anticoagulant therapy in liver transplant patient on immunosuppressive therapy with arterial thrombosis, and it seems able to reduce liver fibrosis. Although this treatment is not generalizable, further prospective large studies need to confirm this case report.

Inherited thrombophilia in patients with thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare, but lifethreatening disorder, characterized by thrombi in the microvasculature, resulting in vascular occlusions that lead to tissue ischemia and end-organ injury [1]. The presenting triad of microangiopathic hemolytic anemia, thrombocytopenia and neurologic symptoms is found in themajority of patients, while the pentad including fever and renal involvement is present in 40% of the patients. A severe deficiency of ADAMTS13, caused by a genetic mutation or inhibitory autoantibodies, is considered the underlying pathophysiological mechanism [2]. Although the incidence of prothrombotic polymorphisms in TTP patients has been explored [3–5,8], data reported so far are contradictory. Raife et al. [4] suggested that factor V Leiden could be a pathogenetic risk factor in TTP patients with normal ADAMTS13 activity. Krieg and coworkers [5] did not find a significantly different factor V Leiden prevalence in patients with normal ADAMTS13 activity compared to patients with severe ADAMTS13 deficiency. Based on these findings, we retrospectively evaluated thrombotic risk factors in 32 TTP patients during the remission phase of their disease.

Folate status and homocysteine level in Italian patients aged under 60 on oral anticoagulant therapy

BACKGROUND. Folate deficiency occurs frequently and the related hyper-homocysteinaemia is considered a risk factor for thrombosis. We investigated folate status and homocysteine (Hcy) concentration in patients under 60 years on oral anticoagulant therapy (OAT) for previous venous or arterial thrombosis and in healthy blood donors. PATIENTS AND METHOD. Thirty-nine patients (mean age 35.2 years) on OAT for longer than 6 months and forty 44 healthy blood donors (mean age 36.0 years) were evaluated. Diet, serum folate (SF), red blood cell folate (RCF), homocysteinaemia, vitamin B12 levels and the mutation C677T of methylenetetrahydrofolate-reductase (MTHFR) gene were determined. RESULTS. The mean SF and Hcy concentrations were significantly higher in patients compared with blood donors (SF r = r 17.7 versus 10.5 r nmol/L, P r < r 0.0001; Hcy r = r 11.7 versus 8.9 r 7 mol/L, P r = r 0.009). Twelve out of 39 patients and 7 out of 44 blood donors were homozygous for the mutation C677T of MTHFR gene. Among the remaining subjects, non-homozygous for the mutation, the patients (27) had mean SF and Hcy levels significantly higher than the (37) blood donors (SF r = r 18.1 versus 10.8 r nmol/L, P r < r 0.0001; Hcy r = r 10.3 versus 7.9 r 7 mol/L, P r < r 0.0006). CONCLUSION. Italian patients aged under 60 years on OAT and non-homozygous for the mutation C677T of MTHFR gene, had SF and Hcy concentrations significantly higher than the control group.