The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ACUTE LEUKEMIAS AND MYELODYSPLASTIC SYNDROMES
Luspatercept for MDS with ring sideroblasts (November 2022)
Luspatercept can improve red blood cell transfusion-independence (TI) in patients with myelodysplastic syndromes (MDS) with ring sideroblasts who did not respond to an erythropoiesis-stimulating agent (ESA), but the duration of benefit has been uncertain. Longer follow-up (median >2 years) of the phase 3 MEDALIST trial now reports that benefits of luspatercept increased over time . Compared with placebo, luspatercept achieved more ≥8-week TI (45 versus 16 percent, respectively); this and other hematologic outcomes improved over time, and there were no new toxicity signals. For patients with MDS with ring sideroblasts who fail to respond or are unlikely to respond to an ESA, luspatercept can achieve substantial, sustained TI. (See "Treatment of lower-risk myelodysplastic syndromes (MDS)", section on 'Luspatercept'.)
New, competing classification systems for hematologic malignancies (November 2022)
By consensus among pathologists for more than two decades, successive World Health Organization (WHO) fascicles ("blue books") have been used for classification of hematologic malignancies. However, in addition to a new WHO fascicle (the WHO 5th edition, WHO5 [2,3]), another classification scheme was published in 2022, the International Consensus Classification (ICC) [4,5]. Both classify hematologic malignancies according to cellular lineage, morphology, immunophenotype, and genetic/molecular findings, but there are notable differences in classification of acute myeloid leukemia and myelodysplastic syndromes and numerous differences in specific diagnostic criteria and names of otherwise identical entities. There is no current consensus and many pathologists may provide diagnoses according to both systems. We favor use of either the ICC or the WHO5 scheme rather than earlier classification systems. (See "Classification of hematopoietic neoplasms", section on 'Overview'.)
Ivosidenib plus azacitidine for IDH1-mutated AML in medically-unfit patients (October 2022)
Most patients with newly diagnosed acute myeloid leukemia (AML) who are not fit for intensive induction therapy receive treatment that includes a hypomethylating agent (HMA; ie, azacitidine or decitabine). A randomized trial now reports that in such patients who have IDH1-mutated AML, treatment with azacitidine plus ivosidenib (an inhibitor of mutant IDH1) achieved superior median survival compared with azacitidine plus placebo (24 versus 8 months) . The incidence of cytopenias and infections were similar in both trial arms. For patients with IDH1-mutated AML who are not eligible for intensive remission induction therapy, we recommend azacitidine plus ivosidenib, rather than an HMA alone. (See "Acute myeloid leukemia: Management of medically-unfit adults", section on 'IDH1-mutated AML'.)
Mutation-based models for estimating prognosis in MDS (September 2022)
Outcomes in myelodysplastic neoplasms/syndromes (MDS) are related to blood counts, percentage of marrow blasts, and various pathologic features. The International Prognostic Scoring System-Molecular (IPSS-M) is a validated mutation-based MDS prognostic model that incorporates more cytogenetic and molecular features than earlier models, such as the IPSS-Revised (IPSS-R) or the original IPSS. In an analysis of nearly 3000 patients with MDS, IPSS-M outperformed IPSS-R, reclassifying nearly half of patients and improving prognostic discrimination across all clinical end points . Moreover, IPSS-M was applicable for both untreated and treated patients. Although we favor the IPSS-M and other mutation based prognostic models, we still consider the IPSS-R to be acceptable for estimating prognosis in MDS; we no longer endorse the use of the original IPSS. (See "Prognosis of myelodysplastic neoplasms/syndromes (MDS) in adults", section on 'Choice of prognostic model'.)
ANEMIA AND OTHER RED CELL DISORDERS
Intrauterine transfusion for alpha thalassemia major (March 2023)
Alpha thalassemia major (ATM; loss of all four alpha globin genes) is usually incompatible with live birth unless intrauterine transfusions (IUT) are performed. In a series of 19 pregnancies with prenatally diagnosed ATM, all 14 fetuses treated with >2 IUT survived to delivery, while the 5 fetuses who did not receive IUT died in utero or shortly after birth . Earlier initiation of IUT correlated with higher neurodevelopmental scores. For patients electing to proceed with fetal therapy, IUT should be initiated as soon as technically possible (18 weeks at most fetal treatment centers). (See "Alpha thalassemia major: Prenatal and postnatal management", section on 'Intrauterine transfusions'.)
Hydroxyurea in sickle cell disease (February 2023)
A 2014 guideline recommends hydroxyurea for all infants, children, and adolescents with sickle cell disease and all adults with frequent vaso-occlusive complications, supported by decades of experience and strong evidence of reduced complications and improved survival . A new study documented increased hydroxyurea use from 7 percent in 2004 to 22 percent in 2019 . While demonstrating improvement, these findings suggest that persistent barriers to use remain. Strategies are needed to increase uptake of this effective therapy. (See "Hydroxyurea use in sickle cell disease", section on 'Eliminating barriers to appropriate therapy'.)
Improved survival for transfusion-dependent thalassemia (February 2023)
Survival for transfusion-dependent thalassemia (TDT) continues to improve with advances in managing iron overload and other complications. A new longitudinal cohort of 700 individuals with TDT managed by specialized centers in Italy reported improved survival in those born after 1985 (survival to age 30 in 93 percent, versus 84 percent in earlier birth cohorts) . Heart disease remains a major risk factor for – and cause of – death. Outcomes in other centers are poorer, emphasizing the need for multidisciplinary specialized centers in caring for individuals with TDT . (See "Management of thalassemia", section on 'Prognosis'.)
Treatment of iron deficiency in patients with heart failure (November 2022)
Patients with heart failure (HF) who are iron deficient should receive iron replacement, but the benefit of this therapy in patients who are not anemic is unclear. In a recent trial in nearly 1900 patients with HF who had an ejection fraction ≤45 percent, hemoglobin ≥9 g/dL, and evidence of iron deficiency (ie, low ferritin or low transferrin saturation), patients assigned to receive intravenous ferric derisomaltose had lower rates of mortality and hospitalization that did not reach statistical significance when compared with placebo . However, in aggregate, trials of iron replacement in similar patients suggest a favorable effect on reducing hospital admissions. Thus, for most patients with HF and iron deficiency (with or without anemia), we suggest iron replacement with intravenous iron. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure".)
CHRONIC LEUKEMIAS AND THE MYELOPROLIFERATIVE NEOPLASMS
Venetoclax in relapsed hairy cell leukemia (March 2023)
There are few options for treatment of relapsed or refractory hairy cell leukemia (HCL) and studies are investigating targeted therapies. In a single center report, five of six patients with multiply relapsed HCL responded to treatment with the BCL-2 inhibitor venetoclax, with or without rituximab . Among these five, progression-free survival (PFS) ranged from 23 to >53 months, and compared favorably with PFS after the most recent treatment. The main toxicities were worsening neutropenia, accompanied in some by fever and/or infection. While these initial data suggest that venetoclax has activity in HCL, further studies are needed prior to use outside of a clinical trial. (See "Treatment of hairy cell leukemia", section on 'Clinical trials and investigational therapies'.)
Zanubrutinib versus ibrutinib in relapsed CLL (December 2022, Modified January 2023)
The Bruton tyrosine kinase (BTK) inhibitors ibrutinib, acalabrutinib, and zanubrutinib are effective treatments for chronic lymphocytic leukemia (CLL). In a multicenter, open label, phase 3 trial (ALPINE) of >650 patients with relapsed or refractory CLL, when compared with ibrutinib, zanubrutinib improved progression-free survival and had less overall toxicity, including less cardiotoxicity . Overall survival data are immature. Based on these and other data, the US Food and Drug Administration has approved zanubrutinib for the treatment of chronic lymphocytic leukemia. For patients who are candidates for a BTK inhibitor, we now suggest zanubrutinib or acalabrutinib rather than ibrutinib. (See "Treatment of relapsed or refractory chronic lymphocytic leukemia", section on 'Zanubrutinib'.)
HEMATOPOIETIC CELL TRANSPLANTATION
Prednisone plus ibrutinib for chronic graft-versus-host disease (January 2023)
Systemic glucocorticoids (GCs) have long been the preferred initial treatment for moderate-to-severe chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic cell transplantation (HCT), but a second agent is often used to reduce adverse effects (AEs) of chronic GC therapy. The randomized iNTEGRATE trial in patients with moderate or severe cGVHD now reports that prednisone plus the Bruton tyrosine kinase inhibitor ibrutinib did not improve survival or response rates at 48 and 96 weeks after transplantation compared with placebo . However, there was a trend toward greater discontinuation of all immunosuppression for those treated with prednisone-ibrutinib. AEs were similar in both trial arms. For patients with severe cGVHD, we continue to suggest prednisone plus ruxolitinib (where available) as the preferred initial regimen. (See "Treatment of chronic graft-versus-host disease", section on 'Severe cGVHD'.)
HEMOSTASIS AND THROMBOSIS
Durability of gene therapy for hemophilia A (March 2023)
Promising initial results have been seen with factor VIII gene therapy for severe hemophilia A, but questions have been raised about durability of transgene expression. A new study that followed 134 individuals treated with the factor VIII gene therapy construct valoctocogene roxaparvovec for two years found continued efficacy during the second year (annualized bleeding rate 0.7, with declining factor VIII usage) . The mean factor VIII activity at week 104 was 22 international units per dL. Modeling studies provided an estimated half-life of 123 weeks and extrapolated mean factor VIII activity of 12 international units per dL at year 5. This construct is approved in Europe and is under review by the US Food and Drug Administration. (See "Gene therapy and other investigational approaches for hemophilia", section on 'Hemophilia A'.)
Extending low molecular weight heparin until closer to delivery (March 2023)
Some obstetricians replace low molecular weight (LMW) heparin with unfractionated heparin at 36 to 37 weeks of gestation to improve the patient's chances of receiving neuraxial anesthesia for labor and delivery, if desired. However, an analysis of data from the Highlow trial of LMW heparin prophylaxis in pregnancy found that most patients were eligible for neuraxial anesthesia at the unplanned onset of labor, including 82 percent of patients on low-dose and 61 percent of patients on intermediate-dose LMW heparin . Numbers of eligible patients were higher for planned labor (93 and 81 percent). These results support extended use of LMW heparin prophylaxis to 38 to 39 weeks or even until onset of labor in many individuals. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Switch to unfractionated heparin'.)
Extended half-life factor VIII for hemophilia A (February 2023)
Factor products that require less frequent intravenous administration are desirable for people with hemophilia. Factor VIII requires von Willebrand factor (VWF) for stability, and half-life extension has been limited due to the half-life of VWF. A new product circumvents this problem by fusing a form of factor VIII to the relevant VWF domain; in a study involving 133 individuals with severe hemophilia A, this product could be administered once weekly and dramatically reduced bleeding rates . This product was approved by the US Food and Drug Administration in February 2023, and availability is expected in April. (See "Gene therapy and other investigational approaches for hemophilia", section on 'Efanesoctocog alfa (factor VIII-VWF fusion)'.)
Apixaban and rivaroxaban after bariatric surgery (February 2023)
The anticoagulants apixaban and rivaroxaban are typically given at a fixed dose without drug monitoring. Two areas of concern are use in individuals with a very high body mass index (BMI) and use following bariatric surgery, which disrupts the gastrointestinal anatomy and might affect absorption. In a retrospective series of 102 adults who required anticoagulation for venous thromboembolism (VTE) after bariatric surgery, there were no episodes of VTE recurrence in individuals treated with apixaban and one recurrence in an individual treated with rivaroxaban; this individual had multiple other risk factors (foot ulcers, boot immobilization, and a BMI of 54 kg/m2) . When these anticoagulants are used in individuals with a high BMI and/or post-bariatric surgery, measurement of a trough level is used to ensure absorption. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'High BMI and post-bariatric surgery'.)
Romiplostim for ITP during pregnancy (February 2023)
Initial therapies for immune thrombocytopenia (ITP) during pregnancy (glucocorticoids and intravenous immune globulin [IVIG]) are usually effective and considered safe. In contrast, data on thrombopoietin receptor agonists (TPO-RAs) has been lacking. In a new study involving 92 pregnancies with romiplostim exposure, adverse pregnancy outcomes were similar to the general population . In pregnant individuals, we generally reserve TPO-RAs for refractory ITP or for those who cannot take glucocorticoids or IVIG. Individuals who become pregnant while taking a TPO-RA should have an individualized risk assessment. (See "Thrombocytopenia in pregnancy", section on 'ITP therapies'.)
Direct oral anticoagulants for treatment of venous thromboembolism in patients with brain tumors (January 2023)
Accumulating evidence in patients with brain tumors suggests that direct oral anticoagulants (DOACs) are associated with a lower risk of intracranial hemorrhage (ICH) than other forms of anticoagulation. In a recent observational study of 121 patients with glioblastoma and venous thromboembolism (VTE) who were treated with a DOAC or low molecular weight (LMW) heparin, the six-month incidence of clinically relevant ICH was lower with DOACs than LMW heparin (0 versus 24 percent), while rates of recurrent VTE were similar (0 versus 4 percent) . Based on these and other data, we favor DOACs as a safer and more convenient option in patients with primary and metastatic brain tumors who are selected to receive anticoagulation for VTE. We generally avoid anticoagulation in patients with intratumoral hemorrhage within the past four weeks or a remote history of a clinically significant ICH. (See "Treatment and prevention of venous thromboembolism in patients with brain tumors", section on 'Direct oral anticoagulants'.)
Dose of LMW heparin for VTE prevention in pregnancy (November 2022)
Low molecular weight (LMW) heparin is used for venous thromboembolism (VTE) prophylaxis during pregnancy and postpartum, but optimal dosing has been unclear. The Highlow trial evaluated dosing in 1110 pregnant individuals with a prior VTE receiving LMW heparin for VTE prophylaxis from the first trimester to six weeks postpartum . Compared with weight-adjusted intermediate dosing, those assigned to daily fixed low-dose (60 mg) LMW heparin had a slightly higher rate of VTE (1 percent in both groups antepartum, 2 versus 1 percent postpartum); the difference did not reach statistical significance. Bleeding risk was 4 percent in each group. While we continue to perform an individualized risk assessment for each patient, this trial provides reassurance for the efficacy of fixed low-dose LMH heparin, especially antenatally. (See "Use of anticoagulants during pregnancy and postpartum", section on 'LMW heparin'.)
Gastric protection during anticoagulation (November 2022)
Gastrointestinal (GI) bleeding can complicate anticoagulation, especially in individuals with prior GI bleeding, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and other risk factors. A new meta-analysis evaluating the benefit of proton pump inhibitors (PPIs) across six observational studies and one randomized trial found an association between PPI use and reduced upper GI bleeding (relative risk 0.67, 95% CI 0.61-0.74) . The correlation was strongest in individuals with NSAIDs or aspirin use and/or with a high bleeding risk score. UpToDate contributors suggest a PPI in individuals at high risk of upper GI bleeding who require anticoagulation. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Gastric protection'.)
Platelet transfusion thresholds (November 2022)
Prophylactic platelet transfusions are used to reduce bleeding risk in individuals with severe thrombocytopenia, but the efficacy and the optimal platelet count threshold remain unclear. A new systematic review analyzed data from seven randomized trials in individuals with hematologic malignancies or dengue virus infection and found a reduction in clinically important bleeding and a nonsignificant trend towards improved survival with platelet transfusion (administered at a variety of platelet thresholds) . The trials were conducted over several decades and had significant heterogeneity in populations and trial protocols. UpToDate contributors suggest prophylactic platelet transfusion for platelet counts <10,000/microL; transfusion at higher platelet counts is appropriate in individuals with certain conditions such as active infection or acute promyelocytic leukemia. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Supporting evidence'.)
LYMPHOMAS: HODGKIN AND NON-HODGKIN
Glofitamab for multiply relapsed or refractory diffuse large B cell lymphoma (January 2023)
Management of relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL) has changed rapidly in recent years, with approval of chimeric antigen receptor-T (CAR-T) cell therapy and various immunotherapies. In a study of 154 patients with r/r aggressive B cell lymphomas (mostly DLBCL), one-third of whom had previously received CAR-T cell therapy, approximately one-half experienced durable responses with glofitamab, a CD20 x CD3 bispecific T cell engage (BiTE) monoclonal antibody . More than one-half of patients had grade ≥3 adverse events (AEs; mostly cytopenias), but few had severe cytokine release syndrome or neurologic AEs; fatal AEs occurred in 3 percent. Approval is currently pending in both the United States and Europe, but glofitamab is a treatment option for r/r DLBCL, including patients previously treated with CAR-T cell therapy. (See "Diffuse large B cell lymphoma (DLBCL): Second or later relapse or patients who are medically-unfit", section on 'Glofitamab'.)
Mosunetuzumab for multiply relapsed follicular lymphoma (August 2022, Modified January 2023)
Mosunetuzumab is a bispecific T cell engager (BiTE) monoclonal antibody directed at both CD20 on follicular lymphoma (FL) cells and CD3 on cytotoxic T cells. In a single-arm, multicenter phase 2 study of mosunetuzumab in 90 patients with FL relapsed after at least two prior lines of treatment, there were high response rates (60 percent complete, 20 percent partial), with a median duration of response of 23 months . The most common adverse event was cytokine release syndrome, which was predominantly grade 1 or 2 and confined to the first cycle. These results led to approval of mosunetuzumab by the US Food and Drug Administration and European Medicines Agency for this population. Where available, we consider mosunetuzumab an option for patients with multiply relapsed FL with short prior remission durations (eg, <24 months). (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Mosunetuzumab'.)
Brentuximab vedotin for treatment of advanced classic Hodgkin lymphoma in children (November 2022)
Intensification of therapy for advanced classic Hodgkin lymphoma (cHL) in children can improve outcomes, but these benefits must be balanced against the risk for increased toxicity from combination chemotherapy, with or without radiation therapy. A recent randomized trial demonstrated that, for children with advanced cHL (stage IIB with bulky disease, stage III, stage IV), the addition of brentuximab vedotin (an anti-CD30 monoclonal antibody conjugate) to standard intensive combination chemotherapy improved three-year event-free survival (92 versus 83 percent) with no increase in toxicity . Longer-term follow-up is needed to determine if there is a difference in overall survival or late toxicity, such as growth and development delays or second cancers. For children with advanced cHL, we recommend addition of brentuximab vedotin, when available, to the combination chemotherapy regimen. (See "Overview of Hodgkin lymphoma in children and adolescents", section on 'High-risk disease'.)
MULTIPLE MYELOMA AND OTHER PLASMA CELL DISORDERS
Prevalence of smoldering multiple myeloma (March 2023)
There are limited data regarding the prevalence of smoldering multiple myeloma (SMM) since it is an asymptomatic condition without a routine screening program. The Icelandic iStopMM population-based study screened >75,000 adults over age 40 . The prevalence of SMM was 0.5 percent overall. Rates were higher in males and increased with age from <0.25 percent in those under 50 years to 1 percent in those over 80 years. There is no current role for routine screening. Further follow-up is needed to determine whether early detection and intervention improves patient outcomes. (See "Smoldering multiple myeloma", section on 'Epidemiology'.)
Posttransplant maintenance in multiple myeloma (March 2023)
For patients with multiple myeloma (MM), autologous hematopoietic cell transplantation (HCT) is followed by at least two years of maintenance therapy to delay progression. In a randomized, open-label, phase 3 trial (ATLAS), post-HCT maintenance with carfilzomib, lenalidomide, and dexamethasone (KRd) improved progression-free survival over lenalidomide alone (median, 59 versus 41 months), although with more logistical complexity and serious adverse events (30 versus 22 percent) . Given their relatively favorable course, we offer patients with standard-risk MM single-agent lenalidomide to minimize toxicity, and reserve combination maintenance for those with high-risk MM. (See "Multiple myeloma: Use of hematopoietic cell transplantation", section on 'High-risk disease'.)
CAR-T cell therapy in multiply relapsed refractory multiple myeloma (March 2023)
Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapies are an option for patients with relapsed or refractory multiple myeloma (MM) following at least four lines of systemic therapy, and one of our preferred treatments for penta-refractory MM (algorithm 1). In a multicenter, open-label, phase 3 trial (KarMMa-3) that included >385 adults with multiply relapsed MM refractory to the last regimen, the anti-BCMA CAR-T cell idecabtagene vicleucel substantially improved progression-free survival over standard chemotherapy (median 13 versus 4 months), albeit with increased toxicity, including treatment-related deaths . Overall survival data are immature. The use of BCMA-directed therapies is individualized, weighing disease tempo, availability of other treatments, and expected toxicity. (See "Multiple myeloma: Treatment of third or later relapse", section on 'Chimeric antigen receptor T cells'.)
Belantamab mafodotin withdrawn from market (December 2022)
Belantamab mafodotin is being withdrawn from the market beginning November 2022, although it remains accessible through the manufacturer for patients who started treatment prior to its withdrawal . The antibody drug conjugate targeting B-cell maturation antigen (BCMA) had received accelerated approval in the United States for patients with relapsed or refractory multiple myeloma (MM) based on response data from two uncontrolled open-label trials (DREAMM-1 and DREAMM-2). However, initial results of a randomized phase 3 trial (DREAMM-3) of belantamab mafodotin versus pomalidomide and dexamethasone in relapsed or refractory MM have not confirmed clinical benefit, leading to market withdrawal. (See "Multiple myeloma: Treatment of third or later relapse", section on 'Belantamab mafodotin'.)
Bispecific T cell engager (BiTE) teclistamab in multiple myeloma (November 2022)
Therapies that target the B cell maturation antigen (BCMA) are a preferred treatment option for patients with penta-refractory multiple myeloma (MM), defined as disease refractory to an anti-CD38 monoclonal antibody, lenalidomide, pomalidomide, bortezomib, and carfilzomib (algorithm 1). In a single-arm, phase 2, multicenter trial (MajesTEC-1) of the first-in-class anti-BCMA bispecific T-cell engager (BiTE) teclistamab in multiply relapsed MM, objective responses were seen in 63 percent, with an estimated progression-free survival of 11 months . At least one grade 3 or 4 toxicity was reported in 95 percent of patients, with hematologic toxicity being most common. Cytokine release syndrome occurred in 73 percent and was usually grade 1 or 2. Based on this data, teclistamab has received accelerated approval by the US Food and Drug Administration for treatment of adults with relapsed, refractory MM after four or more lines of systemic therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody . The use of teclistamab and other BCMA-directed therapies is individualized, weighing disease tempo, availability of other treatments, and expected toxicity. (See "Multiple myeloma: Treatment of third or later relapse".)
Er blood group system (February 2023)
Research continues to identify new connections between blood group systems, associated proteins, and clinical outcomes. A recent study has determined that the Er blood group system is encoded by the PIEZO1 gene . The Piezo1 protein is a mechanosensitive channel (piezo is Greek for pressure); it controls red blood cell volume in response to mechanical tension. Pathogenic variants in PIEZO1 can cause hereditary stomatocytosis or xerocytosis. Er blood group antigens appear to play roles in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn, but further research is needed. (See "Red blood cell antigens and antibodies", section on 'Er blood group system'.)
Prothrombin complex concentrate versus plasma for coagulopathy and bleeding after cardiopulmonary bypass (September 2022)
Unactivated prothrombin complex concentrate (PCC) is used to rapidly correct warfarin anticoagulation. Observational studies have described off-label use of PCC to treat surgical coagulopathic bleeding, but supporting data are limited. One randomized trial compared administration of PCC 15 International Units/kg with fresh frozen plasma (FFP) 10 to 15 mL/kg in 100 patients who had excessive microvascular bleeding with prothrombin time (PT) >16.6 seconds and international normalized ratio (INR) >1.6 after cardiac surgery with cardiopulmonary bypass . Overall efficacy and safety were comparable between PCC and FFP, and patients receiving PCC had improved correction of PT and INR. Before considering administration of PCC or FFP, we treat other causes of intractable bleeding (eg, surgical sources, thrombocytopenia, low fibrinogen levels, platelet dysfunction). (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Prothrombin complex concentrate (PCC) products'.)
Anticoagulation in hereditary hemorrhagic telangiectasia (February 2023)
Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder with increased risk of bleeding, but individuals with HHT also have an increased risk of thrombosis and may require anticoagulation. In a new study that followed 119 individuals with HHT receiving antithrombotic therapy, the rate of dose reduction or premature drug discontinuation was 50 percent . Multivariate analysis identified prior gastrointestinal bleeding as the main risk factor for dose reduction or discontinuation; the choice of anticoagulant (warfarin or a direct oral anticoagulant [DOAC]) was not predictive. Individuals with HHT can receive anticoagulation but require especially close monitoring. Current guidelines suggest warfarin if an oral anticoagulant is needed, but DOACs may be considered on a case-by-case basis. (See "Hereditary hemorrhagic telangiectasia (HHT): Routine care including screening for asymptomatic AVMs", section on 'Individuals who require anticoagulation (VTE and AF)'.)
Plasminogen eye drops for ligneous conjunctivitis (February 2023)
Ligneous conjunctivitis is caused by a pseudomembrane that forms on the eyes and can threaten vision. It is common in individuals with plasminogen deficiency (PLGD). Treatments include systemic or ophthalmologic plasminogen replacement. In a series of patients from Italy, plasminogen concentrate eye drops caused resolution of the lesions over the course of several weeks without recurrence . Individuals with manifestations of PLGD affecting other organ systems require systemic plasminogen concentrate or plasma transfusions. (See "Plasminogen deficiency", section on 'Ophthalmic and topical'.)
Iptacopan for breakthrough hemolysis with paroxysmal nocturnal hemoglobinuria (January 2023)
The C5 complement inhibitors (C5i), ravulizumab and eculizumab, effectively control paroxysmal nocturnal hemoglobinuria (PNH)-related symptoms, prevent thromboses, and control intravascular hemolysis, but up to one-fifth of patients experience breakthrough symptoms due to extravascular hemolysis. Newer agents that inhibit other components in the complement cascade, such as pegcetacoplan and iptacopan, can control both intravascular and extravascular hemolysis. In preliminary results of a randomized trial of patients with residual anemia while receiving a C5i, iptacopan achieved superior transfusion independence and quality of life compared with continued C5i therapy, without additional toxicity . Iptacopan has received breakthrough therapy designation from the US Food and Drug Administration and orphan drug designation from the European Medicines Agency, but it is not yet commercially available. For patients with PNH and breakthrough hemolysis while receiving a C5i, we suggest treatment with pegcetacoplan or iptacopan. (See "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria", section on 'Management of breakthrough hemolysis'.)
Drainage or splenectomy for splenic abscess (November 2022)
Splenic abscess is an uncommon infection that typically results from a hematogenous source such as endocarditis. Along with broad-spectrum antibiotics, a procedure is often needed to remove the fluid collection. A new systematic review of splenic abscess treatment in nearly 600 patients found that approximately half were treated with percutaneous drainage and half with splenectomy . There were no statistically significant differences in mortality or complications. Drainage is less invasive and was associated with trends toward lower mortality and complication rates, but this may have reflected differences in patient populations or local expertise. The choice of procedure is individualized; percutaneous drainage may be preferable to some individuals if feasible. (See "Evaluation of splenomegaly and other splenic disorders in adults", section on 'Management (abscess/infarction)'.)
IVIG for vaccine-induced immune thrombotic thrombocytopenia (October 2022)
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral-vectored COVID-19 vaccines that presents with thrombocytopenia and thrombosis. Emerging evidence on management continues to support a role for intravenous immune globulin (IVIG) as a component of therapy, along with anticoagulation. In a new nonrandomized study involving 99 individuals with VITT presenting with cerebral venous thrombosis, receipt of IVIG was associated with lower mortality (29 versus 70 percent) . In contrast, the choice of anticoagulant (heparin versus a nonheparin agent) and receipt of a platelet transfusion were not associated with statistically different mortality rates. We continue to suggest IVIG plus a nonheparin agent, especially if there is concern for possible heparin-induced thrombocytopenia (HIT; including delayed or spontaneous HIT). (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'IVIG'.)
1 : Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts.
2 : The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms.
3 : The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms.
4 : International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data.
5 : The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.
8 : The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.
9 : Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members.
10 : Trends in blood transfusion, hydroxyurea use, and iron overload among children with sickle cell disease enrolled in Medicaid, 2004-2019.
11 : Overall and complication-free survival in a large cohort of patients withβ-thalassemia major followed over 50 years.
12 : The influence of treatment in specialized centers on survival of patients with thalassemia major.
13 : Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial.
16 : Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study.
18 : Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study.
22 : Risk of intracranial hemorrhage with direct oral anticoagulants vs low molecular weight heparin in glioblastoma: A retrospective cohort study.
23 : Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.
24 : Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis.
25 : Prophylactic platelet transfusions versus no prophylaxis in hospitalized patients with thrombocytopenia: A systematic review with meta-analysis.
27 : Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study.
30 : Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial.
35 : Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens.
36 : Prothrombin Complex Concentrate vs Plasma for Post-Cardiopulmonary Bypass Coagulopathy and Bleeding: A Randomized Clinical Trial.
37 : Safety, tolerability, and effectiveness of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia.
39 : Oral Monotherapy with Iptacopan, a Proximal Complement Inhibitor of Factor B, Has Superior Efficacy to Intravenous Terminal Complement Inhibition with Standard of Care Eculizumab or Ravulizumab and Favorable Safety in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia: Results from the Randomized, Active-Comparator-Controlled, Open-Label, Multicenter, Phase III APPLY-PNH Study
40 : Splenectomy versus Imaging-Guided Percutaneous Drainage for Splenic Abscess: A Systematic Review and Meta-Analysis.
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