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WHAT'S NEW IN COAGULATION: JANUARY 2012

Anticoagulant Monitoring, Dosing Managed By Patients At Home May Be Safe.

Anticoagulant monitoring and dosing managed by patients at home is safe and decreases clotting risk," according to a meta-analysis published online in The Lancet. Investigators found that "major bleeding event and mortality rates actually tended to favor self-management over usual care, although not significantly so (hazard ratios 0.88 and 0.82, both P=0.18)." Meanwhile, "thromboembolic events were nearly halved by self-monitoring (HR 0.51, P=0.01), with even greater benefits in patients younger than 55 and in those with mechanical heart valves. Among older patients, who are at risk for major bleeding, self-monitoring reduced the risk of dying and didn't increase the risk of complications.

Anticoagulant Eliquis (apixaban) Gets FDA Priority Review

U.S. health regulators have assigned priority review to the oral anticoagulant Eliquis (apixaban), a drug shown to be safer and more effective than warfarin in preventing strokes in patients with atrial fibrillation, Bristol-Myers Squibb Co and Pfizer Inc said on Tuesday.The Food and Drug Administration typically takes 10 months or longer to review new drug applications, but could render a decision on Eliquis within six months under an expedited review. The FDA said its goal for a decision is March 28, 2012.

Hormonal Therapy For Prostate Cancer May Be Linked To Higher Blood Clot Risk.

According to a study published in the journal Cancer, prostate cancer patients who undergo hormone-targeted therapy may face an increased risk of developing blood clots. Researchers looked at information on approximately 154,000 older prostate cancer patients. The investigators found that individuals who underwent the hormone therapy had twice the risk of clots compared to patients who did not receive the treatment.

CRP, But Not Platelet Reactivity, Predicts Outcomes Post-PCI

High on-treatment platelet reactivity was not associated with long-term risk of cardiovascular events, but elevated levels of C-reactive protein (CRP) were found to be predictive of worse outcomes independent of other risk factors in a new Korean study in patients receiving drug-eluting stents .

The study, published in the December 13/20, 2011 issue of the Journal of the American College of Cardiology.In an accompanying editorial suggest that, given the CRP results of this study, it may be worthwhile to conduct a trial of intensive statin therapy in patients with elevated CRP following stenting, regardless of LDL level.

They also point out that in the current study, patients with both elevated CRP and high on-treatment platelet reactivity were at the highest risk, which they say raises the question of whether patients with high CRP would benefit the most from platelet-function testing and tailored antiplatelet therapy. "As CRP is a marker of inflammation, it is plausible that patients with elevated CRP would have higher platelet reactivity at baseline, be more likely to exhibit high on-treatment platelet reactivity, and benefit from more potent antiplatelet agents," they write.

In the current study, 2849 patients who had received a drug-eluting stent within the past 24 to 48 hours who were taking clopidogrel underwent platelet-reactivity testing with the VerifyNow assay. Baseline CRP measurements were available in 2546 of the patients. After a median follow-up of 2.2 years, the primary end point--a composite of all-cause death, nonfatal MI, stent thrombosis, and stroke--was not significantly different in those with or without high on-treatment platelet reactivity but was increased in patients with raised CRP.

The VerifyNow platelet test had no incremental usefulness to classify long-term risk, but the incorporation of CRP into a model with conventional clinical and procedural risk factors significantly improved the C-statistic for the prediction of the primary end point (0.729–0.759; p <0.03). "Our study suggests that elevated CRP levels could more accurately identify a high risk for major cardiovascular events in patients receiving drug-eluting stents," the authors conclude.

They note that that their finding of no association of platelet reactivity with long-term risk contrasts with several other studies that have shown a strong association, but they say that because of the relatively small number of events and the clinically low-risk populations involved in such studies, larger-scale clinical trials are needed to confirm whether platelet reactivity is actually a causal factor for clinical events or whether it just acts as a marker of risk.

Cilostazol May Help Improve Platelet Inhibition In CKD Patients.

Adding cilostazol to antiplatelet therapy improves platelet inhibition in patients with chronic kidney disease (CKD) undergoing hemodialysis," according to research published in the American Heart Journal. Investigators found that "the addition of cilostazol to clopidogrel was superior to treatment with clopidogrel alone, even when the maintenance clopidogrel dose was doubled from 75 mg to 150 mg."

FDA Investigating Reports Of Bleeding In Patients Taking Dabigatran Etexilate.

The US Food and Drug Administration (FDA) announced today that it is now investigating postmarketing reports of serious bleeding events in patients taking dabigatran etexilate (Pradaxa, Boehringer Ingelheim)." In a "drug safety communication," the agency said it is "working to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of Pradaxa." HeartWire points out, "Bleeding events with dabigatran have already prompted safety advisories in Japan and Australia and have led to labeling updates in Europe and the US focusing on the need for monitoring renal function.

FDA Panel: Newer Birth Control Medications Should Carry Stronger Safety Warnings.

Medical experts have been taking...[a] look at Drospirenone/Ethinyl Estradiol [Yaz], because of studies that show they may be more likely to cause dangerous blood clots than older versions of the" medication. Chief Medical Editor Dr. Nancy Snyderman said, "Two of the most popular birth control" medications "in use -- Yaz and Yasmin -- were the focus of FDA hearings today about their safety. The majority of the expert panel this evening voted that the labels both for Yaz and Yasmin should have tighter revisions, but not clear yet what those revisions will be. An FDA advisory panel is calling for stronger warnings on the boxes, advising women who take them about those blood clot dangers. Two Food and Drug Administration advisory committees in a joint meeting recommended Thursday that "a popular new generation of birth control" medications "should carry stronger warnings about the risks they pose of potentially life-threatening blood clots. The panel, which voted 21 to 5 in favor of changing the labels, stopped short of recommending that they warn that the drugs are more likely than other contraceptive" medications "to cause blood clots. Instead, the experts suggested that the labels note that the evidence about blood clots is conflicting. The committee "also concluded, by a closer vote of 15 to 11, that the benefits of the" medications "still outweigh their risks." There was concern that the "newer synthetic form of progestin called drospirenone, can make women more prone to blood clots," which "has been a subject of debate."

Studies have shown conflicting evidence about whether women who take the pills have a higher risk of blood clots than if they take older birth control pills that don't contain drospirenone.

Gynecologists Still Plan to Prescribe Newer Birth Control Medications Despite Concerns. Undeterred by evidence that newer birth control" medications "such as Bayer AG's Yasmin may carry more risk of dangerous blood clots, top doctors say they still plan to prescribe them." According to a survey by Bloomberg News, "many clinicians aren't convinced the newer" medications "pose more risk" because "the evidence isn't conclusive or worrisome enough to stop using the" medications.

Preoperative Aspirin May Benefit Patients Undergoing Cardiac Surgery.

Preoperative aspirin therapy was associated with a host of beneficial effects spanning several organ systems, according to a large observational study" published in Annals of Surgery. The researchers wrote, "This study provides new evidence that preoperative aspirin therapy (versus no preoperative aspirin) is associated with a significant decrease in risk of 30 day mortality (3.5% versus 6.5%), renal failure (3.7% versus 7.1%), dialysis required (1.9% versus 3.6%), ICU stay (average 107.2 hours versus 136.1), and a composite outcome -- MACE (8.7% versus 10.8%); and is not associated with increased risk of readmissions (14.5% versus 12.8%)." Additionally, "aspirin was beneficial even though patients taking preoperative aspirin were significantly older and had more comorbidities than those not taking aspirin."

FDA Panel Says Benefits Of Birth Control Patch Outweigh Risks.

The Food and Drug Administration's panel of reproductive health experts voted 19-5 that the benefits of the ethinyl estradiol and norelgestromin transdermal [Ortho Evra] patch outweigh its risks, specifically a potentially higher risk of dangerous blood clots in the legs and lungs." FDA "panelists said the patch can be especially useful for younger women who have difficulty sticking to a daily pill regimen. Despite the safety concerns, the experts stressed that Ortho Evra fills a unique niche among birth-control products."

The panel said, "The agency should change the information label to better reflect the risk.  Women who use the patch have a 55 percent greater chance of experiencing blood clots compared with those who use older low-dose hormonal" medicines, "the agency found in an October study." According to an October report, "the FDA found the incidence of blood clots in women using the patch for one year is 14 in 10,000 women compared with 8 in 10,000 women on older" medications. The Ortho Evra patch...doesn't contain drospirenone, but it contains higher levels of estrogen than found in many common second-generation birth control" medications.

Study Links Aspirin To Reduced Risk Of Recurring Blood Clots.

A study released today at the American Society of Hematology meeting found that "patients who took aspirin daily for two years had a 40 percent reduced risk of clots breaking free and moving in the circulatory system compared with those taking a placebo." The pain reliever could offer "a low-cost therapy after prescribed blood thinners." Giving low-dose aspirin to patients after they've received stronger blood thinners for dangerous clots in the lungs could cut their odds of redeveloping" venous thromboembolisms (VTEs), according to a presentation at the annual meeting of the American Society of Hematology (ASH). HealthDay noted that VTE patients "are typically given anticoagulants such as warfarin (Coumadin)," but extended treatment with such medications bring "an increased risk of bleeding." Commentators on the study called aspirin "a safe and effective alternative to long-term warfarin to reduce the incidence of recurrent venous thromboembolism," but some also noted that aspirin should not "replace the initial treatment of VTE" with "heparin or warfarin anticoagulation 

Everything You Want to Know About Bleeding in AF Patients'

A new executive summary of a consensus document on bleeding risk assessment and management in atrial-fibrillation patients has been made available from the European Heart Rhythm Association The authors of the summary, published in the December 2011 issue of Thrombosis and Haemostasis, say the main aim of the consensus document is to summarize best practice in dealing with bleeding risk in AF patients when approaching antithrombotic therapy. The document reemphasizes all bleeding aspects related to patients taking anticoagulants for AF. "It is a systematic review of the literature looking at risk factors for bleeding, ways to assess these risk factors, and patient values and preferences about the decision to take anticoagulants. AF is the commonest rhythm disorder. It increases the risk of stroke, but we now have effective ways to prevent stroke in these patients with anticoagulants. But these drugs come with a risk of bleeding, so it is important to assess bleeding risk and reduce any risk factors as much as possible. For example, high blood pressure is a risk factor for bleeding. This can be controlled in most patients."

On patient preferences, Lip gave the example of balancing the stroke/bleeding risk. "Most patients say they would rather prevent a stroke at the cost of bleeding, but most doctors are desperate to avoid a major bleed. Stroke is devastating, with a substantial mortality, morbidity, and risk of recurrence. We need to get the balance right."

Some Key Points of the Consensus Document

• In most patients, thromboembolic rates without anticoagulation are markedly (five- to eightfold) higher than bleeding rates. Therefore, most patients with AF--including the majority of patients at high bleeding risk--are in need of anticoagulant therapy.
• The bleeding risk with aspirin should be considered as being similar to that with vitamin-K antagonists, especially in the elderly.
• Most patients with a high CHA₂DS₂-VASc score benefit from oral anticoagulation even if their bleeding risk is high. Only in rare patients with a relatively low stroke risk and an extremely increased risk of bleeding may withholding of oral anticoagulation be considered.
• The HAS-BLED score should be considered as a calculation to assess bleeding risk, whereby a score of >3 indicates high risk, and some caution and regular review is needed following the initiation of antithrombotic therapy, whether with oral anticoagulation or antiplatelet drugs.

There is a section on the new oral anticoagulants. Lip commented: "In a way, these have made the cardiologist's job more difficult. In the days when there was just warfarin, I would make the decision to put a patient on warfarin and then I would refer them to the anticoagulant clinic, which would take over the monitoring and decide whether to change the dose. Now with dabigatran, I have to decide whether to use the high dose or low dose, and for this we need to assess risk of bleeding."

Amikacin Can be Added to Blood to Reduce the Fall in Platelet Count

Our objective was to develop an effective method to prevent the fall in platelet count for patients with anticoagulant-dependent (AD) pseudothrombocytopenia, a spurious phenomenon due to anticoagulant-induced aggregation of platelets. We report a case of insidious multianticoagulant-dependent pseudothrombocytopenia in which AD pseudothrombocytopenia may be caused by 4 anticoagulants, eg, EDTA, sodium citrate, heparin, and sodium fluoride (NaF). Multianticoagulant-dependent pseudothrombocytopenia was confirmed by finding clumped platelets on microscopic evaluation in 4 anticoagulated blood samples. With this case, we tried a variety of reagents, including aminoglycosides, eg, gentamicin and amikacin, vitamin B₆, and aminophylline to inhibit pseudothrombocytopenia. Except for amikacin, all reagents failed to prevent pseudothrombocytopenia. Microscopic examination of K₂-EDTA-, heparin-, sodium citrate–, and NaF-anticoagulated blood samples showed massive platelet clumping, but no aggregate was seen in the anticoagulated blood with amikacin. When amikacin was added within 1 hour after blood sample withdrawal, platelet, WBC, and RBC counts and hemoglobin level, mean corpuscular volume, and mean platelet volume remained unchanged for up to 4 hours at room temperature. These findings suggest that amikacin could inhibit and dissociate pseudo platelet aggregation in multianticoagulant-dependent pseudothrombocytopenia and EDTA-induced pseudothrombocytopenia.

Catheter-Directed Thrombolysis in Iliofemoral DVT Reduces Risk of Postthrombotic Syndrome

Catheter-directed thrombolysis significantly reduced the risk of postthrombotic syndrome (PTS) at 24 months compared with standard therapy in patients with deep vein thrombosis (DVT), according to the results of a new study [1]. The addition of thrombolysis also increased venous patency after six months but was associated with an increased risk of bleeding, including three major and five clinically relevant nonmajor bleeding events.Current guidelines recommend use of anticoagulant therapy, which is really to stop the growth of the thrombus, but it doesn't dissolve the clot. This means that a great number of patients will develop residual vein thrombosis after treatment. Most of the patients will also have damage to the valves, and this over time, probably years, will lead to postthrombotic syndrome, which is characterized by pain, swelling of the leg, cramping, sometimes eczema, and also in some severe cases venous ulcers. Acute DVT of the lower limbs occurs in approximately one person per 1000 individuals per year and is associated with significant morbidity, meaning there are approximately 250 000 to 300 000 affected individuals per year in the US. Treatment with anticoagulation usually involves low-molecular-weight heparin for five to 10 days followed by warfarin for a minimum of three months, although some high-risk patients might receive lifelong anticoagulation. Still, even with adequate anticoagulation and compression stockings for acute proximal DVT, approximately one in four patients are at risk for developing PTS.

Systemic thrombolysis with intravenous streptokinase in the setting of acute DVT has been tested in the past, and while it reduced the risk of PTS, it was associated with significant bleeding complications. In contrast, catheter-directed thrombolysis, which has been used since the 1990s, is a treatment where physicians advance the catheter into the affected vein and through the thrombotic segment. Through multiple side holes in the catheter, alteplase, at a significantly reduced dose, is delivered directly into the clot.

In CAVENT, an open-label study that included 209 patients with a first-time iliofemoral DVT, investigators randomized 108 patients to placebo and 101 patients to catheter-directed thrombolysis within 21 days from symptom onset. After 24 months, 37 patients treated with catheter-directed thrombolysis in addition to anticoagulation developed PTS, compared with 55 patients in the anticoagulation-only control arm (41.1% vs 55.6%; p=0.047). When investigators performed an intention-to-treat analysis, the absolute reduction in PTS events increased from 14.5% to 17.0%. At six months, iliofemoral patency was observed in 58 patients treated with thrombolysis compared with 45 patients in the control arm (65.9% vs 47.4%; p=0.012).

The number-needed-to-treat to reduce one PTS event with catheter-directed thrombolysis was seven, report investigators. The benefits of treatment, however, were offset with an increased risk of bleeding. Overall, 20 patients treated with thrombolysis had a bleeding event, including three major and five clinically relevant nonmajor bleeds. There were no deaths, pulmonary embolisms, or cerebral hemorrhages related to thrombolysis.

Catheter-directed thrombolysis has been around for 20 years but the lack of data supporting its benefit and safety has prevented the therapy from taking off. Data from CAVENT, they state, "will help to preserve limb function in many patients with DVT by reducing the risk of incurable and debilitating postthrombotic syndrome. In addressing the CAVENT study specifically, they point out that 55% of patients in the control arm developed PTS, a number that is too high. The incidence of PTS at two years is high but noted the study included patients with extensive thrombosis in the upper thigh and into the iliac veins. The editorialists suggest that iliofemoral stenting following catheter-directed thrombolysis, a practice widely used in the US, might reduce the high rate of PTS. In CAVENT, 23 patients received angioplasty and 15 received venous stenting.The catheter-directed treatment be performed for one to 1.5 days and should not exceed two days, because a clot that doesn't dissolve within this time frame is likely chronic in nature rather than acute and is unlikely to respond to thrombolysis.

Bleeding Risk Scores Provide Mixed Results, Especially in Intermediate-Risk Patients

Four major bleeding risk scores used in clinical practice identified patient risk differently, with each of the screening tools having a limited ability to predict risks of major bleeding and clinically relevant nonmajor bleeding, according to the results of a new study [1]. Overall, the bleeding risk scores were able to identify patients at high risk for bleeding but had limited ability to identify patients at intermediate risk, report investigators.

There are at least five risk scores that have been published, in populations ranging from patients with thromboembolic disease to those with atrial fibrillation. "Most of the scores, however, have been derived for atrial fibrillation. The most current guidelines suggest that we evaluate patient risk of bleeding before prescribing anticoagulants, but for the last couple of years we've been noticing that the different risk scores classify patients differently." The guidelines recommend using the HAS-BLED or HEMORR₂HAGES risk scores to help guide clinicians about potential risks of bleeding in patients treated with anticoagulant therapy. The risk scores, however, were developed with different methodologies, and while they each emphasize similar risk factors, the weight accorded to each risk factor differs.

In their study, the researchers evaluated the Outpatient Bleeding Risk Index (OBRI), the Contemporary Bleeding Risk Model (CBRM), HAS-BLED, and HEMORR₂HAGES in a retrospective cohort study that included 321 consecutive patients enrolled at a single academic medical center. Of the patients, 57% were male and 72.6% had atrial fibrillation.

Overall, the incidence rates for major bleeding and clinically relevant nonmajor bleeding were 3.7 and 11.2 events/100 patient-years, respectively. The incidence rates differed significantly when assessing bleeding using the four bleeding risk scores, however, with the risk scores identifying 2.6 major bleeding events/100 patient-years using HAS-BLED in intermediate-risk patients to 6.62 major bleeding events/100 patient-years using the CBRM risk score. In intermediate-risk patients, the HAS-BLED score identified 9.07 major and clinically relevant bleeding events/100 patient-years, whereas the CBRM identified 16.12 events/100 patient-years. The predictive ability of each risk score was assessed using the C statistic. For predicting major bleeding, the C statistic for OBRI, CBRM, HEMORR₂HAGES, and HAS-BLED was 0.606, 0.714, 0.735, and 0.672, respectively. For predicting major bleeding and clinically relevant nonmajor bleeding, the C statistic was 0.549, 0.591, 0.613, and 0.587, respectively.

What we found with the four scores is that they all classify patients differently. It really doesn't make any sense if it's the same patient population. Only in the very high-risk categories do we see better performance. The four risk scores all include age, renal function, comorbidities, and a previous history of bleeding.While the scores are intended to be an aid for physicians not at the forefront of anticoagulant management, such as the general practitioner, the differential performance of the four risk scores makes things more difficult. Moreover, in patients it is often hard to predict who bleeds on anticoagulant therapy, given that a lot of events are random, such as accidental falls.

A lot of the variables are actually very easy to assess in clinical practice. The problem with the risk scores is that they try to assign a weight to each variable, and that's what we don't exactly know how to do. When we're prescribing anticoagulants, the patients we're concerned about are the patients with a history of frequent falls, or the elderly patient with cognitive issues. A patient with cognitive issues might have no other risks, but we still might be quite concerned about them."

What's Hot at ASH 2011?

This year's annual meeting of the American Society of Hematology (ASH), which starts next week in San Diego, California, will feature some new drugs, some findings that might breathe new life into an old drug, and also some long-term data that might end a fierce debate.

"We are really building on the foundation of high-throughput genomic sequencing and the discovery of new targets for the development of new drugs," said ASH president J. Evan Sadler, MD, PhD, professor of medicine in the division of hematology at Washington University, in St. Louis, Missouri. "We have, on the one hand, new targeted therapies; on the other hand, we have so much information about individual patients that we can say which targeted therapies may be specifically useful for them."

Speaking at a premeeting conference call with journalists, Dr. Sadler highlighted several abstracts as being particularly newsworthy.

One of the new targeted therapies that holds great promise, although the research is still in the early stages, is the first drug that has been designed to home in on Bruton's tyrosine kinase, he noted. This enzyme plays a central role in B cell development, and has been implicated in chronic lymphocytic leukemia. The new drug, currently known as PCI-32765 (Pharmacyclics), is an oral irreversible inhibitor of the enzyme. The results of a phase 2 study of 61 patients suggest efficacy, and will be presented at the meeting (abstract 983). A larger phase 3 study is now planned.

"I don't want to hype this, but we are hoping for a repeat of the success that was enjoyed by the poster child of targeted therapy, imatanib (Gleevec), for the treatment of chronic myeloid leukemia," Dr. Sadler said. Subsequent tyrosine kinase inhibitors have not shown such spectacular results, he noted, "but this one looks encouraging. There have been some striking responses described."

"This is the way of the future, where scientists first understand the molecular defect of the disease, and then drugs are designed to specifically target those diseases," explained ASH secretary and coordinator of the abstracts review, Charles Abrams, MD, associate chief of the division of hematology/oncology at the University of Pennsylvania in Philadelphia. The defect of Bruton's tyrosine kinase was first identified in children with an inherited blood disorder, X-gammaglobulinemia; this story goes "all the way from the patient to the laboratory bench and then back to the patient," he said.

Another example of how observations in patients have resulted in new therapies is that of thalidomide and related drugs, said Dr. Sadler. Studies of how thalidomide produced birth defects led to its use in the treatment of multiple myeloma, and resulted in the development of related next-generation agents, such as lenalidomide (Revlimid, Celgene) and the investigational agent pomalidomide (under development by Celgene). Exactly how these drugs exert their antitumor effects has been unclear. New research to be presented at the meeting (abstract 127) outlines the central role played by the recently identified protein cereblon. It appears to be "absolutely required" for a response to these drugs, say the authors, and preliminary data suggest that low levels of cereblon in a patient with multiple myeloma predicts a poor response to these drugs.

Breathing New Life Into an Old Drug

Featured in the plenary session will be research that could breathe fresh life into an old drug — gemtuzumab (Mylotarg, Wyeth) (abstract 6). This product was voluntarily withdrawn from the American market last year. It had been available for a decade, after the US Food and Drug Administration (FDA) granted it accelerated approval in 2000 for the treatment of relapsed acute myeloid leukemia (AML). However, subsequent clinical trials and years of postmarketing experience did not show evidence of clinical benefit in patients with AML, according to the FDA, and revealed toxicity that was highlighted in a black box warning.

Gemtuzumab is a monoclonal antibody directed against CD33 on white blood cells; it was used to supplement the treatment of AML, particularly in older patients, Dr. Abrams explained. It was then tested in the initial treatment of AML, but the results were inconclusive and some alarming toxicities emerged, he said. "In one trial in younger patients, mortality actually increased in patients who received the drug," he explained, so the drug was withdrawn.

In the study to be presented, gemtuzumab was used upfront in older patients, around 60 to 70 years of age, who were newly diagnosed with AML. The results show that "not only was there a benefit in the initial treatment of the disease, there was also a survival benefit," Dr. Abrams explained. "This study is really quite tantalizing," he said. There will now be a resurgence of interest in gemtuzumab, he predicted, adding that "this is a drug that wasn't studied fully enough."

Novel Cell-Based Approach

A novel cell-based approach to therapy is highlighted in a study in which genetic engineering was used to program some lymphocytes to attack other lymphocytes (abstract 167), noted Dr. Sadler. "This is instructing the T cells in what they should attack, rather than leaving it up to our immune system," he added. In this research, T cells were genetically engineered to express chimeric antigen receptors that specifically recognize the B cell antigen CD19, and were tested in patients with B cell malignancies. The clinical trial has so far enrolled 4 patients with chronic lymphocytic leukemia and 4 with B cell lymphoma.

Stem-cell transplantation offers a curative therapy for some hematologic malignancies, and a whole press conference at the meeting will focus on developments in this approach. One abstract describes an emerging methodology for preventing chronic graft-vs-host disease (GvHD) (abstract 817); another reports an increased incidence of chronic GvHD and no survival advantage with peripheral blood stem cells, compared with bone marrow transplantation (abstract 1). In addition, there are now long-term data (10+ years) on survivors of hematopoietic cell transplantation (abstract 841).

Answer to Longstanding Question?

An answer to a longstanding question about how best to treat patients with limited-stage Hodgkin's lymphoma comes from a final analysis of a trial now with a median follow-up of 11.3 years (abstract 590). There has been fierce debate about whether the initial treatment of these patients should include radiotherapy or whether they should be treated with chemotherapy alone; proponents of chemotherapy alone argue that adding radiation increases the risk for late toxicities without providing any clear benefit.

However, when radiotherapy was added to chemotherapy, the short-term results do look better, said Dr. Sadler. "Now, looking at the very long-term data, the morbidity and mortality associated with late complications from radiotherapy may well trump this short-term effectiveness," he added.

"I interpret this study as evidence that the long-term complications of radiotherapy are not necessarily worth the short-term efficacy," Dr. Sadler said. It appears that treating initially with chemotherapy alone will give sufficient benefit; if the patient relapses, they can be given radiotherapy, he explained. This approach would spare a number of people the toxicity of radiation, he noted. Dr. Abrams added that this is a very well-designed study with very long-term follow-up. In answer to the question of whether this is a final answer, he said: "I doubt that there will be another trial like this."

Other Hematology News

In addition to news on the hematologic malignancies front, which we will be focusing on here at Medscape Medical News, other newsworthy abstracts to be presented include a new gene therapy for hemophilia B (abstract 5), and research on the use of antiplatelet agents to decrease the recurrence of venous thromboembolism (abstract 543).

Several presentations will focus on sickle-cell disease, which is a fairly common and at times a morbid condition, said Dr. Abrams. It has long been known that these patients have a mutation in hemoglobin, but although they all have the same mutation, some patients have relatively mild disease and others have severe forms and die in childhood. "It has always been extremely perplexing as to why," he said. Metabolomic studies that have looked beyond hemoglobin are starting to provide some answers for the variability in this disease (abstract LBA-3).

Hydroxyurea is a standard treatment for sickle cell disease, but there has always been some discomfort about using such chemotherapy, particularly in children, Dr. Abrams noted. However, a large trial of children provides reassuring data on the safety and efficacy of hydroxyurea in the pediatric population (abstract 7 and abstract 8), which is "good news for our patients," he said. Another trial highlighted in the press program explores the use of preoperative blood transfusions to prevent complications in patients with sickle cell disease who undergo low- or moderate-risk surgery (abstract 9).

Heparin-Compromised Patients May Be Safely Treated With Newer Anticoagulants.

Heparin-compromised patients can be safely treated with the newer anticoagulants, including dabigatran (Pradaxa, Boehringer Ingelheim), apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), and rivaroxaban (Xarelto, Bayer/Johnson & Johnson), suggest the results from a new laboratory analysis." These "new agents did not interact with heparin-induced thrombocytopenia (HIT) antibodies, which suggest they are an anticoagulation option for patients unable to take heparin." The research was presented at the American Society of Hematology 2011 Annual Meeting.

Donna Castellone

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Donna Castellone,
MS, MT(ASCP)SH
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