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What's new in hematology
Official reprint from UpToDate® ©2016 UpToDate®
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What's new in hematology
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: Dec 01, 2016.

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.


Inotuzumab ozogamicin in acute lymphoblastic leukemia (June 2016)

Inotuzumab ozogamicin is an investigational anti-CD22 monoclonal antibody conjugated to calicheamicin; it has demonstrated activity in relapsed/refractory acute lymphoblastic leukemia (ALL). Early results are available from an international open-label, randomized phase 3 trial that compared inotuzumab ozogamicin versus intensive chemotherapy in 326 patients with relapsed/refractory ALL [1]. Inotuzumab ozogamicin resulted in a higher percentage of patients achieving a complete response (81 versus 29 percent), many of whom attained minimal residual disease negativity. There was a small improvement in median progression-free survival (five versus two months) and overall survival (eight versus seven months). Inotuzumab ozogamicin results in high rates of deep response in this setting, but the majority of patients will relapse if no further therapy is given. Further study is necessary to better elucidate the best way to incorporate this drug into the treatment of patients with ALL. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults", section on 'Inotuzumab ozogamicin'.)


Rhabdomyolysis and sickle cell trait (August 2016)

Sickle cell trait is a benign carrier condition with a normal life expectancy. However, concerns have been raised regarding an increased risk of rhabdomyolysis and sudden death with prolonged physical activity. These risks were addressed in a cohort study of almost 50,000 black soldiers in the United States army for whom sickle cell trait status and other clinical information was available [2]. While the risk of rhabdomyolysis was increased (hazard ratio, 1.5), this magnitude of risk is similar to that conferred by obesity or smoking and less than that due to antipsychotic or statin medications. Mortality was not increased over that in black soldiers without sickle cell trait, and the sole death from rhabdomyolysis occurred in an individual without sickle cell trait. Interventions to reduce exertion-related injuries should be aimed at all athletes and members of the military, regardless of sickle cell trait status. (See "Sickle cell trait", section on 'Rhabdomyolysis and sudden death during strenuous physical activity'.)


Ibrutinib in chronic lymphocytic leukemia with del(17p) (October 2016)

Patients with chronic lymphocytic leukemia (CLL) with del(17p) or a TP53 mutation have low response rates and high relapse rates following treatment with most standard therapies. Subset analyses of larger studies suggested that this difficult-to-treat group could attain better outcomes with the Bruton's tyrosine kinase inhibitor ibrutinib. This was confirmed in a multicenter, single-arm trial of ibrutinib in 144 patients with relapsed/refractory CLL with del(17p) that showed an overall response rate of 83 percent and estimated rates of progression-free and overall survival at two years of 63 and 75 percent, respectively [3]. These results support our preference for single agent ibrutinib as the initial therapy in most patients with CLL demonstrating del(17p) or a TP53 mutation. (See "Treatment of relapsed or refractory chronic lymphocytic leukemia", section on 'Ibrutinib'.)

Bendamustine plus rituximab versus FCR in CLL (July 2016)

Nonrandomized trials have suggested that the combination of bendamustine plus rituximab (BR) is slightly less effective, but better tolerated than, fludarabine, cyclophosphamide, and rituximab (FCR) for the initial treatment of chronic lymphocytic leukemia (CLL). In a multicenter, open-label noninferiority trial, 564 adults with previously untreated CLL without del(17p) and without significant comorbidities were randomly assigned to FCR versus BR [4]. Despite being associated with more severe toxicities and dose reductions, FCR improved median progression-free survival by approximately 13 months. At a median follow-up of 37 months, this has not yet translated into an improvement in overall survival. FCR remains our preferred treatment regimen for younger adults with previously untreated CLL without del(17p). Given its better tolerability, BR is an acceptable alternative for younger adults with decreased renal function or other comorbidities. (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia", section on 'Bendamustine-based therapy'.)

Midostaurin in systemic mastocytosis (June 2016)

Case reports have described dramatic responses in patients with systemic mastocytosis (SM) treated with the multikinase/KIT inhibitor midostaurin. Two prospective trials of midostaurin have now described responses in 60 to 70 percent of patients with advanced SM [5,6]. Treatment resulted in reversal of organ damage (cytopenias, liver dysfunction) and decreases in bone marrow mast cell burden and serum tryptase levels. Responses were observed regardless of KIT D816V status, prior therapy, or the presence of an associated hematologic neoplasm. Midostaurin is being evaluated by drug regulatory agencies, but is as yet unavailable. (See "Systemic mastocytosis: Treatment and prognosis".)

Vascular disease in patients with CML taking tyrosine kinase inhibitors (June 2016)

For the initial treatment of chronic myeloid leukemia (CML), the second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib are able to achieve faster and deeper responses than imatinib, but have a different toxicity profile, including increased cardiovascular toxicity. A retrospective cohort study used a Swedish population-based registry to analyze the risk of vascular events in 896 patients with chronic-phase CML treated with imatinib, dasatinib, or nilotinib [7]. When compared with age- and sex-matched controls, patients treated with any TKI had an increased risk of vascular events, but the association was greater with the second-generation agents. Event rates for myocardial infarction among patients treated with nilotinib, dasatinib and imatinib were 29, 19, and 8 per 1000 person-years, respectively. These findings underscore the importance of screening for and optimal management of traditional cardiac risk factors. Although it is not known whether anticoagulation helps, many clinicians offer low-dose aspirin for general cardiovascular prophylaxis in patients taking TKIs. (See "Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia", section on 'Vascular disease'.)


Umbilical cord blood transplant in minimal residual disease positive AML (September 2016)

For patients with acute myeloid leukemia (AML) undergoing transplant who do not have a related donor, it is not known if the presence of minimal residual disease (MRD) should influence donor choice. In one retrospective study, leukemia patients with MRD prior to transplant had less relapse and better survival with an unrelated umbilical cord blood (UCB) transplant than with peripheral blood progenitor cell or bone marrow from an HLA-matched unrelated donor or an HLA-mismatched unrelated donor [8]. In contrast, a benefit for UCB transplant was not seen among those without MRD. Further analysis suggested that the use of UCB abrogated the negative impact of MRD on patient outcome. Further trials are needed to confirm these findings and evaluate whether other donor groups (eg, haploidentical transplant) impact outcomes in patients with MRD. (See "Donor selection for hematopoietic cell transplantation", section on 'Disease status'.)

Virus-specific T cell infusions for patients with primary immunodeficiencies and hematopoietic cell transplant (June 2016)

Viral infections, particularly with cytomegalovirus, Epstein-Barr virus, and adenovirus, are a leading cause of death in patients with severe combined immunodeficiency (SCID) and other forms of moderate-to-severe primary immunodeficiency (PID), both before and after hematopoietic cell transplantation (HCT). Investigational infusions of virus-specific T cells (VST) from either stem cell donors or third-party donors have been evaluated to treat and/or prevent these life-threatening viral infections. One retrospective series examined 26 patients with a PID requiring HCT who had at least one documented serious viral infection and were treated with VST either before or after HCT [9]. Complete or partial antiviral response was seen in 76 to 100 percent of patients, depending upon the particular virus. An additional 10 patients were treated preventively with VST prior to HCT. Of these, eight remained free of the most common serious viral infections. This therapy is still experimental, but commercial entities are developing these cellular products and they may be available for more widespread use in a few years. (See "Severe combined immunodeficiency (SCID): An overview", section on 'Treatment'.)


Syncope and pulmonary embolus (October 2016)

While pulmonary embolus (PE) has generally been considered to be a relatively rare cause of syncope, a recent study reported a 17 percent prevalence of PE among patients admitted to hospital with syncope, and a 25 percent prevalence among those without an alternative etiology for syncope [10]. Two-thirds of patients with syncope secondary to PE had thrombus located in the mainstem or lobar arteries, suggesting that syncope may indicate a high burden of thrombus. The study underscores the importance of syncope as a presenting manifestation of clinically significant PE. (See "Clinical presentation, evaluation, and diagnosis of the adult with suspected acute pulmonary embolism", section on 'History and examination'.)

Risk of inherited thrombophilia and central venous catheter-associated venous thromboembolism in children (September 2016)

The majority of venous thromboembolism (VTE) in children is associated with central venous catheter (CVC) use. The association between inherited thrombophilia (IT) and CVC-related VTE is unclear. A recent systematic review and meta-analysis found that IT is associated with an increased likelihood of CVC-associated VTE (odds ratio 3.2 [95% CI 1.6-6.5]) [11]. However, the meta-analysis was limited by significant heterogeneity among studies and a relatively high prevalence of elevated factor VIII, which may represent an inherited disorder or may be acquired. The prevalence of most other IT traits in the meta-analysis was low and their associations with CVC-related VTE were relatively weak. The available evidence is insufficient to support routinely performing IT testing to inform management decisions in children with CVC-related VTE. (See "Screening for inherited thrombophilia in children", section on 'First episode of CVC-related VTE'.)

Investigational reversal agent for factor Xa inhibitors (September 2016)

Andexanet alfa is an investigational reversal agent for anticoagulants that inhibit factor Xa, including the oral direct factor Xa inhibitors, low molecular weight heparins, and fondaparinux. It is a catalytically inactive form of factor Xa that is administered intravenously as a bolus followed by a two-hour infusion. A recent preliminary report from a study in patients with factor Xa inhibitor-associated major bleeding (ANNEXA-4) has now demonstrated efficacy of andexanet, with excellent or good hemostasis in 37 of 47 patients and reduced anti-factor Xa activity for several hours [12]. Potential concerns include a possible increased risk of thrombosis, although most patients in the study were elderly, had atrial fibrillation and/or risk factors for venous thromboembolism, and were not receiving anticoagulation at the time they developed a thrombus. ANNEXA-4 is ongoing; andexanet is not yet available for clinical or compassionate use. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antidotes under development'.)

Dosing of direct oral anticoagulants in obese patients (June 2016)

Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject [13]. The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) ≤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight ≥120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)

Risk of inhibitors in hemophilia A (June 2016)

Individuals with hemophilia who receive coagulation factor infusions are at risk of developing an autoantibody to the factor (a factor inhibitor); this occurs in approximately 25 to 30 percent of individuals with severe hemophilia A. The SIPPET trial (Survey of Inhibitors in Plasma-Product Exposed Toddlers) is the first randomized trial to evaluate the risk of inhibitors with recombinant versus plasma-derived factor VIII products [14]. In SIPPET, 264 children who required factor VIII infusions were randomly assigned to receive a recombinant or a plasma-derived product. Inhibitors were seen more frequently with the recombinant products (37 versus 23 percent). The mechanism of this difference is unknown; the presence of von Willebrand factor in the plasma-derived products or the use of non-human cell lines to produce the recombinant products has been suggested. These results may not apply to recombinant products made in human cell lines or those engineered to have extended half-lives. (See "Factor VIII and factor IX inhibitors in patients with hemophilia", section on 'Recombinant versus plasma-derived products'.)

Investigational laboratory assay for multiple anticoagulants (June 2016)

The prothrombin time (PT) with international normalized ratio (INR) and the activated partial thromboplastin time (aPTT) are used to monitor warfarin and heparin therapy, but these tests are not adequate for assessing the presence or therapeutic effect of direct thrombin inhibitors or direct factor Xa inhibitors. A modified form of the PT that uses highly diluted thromboplastin, designated dFiix-PT, has been developed [15]. In a preliminary study, this assay was able to detect and quantify unfractionated and low molecular weight heparins, vitamin K antagonists, and direct oral anticoagulants. If validated, this test could potentially greatly simplify anticoagulant testing. (See "Clinical use of coagulation tests", section on 'Prothrombin time (PT) and INR'.)

Role of platelet transfusions in bleeding associated with antiplatelet agents (May 2016)

The role of platelet transfusion in patients with antiplatelet agent-associated bleeding has been unclear. A recent randomized trial compared platelet transfusions with standard care in 190 individuals with intracerebral hemorrhage (ICH) in the setting of aspirin or other antiplatelet agents [16]. Compared with those assigned to standard care, individuals who received platelet transfusions had a higher rate of a composite endpoint of death or lower score on the modified Rankin Scale for functional independence. When analyzed separately, the increase in mortality did not reach statistical significance. Serious adverse events were more frequent in the platelet transfusion arm, and ICH enlargement was similar in both arms at approximately 15 percent. Despite these results, such cases can be complex, and we continue to favor an individualized approach. (See "Clinical and laboratory aspects of platelet transfusion therapy", section on 'Platelet function defects'.)


Acquired C1 inhibitor deficiency in lymphoma patients (August 2016)

Acquired C1 inhibitor deficiency is a rare disorder that causes episodes of angioedema that are unresponsive to epinephrine or antihistamines and can be fatal if the airway is compromised. In previous series of patients with acquired angioedema, 30 to 40 percent were found to have a malignancy of some type, most commonly a non-Hodgkin lymphoma (NHL). However, the overall prevalence of acquired C1 inhibitor deficiency in patients with lymphoma was unknown. In a new retrospective study of 131 patients with different types of lymphoma, patients were screened at the time of lymphoma diagnosis for deficiency and dysfunction of C1 inhibitor [17]. Four patients (3 percent) were symptomatic with episodic swelling and all four had both functional tests and levels of C1 inhibitor that were below 50 percent of normal. Three of these four had splenic marginal cell lymphoma. Another 10 patients had abnormal C1 inhibitor function but had not developed angioedema. This study provides an initial estimate of the prevalence of acquired C1 inhibitor deficiency in lymphoma patients and suggests that those with splenic marginal cell lymphoma may be at particular risk. (See "Acquired C1 inhibitor deficiency: Clinical manifestations, epidemiology, pathogenesis, and diagnosis", section on 'Lymphoproliferative disorders and B cell malignancies'.)

PET/CT-adapted therapy in advanced Hodgkin lymphoma (June 2016)

Mid-treatment positron emission tomography/computed tomography (PET/CT) has prognostic value in patients with Hodgkin lymphoma (HL), and initial studies suggest that treatment may be safely deescalated in early responders. In a large trial, 935 patients with advanced-stage HL who achieved a "negative" PET/CT after two cycles of combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were randomly assigned to receive four more cycles of ABVD or four cycles of doxorubicin, vinblastine, and dacarbazine (AVD) [18]. AVD and ABVD resulted in similar rates of progression-free survival at three years (PFS, 84 versus 86 percent), although the 95% confidence intervals included a decrease in PFS with AVD of 5.3 percent. Decisions for an individual patient must take into account the risk of pulmonary toxicity with further bleomycin versus a potentially small increase in relapse with bleomycin omission. Omission in those with a "negative" PET/CT is most attractive for patients with additional risk factors for bleomycin toxicity (eg, older age, underlying pulmonary disease, active smokers). Application of this approach must pay careful attention to the methodology used including the timing of PET/CT and cutoff values used to determine "negative" scans. (See "Initial treatment of advanced (stage III-IV) classical Hodgkin lymphoma", section on 'Response adapted therapy'.)

Maintenance rituximab after bendamustine plus rituximab in mantle cell lymphoma (June 2016)

Maintenance rituximab improves progression-free survival (PFS) and may improve overall survival in patients with mantle cell lymphoma (MCL) treated with R-CHOP induction, but its role after induction with bendamustine plus rituximab (BR) is not well understood. In a preliminary report, presented in abstract form, a randomized phase 2 trial comparing two years of maintenance rituximab versus observation in 168 patients with newly diagnosed MCL treated with BR induction showed no significant difference in PFS at a median follow-up of 59 months (HR 0.71; 95% CI 0.41-1.23; median 55 versus 72 months) [19]. For patients with newly diagnosed MCL who have had at least a partial response to initial therapy and are not eligible for autologous hematopoietic cell transplantation (HCT), the decision to use maintenance rituximab must take into account the initial therapy administered. Given the lack of a PFS benefit in this randomized trial, we suggest observation rather than maintenance following BR induction. In contrast, for those receiving R-CHOP induction, we suggest the use of maintenance rituximab until progression, rather than observation with treatment at the time of progression. (See "Initial treatment of mantle cell lymphoma", section on 'Maintenance therapy'.)

R-CHOP/R-DHAP for mantle cell lymphoma (June 2016)

Nonrandomized prospective trials have suggested high rates of deep responses in patients with mantle cell lymphoma (MCL) treated with alternating cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) followed by autologous hematopoietic cell transplantation (HCT). A randomized trial in 497 younger adults with previously untreated MCL compared six cycles of this regimen versus six cycles of R-CHOP, both followed by autologous HCT [20]. After a median follow-up of six years, R-CHOP/R-DHAP resulted in longer time to treatment failure (median nine versus four years), but this has yet to translate into a statistically significant survival benefit (HR 0.78; 95% CI 0.57-1.07). R-CHOP/R-DHAP was associated with higher rates of hematologic toxicity, febrile neutropenia, and renal toxicity. We do not routinely use R-CHOP/R-DHAP due to toxicity concerns and lack of a proven survival benefit. (See "Initial treatment of mantle cell lymphoma", section on 'Conventional chemoimmunotherapy'.)


Daratumumab-based regimens in relapsed multiple myeloma (October 2016, Modified October 2016)

Two recent multicenter randomized trials including over 1000 patients have demonstrated large improvements in progression-free survival (PFS) when the anti-CD38 monoclonal antibody daratumumab is added to standard regimens in relapsed multiple myeloma. The addition of daratumumab to either lenalidomide plus dexamethasone (POLLUX trial) or to bortezomib plus dexamethasone (CASTOR trial) resulted in substantially improved response rates and PFS with a mild to moderate increase in toxicity [21,22]. Mostly mild infusion reactions were common with the first infusion, but rarely resulted in drug discontinuation. Overall survival data are not yet mature. Based on these results we now recommend a daratumumab-based regimen for the treatment of first relapse in myeloma. (See "Treatment of relapsed or refractory multiple myeloma", section on 'Daratumumab'.)


Transfusion outcomes with "fresh" versus "old" blood (November 2016)

The INFORM trial (Informing Fresh versus Old Red Cell Management) is the largest trial to compare clinical outcomes with "fresh" versus "old" blood [23]. In INFORM, over 20,000 hospitalized adults who required transfusion were randomly assigned to receive "old" red blood cells (RBCs; stored for a mean of 24 days) or "fresh" RBCs (stored for a mean of 13 days). There were no differences in mortality or hospital length of stay. Smaller trials in adults, children, and neonates have also concluded that outcomes are unaffected by RBC storage duration. (See "Red blood cell transfusion in adults: Storage, specialized modifications, and infusion parameters", section on 'Clinical relevance of storage time'.)

Updated guideline and meta-analysis on hemoglobin thresholds for blood transfusion (November 2016)

An updated systematic review and meta-analysis of randomized trials involving over 12,000 patients has provided more support for the use of a restrictive transfusion strategy (giving less blood, transfusing at a lower hemoglobin level, typically 7 to 8 g/dL) for most hemodynamically stable medical and surgical patients who are not actively bleeding or symptomatic from anemia [24]. An updated 2016 guideline from the AABB (an international organization) also supports the use of restrictive thresholds [25]. The major exception is patients with acute coronary syndromes (ACS), for whom data from large randomized trials are not available and for whom pilot trials suggest a more liberal threshold may be associated with better outcomes. We continue to use an individualized approach to transfusion in patients with ACS. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Society guidelines'.)

Restrictive postoperative transfusion strategy in infants and children with congenital heart disease (October 2016)

In a randomized trial of restrictive versus liberal postoperative transfusion strategies in 162 infants with congenital heart disease undergoing surgical repair or palliation, a restrictive transfusion strategy reduced the red cell transfusion rate, without increasing in-hospital mortality, need for extracorporeal membrane oxygenation (ECMO) support, or hospital length of stay [26]. The restrictive group was transfused for hemoglobin <7.0 g/dL for biventricular repairs or <9.0 g/dL for palliative procedures plus a clinical indication; the liberal group was transfused for hemoglobin <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures. Larger more definitive trials are needed before clear transfusion guidelines in this population can be made. (See "Red blood cell transfusion in infants and children: Indications", section on 'Surgery'.)

Laboratory testing of donated blood for Zika virus (April 2016, Modified August 2016)

The US Food and Drug Administration (FDA) now recommends universal testing of blood components for Zika virus in the United States and its territories (with a several month implementation period), based on an increasing number of cases of mosquito-borne transmission of Zika virus in Florida and Puerto Rico and the potential for sexual transmission from asymptomatic individuals [27]. The testing involves one of two assays that detect Zika virus RNA. Approximately 1 percent of donations from Puerto Rico, an active transmission area, were positive for Zika virus in June of 2016 [28]. Blood collection facilities also use the donor medical and travel history to disqualify individuals who may be infected with Zika virus. (See "Blood donor screening: Laboratory testing", section on 'Zika virus'.)


Unclear role of montelukast in eosinophilic esophagitis (October 2016)

Initial experience suggested that montelukast may be helpful for symptom reduction in patients with eosinophilic esophagitis, but subsequent experience has been mixed. In a small randomized trial, patients with eosinophilic esophagitis were assigned to maintenance treatment with montelukast or placebo for 26 weeks following steroid-induced symptomatic remission [29]. There were no significant differences in the proportion of patients that remained in remission between the two groups. Thus, the role of montelukast in eosinophilic esophagitis, if any, remains unclear. (See "Treatment of eosinophilic esophagitis", section on 'Montelukast'.)

Updated MASCC/ESMO guidelines for nausea and emesis related to cancer treatment (October 2016)

Updated guidelines for prevention and management of cancer therapy-associated nausea and vomiting are available from the Multinational Association of Supportive Care in Cancer and the European Society of Medical Oncology (table 1), the consensus panel also provides guidance on the use of prophylactic antiemetics in patients undergoing radiation therapy. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults", section on 'Recommendations for specific groups'.)

Thrombotic microangiopathy from interferon (October 2016)

Drug-induced thrombotic microangiopathy (DITMA) has been described with a number of chemotherapeutic, immunosuppressive, and other drugs. Unlike thrombotic thrombocytopenic purpura (TTP), DITMA is not associated with severely reduced ADAMTS13 activity, and the principal treatment is drug discontinuation rather than plasma exchange. A new report has provided strong evidence for interferon as a cause of TMA [31]. Patients receiving interferon who develop signs of a TMA should have the drug discontinued promptly before organ failure develops. (See "Drug-induced thrombotic microangiopathy", section on 'Immunosuppressive agents'.)

Complement-mediated HUS, eculizumab, meningococcal group B vaccine, and risk for hemolytic anemia (September 2016)

The introduction of eculizumab (a monoclonal antibody that blocks activation of the terminal complement cascade) has significantly improved the outcome of patients with complement-mediated hemolytic uremic syndrome (HUS), a rare, potentially life-threatening disease. Eculizumab therapy increases the risk of meningococcal infection, and vaccination against Neisseria meningitidis (with a quadrivalent vaccine and, for patients older than 10 years, a serogroup B vaccine) has been recommended in treated patients. However, a review from Health Canada reported an increased risk of hemolytic anemia following receipt of the multicomponent meningococcal serogroup B vaccine (Bexsero, MenB-4C) among patients who were already being treated with eculizumab [32]. To minimize the risk of hemolysis, serogroup B meningococcal vaccination should be performed prior to the initiation of eculizumab therapy, if possible. In cases where prior vaccination is not possible, the manufacturer of eculizumab recommends that serogroup B meningococcal vaccination should be administered when patients are stable and their disease is well controlled and it is assumed that the blood level of eculizumab is high. (See "Complement-mediated hemolytic uremic syndrome", section on 'Adverse effects'.)

Testing for resistance to antiplatelet therapy in patients undergoing coronary stenting (August 2016)

Screening for clopidogrel responsiveness in patients treated with coronary artery stenting has not been shown to improve clinical outcomes. The possible benefit from such screening in patients who are treated with the more potent agent prasugrel was evaluated in the ANTARCTIC study, in which 877 elderly acute coronary syndrome patients who underwent coronary stenting and were treated with prasugrel 5 mg were randomly assigned to platelet function monitoring or no monitoring [33]. There was no difference between the groups in the rate of the primary composite cardiovascular outcome. We do not recommend routine testing of patients for antiplatelet therapy resistance. (See "Clopidogrel resistance and clopidogrel treatment failure", section on 'Screening'.)

Defects in von Willebrand factor function following transcatheter aortic valve replacement (August 2016)

Postprocedural aortic regurgitation (largely paravalvular) develops in approximately 10 to 20 percent of patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) and is associated with worse outcomes, including an increased mortality rate at one year. A study of patients with aortic stenosis undergoing TAVR identified an association between presence of more than mild postprocedural aortic regurgitation and defects in von Willebrand factor function following TAVR [34]. Defects in von Willebrand factor function following TAVR were also associated with mortality risk at one year. While these findings are intriguing, further data are needed to determine the utility of von Willebrand factor testing in patients undergoing TAVR. (See "Transcatheter aortic valve implantation: Overview of complications", section on 'Paravalvular regurgitation'.)

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