The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease.

B-cell prolymphocytic leukemia: a specific subgroup of mantle cell lymphoma.

B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell malignancy that may be hard to distinguish from mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). B-PLL cases with a t(11;14) were redefined as MCL in the World Health Organization 2008 classification. We evaluated 13 B-PLL patients [7 being t(11;14)-positive (B-PLL+) and 6 negative (B-PLL-)] and compared them with MCL and CLL patients.

Cardiopulmonary imaging, functional and laboratory studies in sickle cell disease associated pulmonary hypertension.

Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high-resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of > or =2.

PFA-100 monitoring of von Willebrand factor (VWF) responses to desmopressin (DDAVP) and factor VIII/VWF concentrate substitution in von Willebrand disease type 1 and 2.

Dose-response relationship was studied between PFA-100 closure times (PFA CTs) and factor (F)VIII-von Willebrand factor (VWF) parameters in patients with von Willebrand disease (VWD) type 1 and type 2 before and after treatment with DDAVP (n=84) or FVIII/VWF concentrate (n=38). DDAVP treatment of patients with VWD type 1 normalised the PFA CTs by increasing VWF levels to normal. Of the 14 patients with VWD type 2, PFA CTs did not normalize in eight.

Large and medium-sized pulmonary artery obstruction does not play a role of primary importance in the etiology of sickle-cell disease-associated pulmonary hypertension.

Background: Pulmonary hypertension (PHT) occurs in approximately 30% of adult patients with sickle-cell disease (SCD) and is a risk factor for early death. The potential role of pulmonary artery obstruction, whether due to emboli or in situ thrombosis, in the etiology of SCD-related PHT is unknown.

Methods: Consecutive SCD patients were screened for PHT (defined as a tricuspid regurgitant jet flow velocity > or = 2.

An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura.

Abstract The objective of this open label, phase 1-2, multicentre trial was to evaluate the safety of AMG 531, a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura. Four patients were assigned to each of four unit-dose cohorts: 30, 100, 300 or 500 microg, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 x 10(9)/l). Safety was assessed by adverse event (AE) monitoring, clinical laboratory studies and antibody assays.

Splenectomy for the treatment of thrombotic thrombocytopenic purpura.

Plasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these conditions but its value remains controversial.

[A patient with sinus thrombosis associated with paroxysmal nocturnal hemoglobinuria].

A 27-year-old woman with a history of aplastic anaemia complained of poor control of her right arm and hand, unsteady gait, and headache that increased while in a recumbent position. She was diagnosed with cerebral sinus thrombosis. Additional investigation revealed paroxysmal nocturnal haemoglobinuria (PNH).

A new polyadenylation site mutation associated with a mild beta-thalassemia phenotype.

At least 180,000 autochthonous and allochthonous people are carriers of a large spectrum of hemoglobinopathies in The Netherlands. We describe two cases, the first, a 33-year old Surinamese Creole woman, studied because of an intermediate hemolytic anemia; the second, a couple requesting analysis because of a previously diagnosed carrier state in the male partner, while the carrier state in the pregnant female was uncertain.

[Activity loss of Von Willebrand factor cleaving protein (ADAMTS-13) is diagnostic for primary and pregnancy-related thrombotic thrombocytopenic purpura].

Objective: To determine whether the measurement of the Von Willebrand factor cleaving protease ADAMTS-13, such as is carried out at the University Medical Centre of Utrecht, The Netherlands, contributes towards the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura (TTP).

Design: Descriptive.

Method: In a group of 98 patients from 21 hospitals, with a Coombs-negative haemolytic anaemia and thrombocytopenia, the ADAMTS-13 activity was measured.

In vitro studies, pharmacokinetic studies and clinical use of a high purity double virus inactivated FVIII/VWF concentrate (Immunate) in the treatment of von Willebrand disease.

Patients with type 2 and 3 von Willebrand disease (VWD) are treated with factor VIII/VWF concentrate in case of bleeding or surgery. Immunate (Baxter, Vienna, Austria) is a double virus inactivated FVIII/VWF concentrate and is registered in several countries for patients with VWD with reduced FVIII levels. We performed an in vitro, a pharmacokinetic and a clinical study to evaluate Immunate in VWD.

Effective and safe use of recombinant factor VIIa (NovoSeven) in elderly mild haemophilia A patients with high-titre antibodies against factor VIII.

Three patients with mild haemophilia A who developed high-titre antibodies against factor VIII at high age are reported. These patients had only a limited number of exposure days of FVIII concentrates in the past. The patients had to undergo surgery or presented with recurrent bleeding episodes.

Hematological long-term results of laparoscopic splenectomy for patients with idiopathic thrombocytopenic purpura: a case control study.

Background: Laparoscopic splenectomy (LS) for idiopathic thrombocytopenic purpura (ITP) appears, when compared to open splenectomy (OS), associated with immediate important advantages. However, in a number of patients splenectomy does not lead to an adequate response, or after initial adequate response a relapse occurs after some time. A relapse may be associated to the presence of accessory spleens and splenosis.

The value of alloantibody detection in predicting response to HLA-matched platelet transfusions.

Alloantibody tests demonstrate immunological causes of insufficient increments in random platelet transfusions. The value of a positive or negative test result in predicting the outcome of human leucocyte antigen (HLA)-matched transfusions in patients refractory to leucodepleted random platelet transfusions has not been assessed. We retrospectively evaluated the outcome of the first HLA-matched platelet transfusion in 72 patients with haematological diseases in two ways: first, the strategy according to which the patient was selected for HLA-matched platelet transfusions was analysed.

A novel 7.9 kb deletion causing alpha+-thalassaemia in two independent families of Indian origin.

We describe the characterization of a novel 7.9 kb deletion that eliminated one of the duplicated alpha-globin genes, causing an alpha+-thalassaemia phenotype in two independent carriers of Suriname-Indian origin. The molecular characterization of the deletion breakpoint fragment revealed neither involvement of Alu repeat sequences nor the presence of homologous regions prone to recombination, suggesting a non-homologous recombination event.

Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial.

A nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process. A total of 103 patients received one or more transfusions of either PCT test (311 transfusions) or conventional reference (256 transfusions) pooled, leukoreduced platelet components stored for up to 5 days before transfusion.

[Intermittent thrombocytopenia as a manifestation of Von Willebrand's disease].

A 38-year-old man with Von Willebrand's disease type 2 came to us for treatment advice in relation to a trip abroad, and also a 53-year-old woman with bleeding treated as idiopathic thrombocytopenic purpura (ITP). In the man, a trial dose of desmopressin led to severe thrombopenia, and in the woman, treatments, such as splenectomy and prednisone in the past, had been ineffective. In both patients further investigations led to the diagnosis 'Von Willebrand-disease type 2B'.

Serum thrombopoietin levels in relation to disease status in patients with immune thrombocytopenic purpura.

Pre- and post-treatment serum thrombopoietin (TPO) concentration was measured in 35 patients with immune thrombocytopenic purpura (ITP). Mean post-treatment levels were significantly lower (P = 0.02) than pretreatment and not different for treatment modality.

Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.

Patients with chronic immune thrombocytopenic purpura (ITP) who are unresponsive to corticosteroids require splenectomy, but if this fails, treatment is difficult. We tried to induce durable remissions in ITP patients refractory to corticosteroids before or after splenectomy by applying strong immunosuppression with the combination of cyclosporin A (CyA 5 mg/kg/d) and prednisone (0.4 mg/kg/d).

Hypercoagulability states in upper-extremity deep venous thrombosis.

Deep venous thrombosis of the upper extremity (DVTUE) is a rare thrombotic disorder that may occur spontaneously but is most often related to predisposing factors, such as an indwelling central venous catheter, malignancy, or exercise. The role of coagulation disorders, i.e.

[Deep venous thrombosis of the arm: etiology, diagnosis and treatment].

Thrombosis of the upper extremity is frequently (30-52%) related to the use of an indwelling venous catheter, but it can also occur in healthy individuals after exercise. In the past it was considered a relatively benign thrombotic event, which was treated conservatively, sometimes even without anticoagulant therapy. Recent studies have shown that complications of deep venous thrombosis of the upper extremity occur frequently: pulmonary embolism (8-36%), recurrence thrombosis after cessation of anticoagulant treatment (2-15%) and post-thrombotic syndrome (up to 50%).