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Background The management of pregnant women with von Willebrand Disease (VWD) is complex as physiological pregnancy-induced increases in plasma von Willebrand Factor (VWF) may be blunted or absent. Women with VWD experience a heightened risk of postpartum haemorrhage (PPH) and special consideration must be given regarding neuraxial anaesthesia (NA) and the need for prophylaxis at time of delivery. These challenges are compounded by a lack of robust evidence to guide clinical decision making. Objectives & Methods To determine the current international clinical practises in the management of pregnancy for women with VWD, the International Society on Thrombosis and Haemostasis (ISTH) conducted an international survey of healthcare providers (HCP). Results 132 respondents from 39 countries were included in the final analysis. Variations in clinical practise were identified in antenatal (monitoring of plasma VWF and ferritin levels), peripartum (optimal plasma VWF target at delivery) and postpartum management (definitions used for PPH and postpartum monitoring). A key area of divergence was suitability for NA for women with type 2 and type 3 VWD, with many respondents advising against the use of NA even with VWF supplementation (29% type 2 VWD, 37% type 3 VWD) but others advising use once plasma VWF activity was was >50 IU/dL (57% type 2 VWD; 50% type 3 VWD). Conclusions This survey highlighted areas of uncertainty surrounding common management issues for pregnant women with VWD. These data underscore the need for international collaborative research efforts focused on peripartum management to improve care for pregnant women with VWD.

Background Bleeding disorders (BD) are under-recognized in adolescents with heavy menstrual bleeding (HMB). Objectives The lack of clinical guidelines and variable symptomatic management of HMB created the imperative to standardize HMB care to identify and manage BD in adolescents. Methods We convened an international working group (WG), utilized the results of a literature review to define knowledge gaps in HMB care, and used the collective clinical experience of the WG to develop care considerations for adolescents with BD and HMB. We then solicited input on the appropriateness of HMB care considerations from expert stakeholders representing hematology, adolescent medicine, and obstetrics-gynecology. We conducted an expert panel online, using the ExpertLens platform. During a 3-round online modified-Delphi process, the expert panel rated the appropriateness of 21 care considerations using a 9-point scale to designate care as appropriate (7-9), uncertain (4-6), or inappropriate (1-3) covering screening for BD, the laboratory work-up, and management of adolescents with BD that present with HMB. We used the RAND/UCLA appropriateness method to determine the existence of consensus among the interdisciplinary panel of experts. Results Thirty-nine experts participated in the panel. The experts rated fifteen HMB care considerations as appropriate, six as uncertain, and none as inappropriate. Conclusions The HMB care statements represent the first set of HMB care considerations in adolescents with BD, developed with broad expert input on appropriateness. Although likely to be of interest to a range of clinicians who routinely manage adolescents with HMB, additional research is required in many key areas.

Background Anticoagulated patients are particularly vulnerable to ADEs when they experience changes in medical acuity, pharmacotherapy, or care setting, and resources guiding care transitions are lacking. The New York State Anticoagulation Coalition convened a task force to develop a consensus list of requisite data elements (RDEs) that should accompany all anticoagulated patients undergoing care transitions. Methods A multidisciplinary panel of 15 anticoagulation experts voluntarily completed an iterative Delphi process. Resources were disseminated and deliberated via remote technology, with consensus achieved via blinded electronic polling. Results The panel reached consensus on a list of 15 RDEs for anticoagulation communication at discharge (the ACDC List). Consensus was rapidly achieved by the full panel on 13 elements, while 3 (2 of which were combined into 1 element) required multiple iterations and achieved consensus with votes from 8 available panelists. The elements encompassed a range of factors, including drug use and indications, previous exposure and duration of therapy, recent drug exposure and laboratory results and expectations for subsequent administration, therapy goals, patient education and comprehension, and expectations for clinical management. Twelve of the elements are applicable to any anticoagulant, and 3 are specific to warfarin. Conclusion The ACDC List identifies specific pieces of clinical information that a panel of anticoagulant experts agree should be communicated to downstream providers for all anticoagulated patients undergoing care transitions. Additional study is needed to objectively evaluate the ability of existing care systems to communicate the elements and to assess possible relationships between communication of the elements and clinical outcomes.

The diagnosis and treatment of von Willebrand disease (VWD) are challenging, in part because patients exhibit a wide range of bleeding patterns and manifestations (e.g. epistaxis, gingival bleeding, heavy menstrual bleeding, gastrointestinal bleeds, postoperative bleeding, hemarthroses) and in part because many tests are required to make an accurate diagnosis. Factor replacement therapies for VWD are the mainstay of treatment for patients who do not respond to desmopressin. They have gradually evolved from crude preparations of plasma proteins to plasma-derived concentrates containing both von Willebrand factor (VWF) and factor VIII (FVIII). However, varying amounts and quality of VWF and varying content of FVIII have contributed to the lack of a standardized approach to replacement therapy. More recently, the treatment of VWD has undergone a slow yet significant change from plasma-derived VWF/FVIII concentrates with VWF:ristocetin cofactor (RCo)/FVIII ratios ≤1, to those with VWF:RCo/FVIII ratios >10, to a recombinant VWF. This article reviews the evolution of factor replacement therapy for patients with VWD that has occurred over the last several decades. The availability of a greater variety of factor replacement therapies poses a challenge in terms of a standard algorithm of care but may help overcome the limitations of earlier treatments and allow treatment personalization according to individual patient needs.

Summary. Background: Inhibitors are a serious complication for patients with severe hemophilia A. Immune tolerance induction (ITI) is the primary method for eradicating these inhibitors. The role of type of concentrate and in particular the use of von Willebrand factor-containing, plasma-derived factor VIII (VWF/pd-FVIII) concentrate in primary or rescue ITI remains unclear. Objectives: To report retrospective collection of data on the use of a single VWF/pd-FVIII concentrate in primary and rescue ITI. Methods: Retrospective chart review of hemophilia A inhibitor patients at 11 US institutions who received VWF/pd-FVIII concentrate in primary or rescue ITI. Results: Primary ITI was carried out in eight inhibitor patients with a 75% complete and partial success. Secondary ITI was carried out in 25 inhibitor patients, with 52% attaining complete or partial success. Conclusions: This report represents the largest group of primarily pediatric, high-titer inhibitor patients treated with a single VWF/pd-FVIII concentrate. It adds retrospective data to the use of VWF-containing plasma-derived factor VIII concentrate in primary and rescue ITI, particularly in those patients with characteristics of poor response to ITI.

The evaluation of excessive menstrual bleeding carries a relatively high yield of discovering an underlying disorder of hemostasis in females. This review highlights important components in a structured history and outlines primary and secondary hematologic testing that should be considered in the evaluation of excessive menstrual bleeding.

The impact of von Willebrand disease in females is pronounced in terms of menorrhagia and postpartum haemorrhage. There is a very high proportion of von Willebrand disease patients with menorrhagia and associated anaemia, impairment of quality of life, including loss of time from work or school, and a high rate of the use of hysterectomy for ultimate control of the bleeding. The 'early' detection of von Willebrand disease in females may avert these complications. Consequently, there have recently been ongoing international efforts to determine the prevalence of von Willebrand disease in females presenting with menorrhagia, providing a prevalence of 7-20% combined from three studies including a total of 300 patients. Issues remain regarding the optimal dose/schedule of intranasal or subcutaneous desmopressin use for menorrhagia and the relative efficacy of anti-fibrinolytic agents. The proper role of oral contraceptives deserves further study in von Willebrand disease patients with menorrhagia as recent studies have paradoxically demonstrated a lower response rate in type 1 than type 2 or 3 von Willebrand disease. Despite the well-known adage of the 'gestational palliation' of von Willebrand disease, there is also a high proportion of postpartum haemorrhage in type 1 patients, especially after the 24 hour post-delivery period. This may occur despite a normalization of the factor VIIIc level in the third trimester, particularly in type 2 and 3 patients. The care-giver must be aware that haemorrhage can occur up to 5 weeks postpartum. In sum, studies over the past decade have documented a substantial impact of menses and childbirth on von Willebrand disease patients. These results should serve as a basis for interventional studies to reduce the morbidity of menstruation and childbirth.

Fourteen consecutive patients with chronic myelogenous leukemia (CML) blast crisis were treated with a more dose-intensive regimen of daunorubicin (70 mg/m2 per day on days 1-3) and cytosine arabinoside (200 mg/m2 per day as continuous infusion on days 1-9) than usually used in de novo acute myelogenous leukemia. The median age of the patients was 50 years (27-78 years). Eleven of 13 evaluable patients were aplastic at day 14 after a single course of therapy (11/13, 85%). Over-all response rate (complete + partial response) was 9/13 (69%). Restoration to chronic phase was achieved in 7/13 patients (54%) lasting a median of 78 days (49-235 days). However, four of these seven patients proceeded to bone marrow transplant (BMT) and so the true remission duration for this therapy cannot be determined. Treatment-related mortality was 4/14 (29%). Presently, four of nine patients evaluable are surviving post-induction, three S/P allogeneic BMT (0.6, 3.8, 5 years) and one patient S/P autologous BMT (3.3 years post-induction). These results of an intensive induction regimen achieving marrow aplasia in all except one patient to date warrants further study as the first step possibly towards BMT after CML blast crisis.

Pericarditis is a rare complication of chemotherapy. This report describes a patient who developed symptoms, signs, and electrocardiographic evidence of pericarditis following treatment with high dose cytarabine. The patient had no clinical or echocardiographic evidence of infection or leukemic involvement of the pericardium. Isolated pericarditis associated with high dose cytarabine has been rarely reported. This therapy is frequently used and, therefore, it seems prudent to alert physicians to this potential complication of cytarabine. The cardiopulmonary complications of cytarabine are also reviewed.

We report a case of adult de novo acute lymphoblastic leukemia (ALL) with unique cytogenetic abnormalities and discrepant morphologic and immunologic features. Morphology was L1 by the French-American-British classification, but flow cytometry was consistent with a mature B-cell phenotype. Cytogenetic analysis showed numerous chromosome abnormalities nonspecific for lymphoid neoplasm except for t(1;19) and t(14;18). The former is characteristic of pre-B-ALL and the latter is characteristic of follicular lymphoma. This is the first report of these two translocations occurring concurrently in ALL.

Myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms having ineffective production of one or more cell lines with accompanying morphologic abnormalities in common. This may include notably ringed sideroblasts, megaloblastic erythroid precursors, hypogranulation/hyposegmentation of the granulocytes, and micromegakaryocytes. The percentage of leukemic blasts is variable. Both primary (idiopathic) and secondary (therapy-related) MDS are discussed. The French-American-British (FAB) group classifies MDS into five subgroups. These groups are based on the presence of dysplasia, the number of monocytes, and the percentage of ringed sideroblasts and myeloblasts. Excellent correlation exists between the FAB subgroup and acute leukemic progression/survival. Outcome to a large degree is based on the percentage of blasts at diagnosis, the degree of pancytopenia, and dysplasia.