Search

IF 7.702; International audience

background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN-CVT) to 87 with MPN and other venous thrombosis (group MPN-VT) and 178 with MPN and no thrombosis (group MPN-NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN-CVT and MPN-VT than in MPN-NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN-VT, MPN-CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow-up period (6.1 vs. 10.3 years, P = 0.019), a higher long-term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN-CVT than in MPN-VT group (8.8% and 4.2% patient-years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05-3.72 and 2.09, 1.09-4.00, respectively).

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.

An increased platelet number may be secondary to many conditions. Malignancies are known to induce thrombocytosis in some cases. We report data of paraneoplastic thrombocytosis recognized in 54 out of 159 patient (33.9%) with reactive thrombocytosis diagnosed in our department over the last 10 years. In most of our patients increased platelet count was observed at the time of diagnosis (33.7%) or during the first year thereafter (35.2%). Evidence of other causes for reactive thrombocytosis including iron deficiency, anemia, inflammatory diseases, surgical procedures including splenectomy, and drugs were observed in 74% of our patients. 35% of our subjects had non fatal hemorrhagic or thrombotic accidents. In about one half of our patients, increased levels of fibrinogen, ESR and plasma alpha2 globulins were observed while 5 hydroxytryptamine (5HT) intraplatelet level was normal in about all these patients. The diagnosis of paraneoplastic thrombocytosis must be postulated only after exclusion of all other reactive conditions. Often an increased platelet count in patients with cancer may be considered a reactive phenomenon.

Myocardial infarction and other arterial thrombosis are commonly maintained to be rare in hemophilia patients. This, in general, seems true but the occurrence of a thrombotic event in hemophilia B is not exceptional. A thorough search of the literature has yielded 13 patients with myocardial infarction and 1 patient with a cerebrovascular accident. There were three fatalities. In five cases MI occurred after infusion of Prothrombin Complex Concentrates. In three additional patients the event occurred after infusion of plasma, Feiba or cryoprecipitate supernatant. Four patients had an antero-lateral infarction. Two had a non-Q infarction and one each showed a multiple or a posterior-inferior form. Several therapeutic coronary procedures (GABG and PTCA) were carried out in hemophilia B patients without undue complication providing adequate level of FIX were maintained. Heparin prophilaxis was used in all patients but one. The analysis of the literature indicates that (1) MI may occur in hemophilia B patients and (2) that invasive coronary artery therapeutic procedures may be carried out without complications.

Fabris F, Luzzatto G, Soini B, Ramon R, Scandellari R, Randi ML, Girolami A (University of Padua Medical School, Padova, Italy). Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia. J Intern Med 2002; 252: 149–154. Background. As reported by major clinical series in the literature, about 2% of patients receiving unfractionated heparin (UFH) develop immune-mediated (type II) heparin-induced thrombocytopenia (HIT) that may be complicated in 30–75% of cases by a paradoxical thrombotic syndrome (HITTS), either arterial or venous. HITTS carries relevant rates of mortality and morbidity, amongst which cerebral and/or myocardial infarction and limb amputations. It is unclear as yet why some patients suffer from isolated thrombocytopenia (HIT), whilst others have HITTS. The aim of the present study was to look for clinical and laboratory features related to the occurrence of HITTS. Patients and methods. We retrospectively analysed the clinical records of 56 patients with proven HIT, as diagnosed on clinical grounds and by in vitro demonstration of immunoglobulin (IgG)/IgM against the PF4/heparin complex. Thirty-four patients (61%) had HITTS (19 venous thrombosis, seven arterial thrombosis, five arterial and venous thrombosis, two skin necrosis, one diffuse intravascular coagulation), whereas 22 had uncomplicated HIT. Amongst HITTS patients, two had limb amputation, five had recurrent thrombosis and seven died. Amongst HIT patients three died from causes unrelated to HIT. Results. No significant difference in sex, age, previous exposure to heparin, UFH route of administration or dose, duration of therapy, time of onset of thrombocytopenia and platelet count recovery, nor antiheparin/PF4 antibodies subtype (IgG or IgM) was detected when comparing HIT and HITTS. In contrast, in the HITTS group a higher prevalence of orthopaedic surgery (15 of 34 vs. 2/22; P=0.01), a significantly lower platelet count nadir (43 ± 32 vs. 75 ± 63 × 109/L; P=0.01) and a significantly higher titre of antiheparin/PF4 antibodies, expressed as optical density of enzyme-linked immunosorbent assay (ELISA); (1989 ± 1024 vs. 1277 ± 858; P=0.009), were observed in comparison with the HIT group. Amongst HITTS patients, the prevalence of venous thrombosis was significantly higher in orthopaedic patients and in those being treated for venous thromboembolism (18/24 vs. 1/9 patients, χ2 8.4, P=0.004), whilst arterial thrombosis (ART) occurred more often in heparin treatment for arterial disease (3/4 vs. 4/29 patients, χ2 4.6, P=0.03). Conclusions. Orthopaedic surgery, the severity of thrombocytopenia and high antiheparin/PF4 antibodies titre are adverse prognostic or concurrent factors in the development of HITTS.

Reactive thrombocytosis due to malignancies and in particular those related to lymphomas have not yet been extensively evaluated. We report data on thrombocytosis recognized in 18 out of 101 patients with lymphomas diagnosed in our department over the last 3 years. All showed high platelet counts at the time of diagnosis. The incidence of thrombocytosis seems to be more frequent in males (21.2%) than in females (14.8%) and a slightly higher frequency was found in Hodgkin's disease (21.4%) than in non Hodgkin's lymphomas (16.4%). The incidence of thrombocytosis in lymphomas seems to be similar to that seen in other malignancies and because of this we conclude that a high platelet count cannot be used to distinguish malignancies.

We report the case of a relatively young man with multiple and fatal thrombosis associated with essential thrombocythaemia. The clinical and laboratory examinations performed before his death were in agreement with the diagnostic criteria proposed by PVSG. The autopsy revealed myocardial infarction and pulmonary embolisms. This case suggests that young patients with primary thrombocytosis should be treated with antiplatelet agents in spite of the absence of other thrombotic risks.

2 members of a family, a child and his father, showed a combined morphological abnormality of leukocytes and platelets. The abnormality consisted of the presence of pseudodrumsticks in the neutrophils and of large platelets. One or more than one pseudodrumstick was present in about 40% of neutrophils. Leukocyte count, differential count and enzymatic stains were normal. Large platelets constituted about 25% of the platelet population. 1 patient also had mild thrombocytopenia which appeared to be unrelated to the basic defect since it appeared after a parotitis infection. Platelet function was normal but for a moderate prolongation of the bleeding time in the patient who had mild thrombocytopenia. No chromosomal abnormality was present in the propositi. The condition seems different from other leukocyte and platelet abnormalities so far described.

We performed a retrospective study on 21 patients, aged 70 years or more, affected by polycythemia vera (PV) or essential thrombocythemia (ET). As controls, we evaluated 10 younger ET patients. The results indicate that in older ET subjects there was a lower incidence of hemorrhagic and thrombotic complications than in younger patients and PV patients. However, platelet number and platelet function tests were similar in all the patients studied. We suppose that an increase in hematocrit as seen in PV is much more dangerous as compared to an isolated increase in platelet count, and that thrombocytosis alone in old age can be an isolated expression of a natural involution of blood marrow similar to myelofibrosis.

Bartter’s syndrome is characterized by hypokalemia, hyperreninemia, hyperaldosteronism without hypertension, and juxtaglomerular cell hyperplasia.1 Recent studies have demonstrated an increase of the urinary excretion of prostaglandins (PGs) PGE2, PGF2α 2–4 and 6-keto PGF1α 5,6 in cases of Bartter’s syndrome.

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%).

The effect of Sulphinpyrazone on the anticoagulant response to Warfarin was evaluated by a double-blind study in 11 patients with prosthetic heart valves. Six patients received Warfarin and Sulphinpyrazone and 5 Warfarin and placebo. Sulphinpyrazone potentiated the anticoagulant effect of Warfarin. Patients receiving Sulphinpyrazone needed about half the amount of Warfarin as compared to the control group. There were four bleeding episodes in the Sulphinpyrazone group and one episode in the control group. It was difficult to regulate the dose of Warfarin in patients also receiving Sulphinpyrazone.

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L. Fil: Noris, Patrizia. Istituti di Ricovero e Cura a Carattere Scientifico. Policlinico San Matteo di Pavia; Italia. Università degli Studi di Pavia; Italia Fil: Schlegel, Nicole. Université Paris Diderot - Paris 7; Francia Fil: Klersy, Catherine. Istituti di Ricovero e Cura a Carattere Scientifico. Policlinico San Matteo di Pavia; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Civaschi, Elisa. Università degli Studi di Pavia; Italia Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Favier, Remi. Inserm; Francia. Armand Trousseau Children’s Hospital; Francia. French Reference Center for Inherited Platelet disorders; Francia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Latger Cannard, Véronique. Centre Hospitalo-Universitaire. Service d’Hématologie Biologique; Francia. Reference French Centre. Centre de Compétence Nord-Est des Pathologies Plaquettaires; Francia Fil: Cuker, Adam. University of Pennsylvania; Estados Unidos Fil: Nurden, Paquita. Hôpital Xavier Arnozan; Francia Fil: Greinacher, Andreas. Institut für Immunologie und Transfusionsmedizin; Alemania Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia Fil: Pecci, Alessandro. Università degli Studi di Pavia; Italia Fil: Hurtaud Roux, Marie Françoise. Université Paris Diderot - Paris 7; Francia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Muñiz Diaz, Eduardo. Banc de Sang i Teixits de Catalunya. Immunohematology Department; España Fil: Randi, Maria Luigia. Università di Padova; Italia Fil: Trillot, Nathalie. Centre Hospitalier Régional Universitaire de Lille. Pôle Biologie Pathologie Génétique. Institut d’Hématologie-Transfusion; Francia Fil: Bury, Loredana. Università di Perugia; Italia Fil: Lecompte, Thomas. Hôpitaux Universitaires de Genève; Suiza. Université de Genève. Faculté de Médecine; Suiza Fil: Marconi, Caterina. Università di Bologna; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia Fil: Balduini, Carlo L.. Istituti di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Pavia; Italia Fil: European Hematology Association Scientific Working Group on Thrombocytopenias and Platelet Function Disorders. No especifica