NEJM Group Announces the Launch of NEJM Knowledge+

Posted by Karen Buckley • April 17th, 2014

NEJM Group is excited to announce the launch of NEJM Knowledge+ Internal Medicine Board Review, a self-assessment and continuous learning solution that employs the very latest adaptive learning technologies to increase learning efficiency and knowledge retention.

Designed specifically for Internal Medicine and Internal Medicine subspecialists, the product includes:

  • Over 4000 questions covering nearly 1500 key learning points
  • Two timed practice exams that simulate the actual board exam
  • Desktop, iPad, and iPhone access – wherever and whenever it’s convenient for you
  • Opportunity to earn 250 AMA PRA Category 1 CME Creditstm
  • Opportunity to earn 80 ABIM MOC points which also satisfy the new ABIM patient safety requirement (Medical Knowledge points)
  • Robust, multi-faceted progress and performance reporting

We partnered with Area9 — a physician-led pioneer in adaptive learning — to create this first-of-its-kind platform with smart technology that actually continuously assesses your knowledge, study habits, and schedule, selecting from thousands of learning opportunities and presenting just what you need to become fully prepared. NEJM Knowledge+ presents questions based on what you know already, what you need to study more, what you are struggling to master, what you think you know better than you do, and what you might be forgetting .  For a fun and informative look at how we’ve used adaptive learning check out our animated video.

NEJM Knowledge+ is planned as a family of products to support self-assessment, learning, and board certification in internal medicine and other specialties.  Future review products in other specialties will all be designed to help clinicians efficiently self-assess their learning needs, meet their certification requirements, prepare for the board exams, and incorporate lifelong learning into their schedules more easily.

To learn more about NEJM Knowledge+ visit You’ll find lots of great information, videos, our question of the week, blog, and more.

To take advantage of our Charter Offer and receive a 20% discount on NEJM Knowledge+ Internal Medicine Board Review click here.

The Massachusetts Medical Society designates this enduring CME activity for a maximum of 250 AMA PRA Category 1 Credits™. Physicians should claim only credit commensurate with the extent of their participation in the activity.
NEJM Knowledge+ Internal Medicine Board Review has been accepted by the American Board of Internal Medicine for 80 points toward the Self-Evaluation of Medical Knowledge (Part 2) requirement of Maintenance of Certification (MOC).

Ledipasvir–Sofosbuvir for Previously Treated HCV

Posted by Carla Rothaus • April 16th, 2014

The old adage, “The more things change, the more they stay the same,” simply does not apply when it comes to the treatment of hepatitis C virus (HCV). The mainstay of HCV treatment for many years has included interferon (peginterferon, since 2001) and ribavirin. While relatively effective for patients with HCV genotypes 2 and 3, this regimen achieves a sustained virologic response – undetectable serum HCV RNA after treatment – in only 40% of patients with HCV genotype 1, the cause of more than 70% of all cases of chronic HCV in the United States.  Sequencing of the viral genome and characterization of HCV proteins led to development of the direct-acting HCV NS3/4A protease inhibitors telaprevir and boceprevir, which, when combined with peginterferon and ribavirin, improve response rates for patients with genotype 1. Yet patients who fail this regimen have historically had no treatment options. Now, however, a new generation of direct-acting antivirals is poised to take center stage, changing the outlook for this and other “difficult-to-treat” subgroups. Currently approved regimens – limited by formidable side effects, suboptimal treatment adherence, and viral resistance, and unavailable to those for whom interferon is contraindicated – will likely give way to safer, shorter duration, and easier-to-administer interferon- and ribavirin-free regimens. A multitude of clinical trials are underway, investigating these new therapies in a variety of clinical settings.

In this week’s NEJM, Afdhal et al. report the findings of a study involving patients with HCV genotype 1 who have failed treatment with prior interferon-based therapy. Building upon promising phase 2 trial results, they conducted a multicenter phase 3, randomized, open-label study of a fixed dose, once-daily oral combination pill containing sofosbuvir, a nucleotide analogue HCV NS5B polymerase inhibitor approved by the FDA in late 2013, and ledipasvir, a new experimental HCV NS5A protein inhibitor. Eligibility criteria included age 18 years or older, chronic HCV genotype 1 infection, and failure to achieve a sustained virologic response to prior peginterferon and ribavirin treatment, either with or without a protease inhibitor. Four hundred and forty patients, all of whom received the same daily dose of sofosbuvir and ledipasvir, were randomized 1:1:1:1 to one of four treatment groups, including ledipasvir-sofosbuvir for 12 weeks or 24 weeks, either with or without ribavirin. Randomization was stratified by genotype (1a or 1b), prior treatment response (no response versus relapse or virologic breakthrough) and presence or absence of cirrhosis. The primary endpoint was the rate of sustained virologic response at 12 weeks after the end of therapy (SVR 12); SVR 24 was a secondary endpoint.

The study results showed high SVR 12 rates in all four groups, reportedly among the highest to date for HCV genotype 1: 94% and 96% for the 12 week groups without and with ribavirin, respectively, and 99% for both 24 week groups. Virologic relapse after the end of treatment occurred in 11 of 440 patients (2%), all from the 12 week treatment groups. All sustained virologic responses achieved at 12 weeks persisted at 24 weeks after the end of treatment. Ribavirin did not affect response rates with either 12 or 24 weeks of treatment. In the 12-week group only, response rates were slightly lower in patients with cirrhosis, compared to those without cirrhosis, although the study was not powered to allow confident intergroup comparisons. Mild to moderate adverse events were seen in all groups, with serious adverse events limited to a small number of patients in the 24-week groups; no participant had to discontinue treatment due to an adverse event.

In an accompanying editorial, Drs. Jay Hoofnagle and Averell Sherker of the National Institutes of Health characterize the study results as “striking,” stating that the availability of safe and effective oral therapies will remove most of the limitations and barriers to treatment. Their enthusiasm is tempered, however, by concerns about the high price tag for these therapies, saying, “Costs alone cast a pall over the stunning success in achieving the long-hoped-for goal of a well-tolerated and successful therapy for hepatitis C.”

NEJM Deputy Editor Dr. Mary Beth Hamel adds, “The recent development of several novel direct-acting antivirals represents a major advance in hepatitis C therapy, and offers the potential to save many lives.”

Test Yourself! Interactive Medical Case Now Available

Posted by Jennifer Zeis • April 15th, 2014

A 65-year-old woman presented to an urgent care clinic with a 1-week history of fatigue, dyspnea on exertion, and daily fevers of up to 38.9°C. She reported no chills but did have night sweats. She had difficulty breathing, especially when climbing stairs and when attempting to sleep while lying supine. She had no cough, sore throat, chest pain, edema of the legs, rash, or gastrointestinal symptoms.

The latest Interactive Medical Case, A Woman with Fever and Dyspnea, is now available for you to test your therapeutic and diagnostic skills. In addition, you may now earn two ABIM Maintenance of Certification (MOC) points for each case you take.

Interactive Medical Cases are online simulations based on a real patient’s experience of illness. You follow interactive steps through an evolving patient’s history, diagnosis, and management, from presentation to outcome. During the presentation of the case, you access videos, lab results and brief commentary that explain concepts important for diagnosis and treatment.

Browse the list of Interactive Medical Cases. Try one or all 29 cases and earn points toward your requirements now!

Take the Case Challenge

Posted by Jennifer Zeis • April 13th, 2014

Peripheral-Blood Smear (Wright–Giemsa stain)

A 59-year-old man was seen in an outpatient clinic because of fatigue, abdominal pain, anemia, arthralgias, and abnormal liver function. What is the diagnosis? Is it alcohol-induced sideroblastic anemia? Lead poisoning? Or something else?

Read the case description for the next Case Record of the Massachusetts General Hospital, and then vote and comment now on In a few days, find the answer in the full text of the Case Record to be published April 17.

Follow the conversation with #NEJMCases on Twitter or Facebook.

Hypersensitivity to Hymenoptera Stings

Posted by Sara Fazio • April 12th, 2014

Anaphylactic reactions after a hymenoptera sting should be treated promptly with intramuscular epinephrine. Patients who have had such a reaction should carry injectable epinephrine and be referred to an allergist for insect-specific testing and subcutaneous immunotherapy if indicated.  The latest Clinical Practice review on this topic comes from the University of South Florida Morsani College of Medicine’s Dr. Thomas B. Casale and the University of North Carolina at Chapel Hill School of Medicine’s Dr. A. Wesley Burks.

Although anaphylaxis due to an insect bite has been reported in a small number of cases, stings from insects belonging to the order Hymenoptera are among the most important causes of systemic allergic reactions.

Clinical Pearls

What is the antigentic cross-reactivity between Hymenoptera species?

The Hymenoptera insects whose stings cause allergy are generally from three families: Apidae (honeybees and bumblebees), Vespidae (hornets, wasps, and yellow jackets), and Formicidae (fire ants). The molecular characteristics of the venoms from the three families of Hymenoptera are sufficiently different that there is very little antigenic cross-reactivity. Within families (e.g., vespids), there can be substantial cross-reactivity among the allergens present in the venoms; however, honeybee and bumblebee allergies are distinct.

Table 1. Characteristics of Hymenoptera.

Figure 1. Hymenoptera.

What is the pathophysiology of an allergic reaction to a Hymenoptera sting, and how common is an anaphylactic reaction?

In sensitized persons, a sting can cause the injected venom to bind to venom-specific IgE on mast cells, cross-linking high-affinity IgE receptors and subsequently leading to the rapid release of mast-cell mediators, including histamine, leukotrienes, prostaglandins, and platelet-activating factor. The released mast-cell mediators can cause a spectrum of allergic reactions, from local reactions (affecting small or large [greater than or equal to 10 cm] areas) or urticaria to anaphylaxis and even death. Patients with large local reactions usually do not have a systemic reaction to subsequent stings (with systemic reactions occurring in <10% of these patients), nor do children with isolated urticaria. However, a previous systemic reaction in a patient with venom-specific IgE is associated with a high risk of subsequent systemic reaction, which may occur in 30 to 60% of these patients. Anaphylaxis due to a hymenoptera sting causes at least 40 deaths per year in the United States, although this number is probably an underestimate. Severe systemic allergic reactions occur in approximately 0.4 to 0.8% of children and 3.0% of adults.

Morning Report Questions

Q: What are the risk factors for a severe reaction to a Hymenoptera sting and how should it be treated?

A: Acute systemic reactions typically occur very rapidly after a hymenoptera sting but may be delayed for several hours or be biphasic. The factors associated with an increased risk of severe reaction include being stung by a honeybee (greater risk than with other hymenoptera), underlying mast-cell disorders with elevated serum-tryptase levels at baseline, a previous severe reaction, preexisting cardiovascular disease, and concomitant treatment with a beta-blocker, angiotensin-converting-enzyme inhibitor, or both. Anaphylaxis can present with a spectrum of signs and symptoms affecting multiple organ systems, including the skin, gastrointestinal tract, cardiovascular system, nervous system, and both the upper and lower respiratory tracts; hallmarks of anaphylaxis are the development of hypotension or the involvement of more than one organ system. The treatment of anaphylaxis in the emergency department should include epinephrine for any patient who has more than cutaneous symptoms; epinephrine should also be considered in adults with urticaria alone. H1-antihistamines can help relieve cutaneous signs and symptoms. For respiratory symptoms, supplemental oxygen and inhaled beta2-agonists should be used. For patients with hypotension, volume resuscitation is indicated, with 1 to 2 liters of 0.9% (isotonic) saline infused rapidly (e.g., a dose of 5 to 10 ml per kilogram in the first 5 to 10 minutes in an adult, and 10 ml per kilogram in a child).

Table 2. Clinical Features of Anaphylaxis.

Q: Who should receive venom immunotherapy?

A: Subcutaneous immunotherapy should be considered in all patients who have had a systemic allergic reaction to an insect sting and who have a positive skin test or a positive result on an in vitro test for venom-specific IgE antibodies. Children 16 years of age or younger who have had isolated cutaneous systemic reactions to insect stings have a very low risk of subsequent reactions and do not require venom immunotherapy. Venom immunotherapy is also generally not necessary in patients who have had only a large local reaction, because their risk of subsequent systemic reactions is relatively low. However, patients with unavoidable or frequent exposures (e.g., beekeepers) may benefit, because observational data indicate that, after immunotherapy, local reactions are reduced in size and duration.

Table 3. Criteria for Positive Skin Tests.

Traumatic Injuries after a Bomb Explosion

Posted by Sara Fazio • April 12th, 2014

In this week’s Case Record of the Massachusetts General Hospital, a 34-year-old man was brought to the emergency department because of injuries sustained when a bomb exploded at the Boston Marathon. His right leg had been amputated below the knee and his left leg was burned. Imaging showed metallic foreign bodies in the legs, pelvis, and chest.

A new measure of the medical response to an event such as this is called critical mortality rate in blast injuries. This number excludes people who die at the scene and considers the proportion of those who reach hospitals and then subsequently die. The critical mortality rate after the Boston Marathon bombing was less than 1%.

Clinical Pearls

What are the important considerations in tourniquet application at the scene of an injury?

Application of a tourniquet for up to 1 hour seems to be safe, and even a period of up to 2 hours is associated with low morbidity. More than the complications related to aggressive use, the major concern lies with the inadequate control of bleeding due to inadequate tightening, inappropriate placement, or suboptimal tourniquet design. The major risk is that a tourniquet, if not tight enough, can exacerbate bleeding because it stops venous return without stopping arterial output. Although it is possible to improvise an effective arterial tourniquet, it requires a windlass or other device to create leverage. The problem is that most people don’t know how to do that. Simply knotting a shirt around a limb is universally ineffective. One doesn’t want to discourage bystanders from helping the injured, but probably the best thing an untrained bystander can do for a traumatic amputation is pack the wound tightly.

How are blast injuries categorized?

Primary blast injuries result from increased pressure (e.g., bilateral perforated tympanic membranes). Secondary blast injuries result from projectiles from the explosive device (e.g., traumatic limb amputation). Tertiary blast injuries are due to collision with adjacent objects, and quaternary injuries result from other effects (e.g., thermal injury).

Morning Report Questions

Q: What are important features of early rehabilitation to a trauma patient in the intensive care unit?

A: Early rehabilitation improves functional mobility of patients in the intensive care unit and helps prevent ICU-acquired muscle weakness. Components of early rehabilitation include daily titration of sedation and opioids to allow for spontaneous breathing on the ventilator and early extubation. Subsequently, it is important to implement goal-directed early-mobilization therapy in collaboration with physical therapy and rehabilitation services. Orchestration of multidisciplinary critical care medicine is a key component of an intensivist’s responsibilities. Evaluation by the trauma psychiatry service is important to uncover acute psychiatric issues, in association with optimization of pain symptoms and sleep in order to prevent a post-traumatic stress disorder. Long-term epidural analgesia (tunneled catheter) with local anesthetics may be required to achieve acceptable control of pain and minimize opioid-therapy associated side effects. Positioning and exercise training are important to preserve joint range of motion and muscle length. As a patient improves, physical therapy may progress to include a focus on aerobic exercise and functional mobility training. In family-centered critical care medicine, the strengths and needs of all family members are considered.

Q: What are the increased metabolic requirements associated with a unilateral below-the-knee amputation (BKA) or a unilateral above-the-knee amputation (AKA)?

A: When coordinating early mobilization in the surgical ICU, one needs to consider that traumatic lower limb amputations increase the metabolic demand on the body. A unilateral BKA results in roughly a 25% increased energy expenditure for ambulation beyond a person’s preamputation level; with unilateral AKA this same person can expect about a 60% increased energy expenditure.

Fibrinolysis for Acute Intermediate-Risk Pulmonary Embolism

Posted by Gelareh Homayounfar • April 10th, 2014

For anyone with an acute pulmonary embolism (PE), your prompt diagnosis and treatment can save a life. In patients with high-risk PE and signs of hemodynamic compromise, fibrinolysis is an established, clear choice that can reduce pulmonary artery resistance, prevent PE recurrence, and reduce mortality. Although fibrinolytic therapy is known to carry risks of major bleeding and stroke, the benefits of treatment outweigh these risks in high-risk PE. However, what is the role of fibrinolysis in normotensive patients with intermediate-risk PE? Does early reperfusion improve outcomes, as compared to standard anticoagulation with heparin? Trials seeking to answer these questions thus far have been inadequately sized, and controversy remains.

In this week’s NEJM, Meyer et al. report the findings of the largest multicenter randomized double-blinded trial of fibrinolysis for the treatment of intermediate-risk PE. Their findings help guide physicians in weighing the risks and benefits of fibrinolysis in this patient population.

In the Pulmonary Embolism Thrombolysis trial (PEITHO), 1006 patients with acute intermediate-risk PE were randomized to receive a single dose of the fibrinolytic tenecteplase plus heparin or to receive placebo plus heparin. Intermediate-risk PE was defined by the absence of hemodynamic instability and the presence of right ventricular dysfunction and myocardial injury at presentation. The primary outcome measure was a composite of death or hemodynamic decompensation within seven days of randomization. Secondary outcomes included death within seven and thirty days, as well as major extracranial bleeding and stroke within seven days.

Treatment with tenecteplase reduced the risk of death or hemodynamic decompensation (from 6% in the placebo group to 3% in the tenecteplase group, p=0.02). There was no statistically significant difference in mortality between the groups at seven or thirty days.

However, with the addition of tenecteplase, there was an increase in major bleeding (from 1% to 6%, p<0.001) and an increase in stroke (from 0.2% to 2%, p=0.003). The majority of the strokes in the tenecteplase group were hemorrhagic. Of those who suffered a hemorrhagic stroke, 40% died within a month of randomization, and the survivors were left with mild-to-moderate disability.

To further define who might benefit from fibrinolysis, the authors noted that patients 75 years of age or younger treated with tenecteplase have lower odds of death or hemodynamic decompensation and lower odds of major extracranial bleeding as compared to patients over 75. While it seems that younger patients benefit more and face fewer risks with tenecteplase than older patients, these differences in outcomes were not statistically significant.

Overall, the findings of the trial suggest that, in patients with acute intermediate-risk PE, fibrinolysis prevents hemodynamic decompensation while increasing the risk of major bleeding and stroke. Unfortunately, the trial was underpowered to detect a difference in mortality, which occurred relatively infrequently in both treatment and placebo groups. Further research and even larger study populations are needed. Nevertheless, this trial is larger than all others seeking to address the same question over the past 40 years combined, and these results can allow for more informed decisions about the treatment of intermediate-risk PE.

In the accompanying editorial, Dr. C. Gregory Elliott, Professor of Medicine at the University of Utah School of Medicine, writes, “What course should physicians chart when confronted with a normotensive patient with acute pulmonary embolism? PEITHO data provide valuable insight, but no definitive answer. PEITHO strengthens the case for risk stratification and for careful monitoring of patients with intermediate mortality risk. PEITHO also shows the relative safety of withholding fibrinolysis unless hemodynamic decompensation occurs. Therefore, it may be that overall risk can be minimized with a strategy of initial anticoagulation and rescue fibrinolysis for hemodynamic decompensation.”

For physicians and patients grappling with treatment decisions after a PE, weighing the benefits and risks of therapy is essential. As NEJM Deputy Editor Dr. John Jarcho notes, “In patients with PE, fibrinolysis is potentially beneficial but also potentially dangerous. The editors believe that clinicians will find it extremely useful to have the data from PEITHO to guide management decisions.”

Gelareh Homayounfar is a fifth-year student at Harvard Medical School who has recently completed a month-long elective at the NEJM editorial offices.

Sepsis, Albumin, and the Therapeutic Potential of Improving Oncotic Pressure

Posted by John Staples • April 9th, 2014

In physiology, as in all other sciences, no discovery is useless … we may be certain that every advance achieved in the quest of pure knowledge will sooner or later play its part in the service of man.

—    Dr Ernest Henry Starling,

The Linacre Lecture on the Law of the Heart (1915)

Modern sepsis treatment owes a conceptual debt to British physiologist Dr. Ernest Starling. Starling’s experiments suggested that increasing ventricular end-diastolic volume can increase cardiac output, and this is one of the goals in mind when septic patients are given intravenous crystalloid. In a separate line of work, Starling also described the hydrostatic and oncotic forces that ultimately cause much of this intravenous crystalloid to leak into the interstitium, resulting in pulmonary and peripheral edema that can seriously complicate a septic patient’s ICU course.

In this week’s NEJM, Dr. Pietro Caironi (Universita degli Studi di Milano, Italy) and colleagues report on the therapeutic potential of improving intravascular oncotic pressure in septic patients. The multicenter, open-label ALBIOS trial randomized 1,818 adult patients with severe sepsis to an albumin group or to a control group. Both groups received intravenous crystalloid whenever clinically indicated. The albumin group additionally received daily infusions of intravenous 20% albumin from randomization until ICU discharge or day 28 (whichever came first).

Did daily albumin infusions improve outcomes? Unfortunately not. The 28-day mortality was about 32% in both groups (p = 0.94). There was also no difference on secondary outcomes such as mortality at 90 days, severity of organ dysfunction, or ICU length of stay.

Sepsis carries a high mortality,” says cardiologist and NEJM Executive Editor Dr. Gregory D Curfman, “Rigorously conducted trials allow clinicians to confidently determine which interventions are effective in a particular patient group and which offer little to no benefit.”

Although albumin infusions didn’t confer any survival advantage to ALBIOS study subjects, some hope remains that they might be beneficial in a more select group of patients. Participants in the albumin group had higher mean arterial pressures and lower net fluid balances during the first 7 days, and a post-hoc analysis suggested daily albumin infusions might improve 90-day mortality in the subset of patients with shock. Will albumin play a part in the service of the septic patient? Perhaps the next trial will tell.

Unfolding the Diagnosis

Posted by Sara Fazio • April 4th, 2014

In our latest Clinical Problem-Solving article, a previously healthy, 25-year-old man was admitted to the hospital because of abdominal pain, nausea, vomiting, and weight loss. Fever, chills, and weakness developed 2 weeks before his admission.

In protein loss localizable to the gastrointestinal tract, in most cases, the syndrome of protein-losing enteropathy is associated with diseases localized to the small intestine. However, less commonly, the stomach may be a source of protein loss.

Clinical Pearls

What is the differential diagnosis of large gastric mucosal folds on upper endoscopy?

Large gastric mucosal folds are recognized in a variety of conditions and may reflect mucosal hyperplasia (i.e., an excessive number of mucosal epithelial cells confined to the rugae in the gastric body and fundus) or mucosal hypertrophy. As these conditions have the same gross appearance, biopsy is often necessary to determine the cause. Large nonhyperplastic gastric folds may be caused by conditions including chronic H. pylori gastritis, neoplasms such as lymphoma, adenocarcinoma, and carcinoid, as well as lymphocytic gastritis, sarcoidosis, eosinophilic gastroenteritis, and the Cronkhite-Canada syndrome. Hyperplastic gastropathies include the Zollinger-Ellison syndrome, in which there is an increased number of parietal cells, and Menetrier’s disease, in which the number of surface and foveolar mucous cells is increased.

What is the pathogenesis, epidemiology, and clinical presentation of Menetrier’s disease?

The pathogenesis of Menetrier’s disease is incompletely understood. However, the observation of elevated levels of transforming growth factor alpha (TGF-alpha) in gastric mucous cells of patients with this condition has suggested a role for TGF-alpha-induced hyperplasia. Menetrier’s disease affects men more often than women and is most common between ages 40 and 55 years. Clinical manifestations of Menetrier’s disease include epigastric pain, weight loss, nausea, vomiting, gastrointestinal bleeding, diarrhea, and protein-losing gastropathy. Hypoalbuminemia is present in 20 to 100% of patients, according to different series; this feature helps distinguish Menetrier’s disease from the Zollinger-Ellison syndrome.

Morning Report Questions

Q: How is Menetrier’s disease diagnosed and treated?

A: The diagnosis of Menetrier’s disease is usually established by demonstrating extreme foveolar hyperplasia with glandular atrophy and decreased parietal cells on biopsy in a patient with large gastric folds on endoscopy. Treatment includes medications to relieve nausea and gastric pain. A high-protein diet is prescribed to offset the loss of protein. Partial or total gastrectomy is sometimes advocated for patients with intractable pain, hypoalbuminemia, edema, hemorrhage, or pyloric obstruction, or in cases in which malignancy cannot be ruled out. A small single-blinded trial of patients with severe Menetrier’s disease treated for 1 month with cetuximab (a monoclonal antibody that blocks epidermal growth factor receptor signaling) showed significant improvement in quality of life and in biochemical indexes (increased parietal-cell mass and gastric acidity); however, more data are needed to inform the role of this medication in treatment.

Q: What infections have been associated with a Menetrier’s disease-like condition?

A: A Menetrier’s disease-like condition with transient protein-losing gastropathy, hypoalbuminemia, and marked gastric rugal hypertrophy has been reported in association with CMV [cytomegalovirus] infection, mainly in pediatric patients. Menetrier’s disease has also been reported in association with H. pylori. CMV-associated Menetrier’s disease differs from classic Menetrier’s disease in its acute self-limited course and more focal involvement of the gastric fundus, antrum, or both.

Thrombosis Risk after 6-Weeks Postpartum

Posted by Sara Fazio • April 4th, 2014

Using administrative claims data, the authors of a new study published in NEJM found significantly increased risks for primary thrombotic events beyond the 6-week postpartum period, when the risk is well recognized to be high. However, absolute increases in risk from 7 to 12 weeks after delivery were small.

Pregnancy significantly increases the risk of thrombosis. This heightened thrombotic risk rises further during the postpartum period, which is conventionally defined as the 6 weeks after delivery.

Clinical Pearls

What is known about the prothrombotic state of the postpartum period and what are current recommendations for women at high risk for venous thromboembolism?

As compared with the nonpregnant state, the 6-week postpartum period is associated with increases by a factor of 3 to 9 in the risk of  stroke, by a factor of 3 to 6 in the risk of myocardial infarction, and by a factor of 9 to 22 in the risk of venous thromboembolism. It is unknown whether these risks remain increased after the conventionally defined 6-week postpartum period. Guidelines for the treatment of thrombotic disorders during pregnancy advise the discontinuation of prophylactic therapy at 6 weeks after delivery in women at high risk for venous thromboembolism.

In this study, what was the odds ratio of having a thrombotic event within 6 weeks after delivery compared to the same period one year later?

Significantly more thrombotic events occurred within 6 weeks after delivery than during the same period 1 year later (411 events, or 24.4 events per 100,000 deliveries, vs. 38 events, or 2.3 events per 100,000 deliveries), corresponding to an absolute risk difference of 22.1 (95% confidence interval [CI], 19.6 to 24.6) per 100,000 deliveries and an odds ratio of 10.8 (95% CI, 7.8 to 15.1).

Morning Report Questions

Q: What did this study demonstrate with respect to thrombotic risk in women after the 6-week postpartum period?

A: In the period of 7 to 12 weeks after delivery, there was a modest but still significant increase in the number of thrombotic events, as compared with the same period 1 year later (95 events, or 5.6 events per 100,000 deliveries, vs. 44 events, or 2.6 events per 100,000 deliveries), corresponding to an absolute risk difference of 3.0 (95% CI, 1.6 to 4.5) per 100,000 deliveries and an odds ratio of 2.2 (95% CI, 1.5 to 3.1). The risk was no longer significantly elevated after 12 weeks, with an odds ratio of 1.4 (95% CI, 0.9 to 2.1) for the period of 13 to 18 weeks after delivery and an odds ratio of 1.0 (95% CI, 0.7 to 1.4) for the period of 19 to 24 weeks after delivery. In post hoc exploratory analyses, the thrombotic risk was increased during the period of 13 to 15 weeks after delivery (odds ratio, 2.0; 95% CI, 1.1 to 3.6) but was no longer elevated in the period of 16 to 18 weeks (odds ratio, 1.0; 95% CI, 0.6 to 1.8).

Table 2. Number and Rate of Postpartum Thrombotic Events during Sequential 6-Week Intervals after Labor and Delivery.

Q: What characteristics of patients were associated with a higher risk of postpartum thrombosis?

A: As compared with patients without postpartum thrombosis, those with postpartum thrombotic events were older, were more likely to be white or black than Hispanic or Asian, were less often privately insured, and were more likely to have risk factors for thrombosis. There was also a significantly higher risk within 6 weeks after delivery among women who had undergone cesarean section than among those who had undergone vaginal delivery.

Table 1. Baseline Characteristics of the Patients, According to the Presence or Absence of a Postpartum Thrombotic Event.