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What's new in hematology
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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: Jan 2017. | This topic last updated: Feb 21, 2017.

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 LEUKEMIA AND MYELODYSPLASTIC SYNDROME

2017 European LeukemiaNet (ELN) prognostic stratification scheme for AML (February 2017)

Cytogenetic and molecular features of acute myelogenous leukemia (AML) permit stratification of patients into various prognostic groups. We prefer the classification system recently updated by the European LeukemiaNet (ELN) (table 1) [1]. This revised schema distinguishes three prognostic categories and incorporates data on additional gene mutations (eg, TP53, ASXL1), biallelic mutated CEBPA, the allelic ratio of FLT3-ITD, and effects of specific combinations of such features. These prognostic variables, coupled with the patient's clinical status, often inform key therapeutic decisions regarding management of AML. (See "Prognosis of acute myeloid leukemia", section on 'European LeukemiaNet classification' and "Post-remission therapy for acute myeloid leukemia in younger adults" and "Treatment of relapsed or refractory acute myeloid leukemia".)

ANEMIA AND OTHER RED CELL DISORDERS

Rapidly progressive acute chest syndrome in sickle cell disease (February 2017)

Acute chest syndrome (ACS) in individuals with sickle cell disease (SCD) encompasses a variety of clinical presentations and severities. A distinct phenotype of ACS has been characterized, referred to as rapidly progressive ACS, in which respiratory failure occurs within 24 hours of initial respiratory symptoms [2]. In a cohort of 97 children and 76 adults with SCD and at least one prior ACS episode, rapidly progressive ACS occurred more commonly in adults than children (21 versus 2 percent). Adults with rapidly progressive ACS were more likely to have multiorgan failure compared with adults without this phenotype. The only laboratory predictor of rapidly progressive ACS was a decline in platelet count on presentation. (See "Evaluation of acute pain in sickle cell disease", section on 'Acute systemic illness, diffuse pain, or both'.)

Crizanlizumab for sickle cell pain episodes (December 2016)

Crizanlizumab is an investigational monoclonal antibody directed against P-selectin, an adhesion molecule that contributes to vasoocclusive pain in individuals with sickle cell disease (SCD). In a randomized trial in patients with SCD that compared two different doses of crizanlizumab and placebo, administered intravenously every four weeks over a year, vasoocclusive pain episodes decreased by about 50 percent (1.6 versus 3 events annually) in the higher-dose crizanlizumab group compared with placebo [3]. The benefit persisted regardless of the baseline frequency of painful events, SCD genotype, and concomitant hydroxyurea use. This agent, which is not yet clinically available, will likely be the first new disease-modifying agent for SCD since hydroxyurea was introduced as a therapy for SCD almost two decades ago. (See "Vasoocclusive pain management in sickle cell disease".)

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 [4]. 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'.)

CHRONIC LEUKEMIAS AND THE MYELOPROLIFERATIVE NEOPLASMS

Ibrutinib and Pneumocystis pneumonia (December 2016)

The Bruton tyrosine kinase inhibitor ibrutinib has not clearly been associated with an increased risk of opportunistic infections, but cases have been reported. In a series of 96 patients receiving ibrutinib as the sole agent for chronic lymphocytic leukemia (CLL), five were reported to have Pneumocystis pneumonia [5]. All of the infections were grade ≤2 and resolved with oral trimethoprim-sulfamethoxazole. A limitation is that the diagnoses were made by polymerase chain reaction (PCR) of bronchoalveolar lavage fluid, which could represent a false positive in the setting of colonization with Pneumocystis. Nevertheless, clinicians should have a high index of suspicion for Pneumocystis pneumonia in patients receiving ibrutinib, and the diagnosis should be sought in those with compatible signs and symptoms. (See "Risk of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib' and "Prevention of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib and idelalisib'.)

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 [6]. 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'.)

HEMATOPOIETIC CELL TRANSPLANTATION

Molecular markers of prognosis following transplant in myelodysplastic syndromes (February 2017)

Although allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelodysplastic syndromes (MDS), controversy surrounds selection of candidates, given the associated risks. In a retrospective study of over 1500 patients who underwent HCT for MDS, those whose biopsies revealed TP53 mutations experienced shorter overall survival, regardless of whether they underwent myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) [7]. In contrast, those with RAS pathway mutations experienced worsened survival only if they received RIC. This analysis suggests that molecular features may increasingly aid in selection of candidates for HCT and influence the choice of conditioning regimen in MDS. (See "Hematopoietic cell transplantation in myelodysplastic syndromes", section on 'Cytogenetic and molecular factors'.)

Palliative care during hematopoietic cell transplantation (February 2017)

For patients with serious life-threatening illness, comprehensive palliative care can be successfully integrated with disease-modifying treatment. The benefits of delivering palliative care alongside potentially curative treatment were shown in a randomized trial of inpatient palliative care consultation versus usual transplant care in 160 adults with hematologic malignancies undergoing autologous or allogeneic hematopoietic cell transplantation [8]. At two weeks posttransplant, the increase in depression, anxiety, and overall symptom burden was less in the intervention group, and the decrease in quality of life (QOL) was also smaller. Depression and QOL benefits persisted at three months. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)

Association of vitiligo with hematopoietic stem cell transplantation (February 2017)

Previous reports suggested that recipients of hematopoietic stem cell transplantation (HSCT) have an increased risk of developing vitiligo. In a Korean nationwide population study including approximately 2700 HSCT recipients and 8200 controls, HSCT recipients had a threefold increased risk of developing vitiligo [9]. Risk factors included receipt of an allogeneic versus autologous graft and stem cells derived from the bone marrow rather than peripheral blood. Although the pathogenetic mechanisms underlying the development of vitiligo in HSCT recipients are unclear, they may include adoptive transfer of vitiligo from donor, immunosuppression associated with preparative regimens, or chronic graft-versus-host disease. Clinicians should counsel patients undergoing HSCT regarding the risk of vitiligo. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis", section on 'Etiology'.)

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 [10]. 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'.)

HEMOSTASIS AND THROMBOSIS

Underdosing of direct oral anticoagulants (February 2017)

The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban (collectively called direct oral anticoagulants [DOACs]) have been available for several years. A real-world study of over 1500 patients with venous thromboembolism (VTE) who were treated with a DOAC found that dosing differed from the recommended product dosing in 20 to 50 percent of cases, depending on the agent [11]. These deviations (mostly underdosing) correlated with an increased frequency of VTE recurrence. Clinicians should familiarize themselves with prescribing information to avoid adverse outcomes. (See "Direct oral anticoagulants: Dosing and adverse effects", section on 'Clinician familiarity with dosing'.)

Dabigatran combined with certain statins associated with increased risk of major bleeding (February 2017)

An analysis of health records of nearly 46,000 Canadian patients showed that older adults (age ≥66) with atrial fibrillation taking dabigatran who also received simvastatin or lovastatin had approximately a 50 percent greater risk of hospitalization for major hemorrhage relative to those who used other statins [12]. Although the mechanism for this interaction is uncertain, until additional information becomes available, it may be prudent to choose a statin other than lovastatin or simvastatin for older patients receiving dabigatran, and for those with an elevated risk for serious bleeding. (See "Statins: Actions, side effects, and administration", section on 'Drug interactions'.)

Anticoagulant thromboprophylaxis not warranted in nonmajor lower limb orthopedic surgery (January 2017)

Whether anticoagulation thromboprophylaxis is indicated for patients with lower leg immobilization from below knee casting or undergoing arthroscopy was evaluated in a randomized trial [13]. The rate of symptomatic venous thromboembolism (VTE) was low (<2 percent) and not affected by the administration of anticoagulant prophylaxis. Risk factors in addition to the surgery itself were present among the few patients who did develop thrombus. This trial supports the current recommendation that, for patients with lower leg immobilization due to below knee casting or arthroscopy who do not have additional risk factors for VTE, anticoagulant prophylaxis is not warranted. (See "Prevention of venous thromboembolic disease in surgical patients", section on 'Orthopedic surgery'.)

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 [14]. 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 among patients with syncope who are admitted to the hospital. The prevalence of diagnosed PE was lower (4 percent) when looking at all patients seen in the emergency department with syncope, although the total number of these patients who were assessed for PE was not reported. (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]) [15]. 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 [16]. 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'.)

LYMPHOMA: HODGKIN AND NON-HODGKIN

Ibrutinib in marginal zone lymphoma (January 2017)

Treatment of nodal marginal zone lymphoma (MZL) has been based on retrospective studies and extrapolation from trials in follicular lymphoma. In preliminary results of an open-label, single arm phase 2 trial, half of patients with relapsed MZL after anti-CD20-based treatment responded to ibrutinib [17]. These higher-than-expected response rates led to accelerated approval by the US Food and Drug Administration for use of ibrutinib in this MZL population. Given these findings, ibrutinib is an additional option for patients with MZL who have relapsed after anti-CD20-based treatment, though further study is needed to determine if it will improve survival. (See "Treatment of marginal zone (MALT) lymphoma", section on 'Treatment'.)

Obinutuzumab-based regimens for previously untreated follicular lymphoma (December 2016)

Preliminary results from an international, open-label, randomized phase III trial comparing an obinutuzumab-based induction and maintenance strategy versus a rituximab-based strategy in 1202 patients with previously untreated advanced- stage follicular lymphoma have been presented in abstract form [18]. At a median follow-up of 35 months, the obinutuzumab-based strategy resulted in deeper responses and superior progression-free survival. It is not known whether this will translate into an overall survival benefit with longer follow-up. While we generally prefer rituximab-based regimens, these results suggest that obinutuzumab-based regimens are an acceptable alternative for the initial treatment of advanced-stage follicular lymphoma. (See "Initial treatment of advanced stage (III/IV) follicular lymphoma", section on 'Choice of anti-CD20 antibody'.)

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 [19]. 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'.)

MULTIPLE MYELOMA AND OTHER PLASMA CELL DISORDERS

Bortezomib, lenalidomide, dexamethasone for previously untreated multiple myeloma (December 2016)

Until now, published data regarding bortezomib, lenalidomide, and dexamethasone (VRd) in previously untreated multiple myeloma (MM) was limited to phase 2 trials. In a multicenter phase 3 trial (SWOG S0777), 525 patients with previously untreated MM were randomly assigned to receive six months of induction therapy with either VRd or Rd, each followed by Rd maintenance until progression or unacceptable toxicity [20]. VRd resulted in higher response rates and improved both progression-free and overall survival. This supports our preference for VRd as the initial treatment of most patients with standard-risk MM. Given that VRd is associated with greater toxicity, Rd is an acceptable alternative for frail adults, especially those with preexisting neuropathy, and patients age 75 years or older who are expected to have higher rates of toxicity with VRd. (See "Selection of initial chemotherapy for symptomatic multiple myeloma", section on 'Bortezomib, lenalidomide, dexamethasone (VRd)'.)

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

Screening donated blood for babesiosis in the United States (December 2016)

Naturally occurring Babesia microti infection within the United States is regionally distributed, with high-risk areas located in the Northeast and upper Midwest. In an analysis of almost 90,000 blood donations from four states in these regions, 335 (0.38 percent) were found to be positive for B. microti using a DNA-based or antibody-based test [23]. Screening of donated units was found to be effective in preventing transmission. Testing blood donations for B. microti is not mandatory in the US, but many units collected in high-risk regions are being screened. (See "Blood donor screening: Laboratory testing", section on 'Babesia microti'.)

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 [24]. 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 [25]. An updated 2016 guideline from the AABB (an international organization) also supports the use of restrictive thresholds [26]. 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 [27]. 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'.)

OTHER HEMATOLOGY

Masitinib in indolent and smoldering systemic mastocytosis (February 2017)

There are limited treatment options for indolent (ISM) and smoldering (SSM) forms of systemic mastocytosis. Masitinib is a tyrosine kinase with activity against at least three mast cell signaling molecules. In a phase III trial of 135 severely symptomatic patients with ISM or SSM, oral masitinib reduced symptoms, tryptase levels, and urticaria pigmentosa lesions compared with placebo, although 24 percent of patients receiving masitinib had side effects requiring discontinuation [28]. The drug is under regulatory review, and further data about the safety and efficacy are needed before its use can be recommended. (See "Systemic mastocytosis: Management and prognosis", section on 'Clinical trials'.)

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 2), 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'.)

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