Antithrombotic Treatment in Patients With Hemophilia: an EHA-ISTH-EAHAD-ESO Clinical Practice Guidance

Cardiovascular disease is an emerging medical issue in patients with hemophilia (PWH) and its prevalence is increasing up to 15% in PWH in the United States. Atrial fibrillation, acute and chronic coronary syndromes, venous thromboembolism, and cerebral thrombosis are frequent thrombotic or prothrombotic situations, which require a careful approach to fine-tune the delicate balance between thrombosis and hemostasis in PWH when using both procoagulant and anticoagulant treatments. Generally, PWH could be considered as being naturally anticoagulated when clotting factors are 20 IU/dL in need for any form of antithrombotic therapy, usually treatment without additional clotting factor prophylaxis could be used, but careful monitoring for bleeding is recommended. For antiplatelet treatment, this threshold could be lower with single-antiplatelet agent, but again factor level should be at least 20 IU/dL for dual antiplatelet treatment. In this complex growing scenario, the European Hematology Association in collaboration with the International Society on Thrombosis and Haemostasis, the European Association for Hemophilia and Allied Disorders, the European Stroke Organization, and a representative of the European Society of Cardiology Working Group on Thrombosis has produced this current guidance document to provide clinical practice recommendations for health care providers who care for PWH

Antithrombotic Treatment in Patients With Hemophilia: an EHA-ISTH-EAHAD-ESO Clinical Practice Guidance

Cardiovascular disease is an emerging medical issue in patients with hemophilia (PWH) and its prevalence is increasing up to 15% in PWH in the United States. Atrial fibrillation, acute and chronic coronary syndromes, venous thromboembolism, and cerebral thrombosis are frequent thrombotic or prothrombotic situations, which require a careful approach to fine-tune the delicate balance between thrombosis and hemostasis in PWH when using both procoagulant and anticoagulant treatments. Generally, PWH could be considered as being naturally anticoagulated when clotting factors are 20 IU/dL in need for any form of antithrombotic therapy, usually treatment without additional clotting factor prophylaxis could be used, but careful monitoring for bleeding is recommended. For antiplatelet treatment, this threshold could be lower with single-antiplatelet agent, but again factor level should be at least 20 IU/dL for dual antiplatelet treatment. In this complex growing scenario, the European Hematology Association in collaboration with the International Society on Thrombosis and Haemostasis, the European Association for Hemophilia and Allied Disorders, the European Stroke Organization, and a representative of the European Society of Cardiology Working Group on Thrombosis has produced this current guidance document to provide clinical practice recommendations for health care providers who care for PWH

Validation of a modified cryopreservation method for leukemic blasts for flow cytometry assessment

BACKGROUND: Cryopreservation, a common method for storing human cells, has advantages when cells are used in retrospective studies of selected cell populations. Frozen lymphocytes can be used for tissue typing, for monitoring cell-mediated immunity, and for various immunological tests. Our report describes an efficient, simple and inexpensive method for cryopreservation of human acute leukemia cells. METHODS: Leukemia cells from 20 newly diagnosed cases were frozen at -80°C after cryopreservation with 5% dimethysulfoxide and then assayed by flow cytometry for antigen expression determined by monoclonal antibodies at different time intervals. RESULTS: All cases had viability above 75% at presentation. After 4 weeks, 91% of pre-B ALL, 88% of T-ALL, 100% of AML, and 100% of biphenotypic aliquots had viability over 75%. Viability continued to be reliably above 75% at 6 weeks from cryopreservation. CONCLUSION: We confirm that the method does not significantly alter the viability of cells and it preserved the antigenic expression of leukemia cells

Hairy-plasma cell leukemia

Plasma cell leukemia (PCL) is defined by the presence of more than 2 × 109/L PCs in the peripheral blood. It is a very rare type of leukemia with poor outcome. In this case, we report a PCL case with peripheral blood morphology of hairy cell leukemia. We describe the clinical and pathological presentation of a 44-year-old woman who found to have peripheral abnormal hairy lymphoid looking cells confirmed to be lambda specific plasma leukemic cells by flow cytometry. Eventually, this patient managed with autologous stem cell transplantation after conformation of such rare diagnosis and five cycles of VCD regimen “Bortezomib, Cyclophosphamide, and Dexamethasone” based chemotherapy regimen and showed a good response so far

Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia

Patients with chronic myeloid leukemia (CML) infrequently present in blast crisis (BC). While most BC are of myeloid origin, megakaryocytic BC is rare, especially at the time of CML diagnosis. We describe the first pediatric patient presenting with megakaryocytic leukemia and having BCR-ABL1 translocation as the single chromosomal abnormality. Clinical features were more suggestive of CML in megakaryocytic blast crisis than Philadelphia chromosome positive de novo AML. The patient was treated with AML-directed chemotherapy and imatinib mesylate followed by umbilical cord blood stem cell transplantation. The patient was in complete molecular response 16 months after stem cell transplantation

Thrombin generation and endothelial dysfunctional markers in different stages of nephrotic syndrome

Objectives: Venous thromboembolism is an important and potentially life-threatening complication of nephrotic syndrome (NS). This study aims to evaluate the functional test of thrombin generation (TG) in different stages of NS; determine its relation with the coagulation screening tests (prothrombin time [PT] and activated partial thromboplastin time), hemostatic activation markers (thrombin–antithrombin complex [TAT] and prothrombin fragment 1+2 [PF1+2]), and von Willebrand factor (vWF) and its proteolytic enzyme ADAMTS-13; and determine the correlation between TG and NS severity, as reflected by the levels of proteinuria and albumin. Materials and Methods: This case–control cross-sectional study included 125 patients (n = 40, nephrotic range proteinuria; n = 45, NS; n = 40, remission) and 80 controls. Calibrated automated thrombogram assay (endogenous thrombin potential [ETP]) was performed to determine TG. TAT, PF1+2, vWF, and ADAMTS-13 were measured using enzyme-linked immunosorbent assay. Results: TG (ETP), TAT, PF1+2, and vWF levels were significantly higher in all of the patient groups (P < 0.0001) than in the control group. ADAMTS-13 levels were significantly lower in the NS group (P < 0.0001) than in the control group. Conclusion: Our findings confirm activation of the coagulation pathway in nephrotic patients. However, the degree of hypercoagulopathy (especially TG [ETP]) is positively correlated with proteinuria. Proteinuria could be considered an indirect indicator of the highest risk of thrombotic disease in patients with NS

Prevalence of von willebrand disease among university students in Riyadh, Saudi Arabia

BACKGROUND: von Willebrand disease (vWD) is the most common hereditary bleeding disorder, affecting up to 1% of the general population. OBJECTIVES: Estimating the prevalence of vWD among adolescents. DESIGN: This study was conducted between February 2014 and January 2016 on Saudi students in Riyadh. SETTINGS: We conducted an epidemiological survey on university students, using the standardized questionnaire based on molecular and clinical markers for the diagnosis and management of type 1 VWD. MATERIALS AND METHODS: All blood samples were tested for complete blood count, prothrombin time, partial thromboplastin time (PTT), and platelet function analyzer (PFA-100). MAIN OUTCOME MEASURES: Samples had an abnormal result of PTT and/or PFA-100 were tested for von Willebrand factor (vWF) antigen and factor VIII (FVIII) activity. SAMPLE SIZE: 2000 university students aged between 17 and 22 years were included. RESULTS: Of these students, 730 (36.5%) had reported bleeding symptoms, 326 (44.6%) had agreed to give blood samples, 116 (35.5%) samples had prolonged PTT (>41 s), 48 (14.7%) had prolonged PFA-100 adenosine diphosphate, 39 (11.9%) had prolonged PFA-100 epinephrine, and 72 (22.0%) had abnormal results in both PTT and PFA-100. Out of 275 samples tested for vWF (Ag and activity) and FVIII, 13 (3.9%) had reduced levels or nonfunction of vWF and 5 (1.6%) had reduced FVIII levels. After correlation with ABO blood group, only 5 (1.6%) cases were confirmed for vWD. The prevalence of vWD among Saudi adolescents in the selected student population was 1.5%. CONCLUSION: In this study, we report for the first time epidemiological survey of bleeding disorders in Arab ethnicity. LIMITATIONS: As this is a prevalence study, we have no limitations to discuss

Degree of concordance between peripheral blood leukemic blast count and mid induction bone marrow in childhood acute lymphoblastic leukemia

While different Pediatric ALL study groups have used varying definitions of early response (BM vs. PB, prophase vs. day 7 vs. day 14), all agree that it provides critical prognostic information. Bone Marrow aspiration and biopsy (BMA/B) is an invasive procedure requiring sedation or anesthesia, and an early/mid induction specimen may be difficult to interpret even by experienced hematopathologists. In this study we attempted to determine if there was a concordance between peripheral blood blast (PBB) clearance and the findings of the day 14 BMA/B, and whether day 7 PBB count could reliably replace a mid induction BMA/B. Clinical data for newly diagnosed pediatric (\u3c14 years) ALL patients between January 1999 and December 2001 were retrieved from our prospective database. Day 14 BMA/B slides were reviewed independently by two hematopathologist. For the total 165 patients, median age was 4 years, 53.9% were boys. Complete information was available for 151 of these patients and further analysis is based on this number. 124 (82.1%) were treated with 4 agents while the remainder received a 3-drug induction. 23 (18.5%) had positive PBB on D7, and 21 (13.9%) had \u3e5% blasts in the D14 BMA/B. The D7 PBB count could positively and negatively predict the D14 BMA/B 71.9% and 89.4% of the times, respectively. In conclusion, when the D14 BMA/B is used as a measure of early response, an absence of D7 PBB can reliably predict a negative BM, however persistence of PBB does not necessarily predict a sub-optimal BM response to early therapy. Therefore, patients without PBB on D7 may not require BMA/B on D14, therefore avoiding an invasive procedure for this group of patients