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Correspondence
Factor XIII in the Treatment of Hemophilia A
To the Editor: Patients with hemophilia A (a deficiency of factor VIII [FVIII]) have spontaneous bleeding because of abnormal thrombin generation, which results in the formation of weak, unstable clots. The formation of these weak clots is also the result of delayed and reduced activation of…
- January 19, 2012
- N Engl J Med 2012; 366:281 - 283
- Free Full Text
One facet of the clotting abnormality in factor VIII deficiency is clot instability. Factor XIII stabilizes clots. The authors show that augmenting factor XIII levels can stabilize clot formation even when factor VIII levels are low.
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Correspondence
Acutely Injured Patients on Dabigatran
To the Editor: Trauma remains the fourth leading cause of death in the United States, with 40,000 deaths annually in persons over the age of 65. U.S. trauma centers are seeing an increasing number of severely injured elderly patients, and hemorrhagic complications and head injuries account for a…
- November 24, 2011
- N Engl J Med 2011; 365:2039 - 2040
- Free Full Text
The new oral direct thrombin inhibitor, dabigatran, is proving to be problematic in acutely injured patients, since it may promote bleeding and its effect cannot be easily reversed.
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Original Article
Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors
After exposure to factor VIII, alloantibodies (inhibitors) that neutralize factor VIII clotting function develop in approximately 30% of patients with severe hemophilia A. The development of high-titer factor VIII inhibitors (>5 Bethesda units [BU]) complicates treatment because bleeding no longer…
- November 3, 2011
- Leissinger C., Gringeri A., Antmen B., et al.
- N Engl J Med 2011; 365:1684 - 1692
- CME
In patients with hemophilia A in whom inhibitors of factor VIII develop, the prophylactic use of a factor VIII bypassing agent (anti-inhibitor coagulant complex) three times a week significantly reduced the risk of bleeding.
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Correspondence
Hemophilia A Induced by Ipilimumab
To the Editor: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4, has been reported to improve overall survival in patients with metastatic melanoma. Major side effects include immune-related adverse events. We report a rare and severe case of ipilimumab…
- November 3, 2011
- N Engl J Med 2011; 365:1747 - 1748
- Free Full Text
A case is reported in which ipilimumab therapy for melanoma was followed by the development of an autoantibody to factor VIII.
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Review Article
Mechanisms of Disease: The Coagulopathy of Chronic Liver Disease
Chronic liver disease, particularly in the end stage, is characterized by clinical bleeding and decreased levels of most procoagulant factors, with the notable exceptions of factor VIII and von Willebrand factor, which are elevated. Decreased levels of the procoagulants are, however, accompanied by…
- July 14, 2011
- Tripodi A. and Mannucci P.M.
- N Engl J Med 2011; 365:147 - 156
Conventional wisdom is that chronic liver disease is an acquired bleeding disorder. However, the imbalance between procoagulant and anticoagulant activities can also lead to thrombosis. Studies are needed to assess the value of anticoagulants.
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Perspective
Anticoagulant Options — Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran
On October 19, 2010, the Food and Drug Administration (FDA) approved dabigatran for the reduction of the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Approval was based on a multicenter, active-control trial, the Randomized Evaluation of Long-Term…
- May 12, 2011
- Beasley B.N., Unger E.F., Temple R.
- N Engl J Med 2011; 364:1788 - 1790
- Free Full Text
Last fall, the FDA approved dabigatran, in a 150-mg dose only, for reducing risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A 110-mg regimen was also effective, but the agency believes that patients should receive the higher dose.
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Review Article
Mechanisms of Disease: The Hemostatic System as a Modulator of Atherosclerosis
Cardiovascular disease is one of the leading causes of death and complications worldwide. The classic concept of atherosclerosis assigns a pivotal role to inflammation in the onset and progression of this disease. Various inflammatory cell types (e.g. macrophages, neutrophils, and lymphocytes) play…
- May 5, 2011
- Borissoff J.I., Spronk H.M.H., ten Cate H.
- N Engl J Med 2011; 364:1746 - 1760
Experimental data suggest that the hemostatic system can accelerate plaque vulnerability to thrombosis in vivo. However, clinical support for these findings remains weak. This comprehensive summary reviews the evidence.
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Images in Clinical Medicine
Ovarian-Vein Thrombosis
Figure 1.
- April 21, 2011
- Wiggermann P. and Stroszczynski C.
- N Engl J Med 2011; 364:1544
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Four days after uncomplicated delivery of a full-term infant, a 36-year-old woman presented to the ER with severe pain in the right flank. Her medical history included a remote deep-vein thrombosis of the leg and heterozygosity for the factor V Leiden mutation.
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Images in Clinical Medicine
Digital Gangrene
Figure 1.
- April 21, 2011
- Poisson J. and McCudden C.
- N Engl J Med 2011; 364:e34
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A 71-year-old man presented with palpable purpura and received a diagnosis of type II cryoglobulinemia. He had an elevated cryocrit (13%), evidence of a monoclonal IgM kappa immunoglobulin (0.8 g per deciliter), and a positive result for rheumatoid ...
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Original Article
Dalteparin versus Unfractionated Heparin in Critically Ill Patients
Venous thromboembolism is an important complication of critical illness. Patients in the intensive care unit (ICU) are at risk for venous thromboembolism because of their complex acute and chronic illnesses, as well as the need for life-support measures, sedation, analgesia and paralysis, central…
- April 7, 2011
- The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group
- N Engl J Med 2011; 364:1305 - 1314
- Free Full Text
- CME
In this trial, patients admitted to ICUs were assigned to receive dalteparin, a low-molecular-weight heparin, or unfractionated heparin for thromboprophylaxis. There was no significant between-group difference in the primary end point of incident proximal deep-vein thrombosis.
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Clinical Practice
Deep-Vein Thrombosis of the Upper Extremities
Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. Stage. A 58-year-old…
- March 3, 2011
- Kucher N.
- N Engl J Med 2011; 364:861 - 869
- CME
- Full Text Audio
This article reviews usual strategies for treating thrombosis of the upper extremities, including anticoagulation therapy and thrombolysis. The use of catheters and surgical interventions in refractory cases is also discussed.
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Editorial
Therapeutic Potential of Oral Factor Xa Inhibitors
Venous thromboembolism is the third leading cause of cardiovascular death, after myocardial infarction and stroke. Total hip or knee arthroplasty is the procedure with the highest risk of venous thromboembolism. In this issue of the Journal, two studies affirm and extend the efficacy and safety of…
- December 23, 2010
- Hylek E.M.
- N Engl J Med 2010; 363:2559 - 2561
Venous thromboembolism is the third leading cause of cardiovascular death, after myocardial infarction and stroke.¹ Total hip or knee arthroplasty is the procedure with the highest risk of venous thromboembolism.² In this issue of the Journal, two studies ...
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Original Article
Oral Rivaroxaban for Symptomatic Venous Thromboembolism
Acute venous thromboembolism (i.e. deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. Short-term treatment is effective, with the risk of recurrent disease — the major…
- December 23, 2010
- The EINSTEIN Investigators
- N Engl J Med 2010; 363:2499 - 2510
- Free Full Text
In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem.
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Original Article
Effects of CYP2C19 Genotype on Outcomes of Clopidogrel Treatment
Clopidogrel, when added to aspirin, reduces the rate of major vascular events among patients with acute coronary syndromes and atrial fibrillation. Recent reports suggest that certain common genetic variants, involving the hepatic cytochrome P-450 system, that are involved in the conversion of…
- October 28, 2010
- Paré G., Mehta S.R., Yusuf S., et al.
- N Engl J Med 2010; 363:1704 - 1714
- Free Full Text
- CME
Clopidogrel must be metabolized to an active form to be effective. Cytochrome P-450 variants resulting in slow metabolism may reduce clinical efficacy. This study in patients with acute coronary syndromes or atrial fibrillation did not confirm diminished efficacy in those with slow metabolism.
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Original Article
Fondaparinux for the Treatment of Superficial-Vein Thrombosis in the Legs
Superficial-vein thrombosis of the legs is a common condition,, with an estimated incidence that may exceed that of deep-vein thrombosis. Patients with isolated superficial-vein thrombosis — that is, without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation —…
- September 23, 2010
- Decousus H., Prandoni P., Mismetti P., et al.
- N Engl J Med 2010; 363:1222 - 1232
- Free Full Text
- CME
Superficial thrombophlebitis in the leg is associated with an increased risk of subsequent thromboembolic events; however, intervention to alter the risk has not been well studied. This study compared fondaparinux with placebo for patients with superficial thrombophlebitis in the leg.
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Editorial
Superficial Phlebitis and Phase 3.5 Trials
In this issue of the Journal, Decousus et al. report on the efficacy and safety of fondaparinux for the treatment of superficial-vein thrombosis in the legs. The results of their carefully conducted, placebo-controlled trial show that treatment with fondaparinux, at a dose of 2.5 mg once daily for…
- September 23, 2010
- Goldman L. and Ginsberg J.
- N Engl J Med 2010; 363:1278 - 1280
In this issue of the Journal, Decousus et al.¹ report on the efficacy and safety of fondaparinux for the treatment of superficial-vein thrombosis in the legs. The results of their carefully conducted, placebo-controlled trial show that treatment with ...
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Images in Clinical Medicine
Paget–Schroetter Syndrome
Figure 1.
- July 15, 2010
- Seeger M. and Bewig B.
- N Engl J Med 2010; 363:e4
- Free Full Text
- Video
A 47-year-old woman presented with swelling, pain, and reddish discoloration of the right arm and hand after strenuous effort. Ultrasonography with a microconvex probe revealed a subtotal occlusion in the subclavian vein close to the clavicle, caused by a ...
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Correspondence
Prophylactic Eculizumab after Renal Transplantation in Atypical Hemolytic–Uremic Syndrome
To the Editor: Atypical hemolytic–uremic syndrome is a rare microangiopathic hemolytic condition characterized by thrombocytopenia and acute renal failure. The prognosis for patients with atypical hemolytic–uremic syndrome with a factor H mutation is poor; 60% have end-stage renal disease or…
- May 6, 2010
- N Engl J Med 2010; 362:1746 - 1748
- Free Full Text
To the Editor: Atypical hemolytic–uremic syndrome is a rare microangiopathic hemolytic condition characterized by thrombocytopenia and acute renal failure.¹ The prognosis for patients with atypical hemolytic–uremic syndrome with a factor H mutation is ...
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Case Records of the Massachusetts General Hospital
Case 31-2009 — A 26-Year-Old Man with Abdominal Distention and Shock
Presentation of Case. Dr. Jeffrey S. Ustin (Trauma, Emergency Surgery, and Surgical Critical Care): A 26-year-old man was admitted to this hospital because of abdominal distention and shock. The patient had been well until the evening before admission, when mild abdominal pain developed, shortly…
- October 8, 2009
- Alam H.B., Fricchione G.L., Guimaraes A.S.R., Zukerberg L.R.
- N Engl J Med 2009; 361:1487 - 1496
A 26-year-old man was admitted to this hospital because of abdominal distention and shock. He had been well until the previous evening, when mild abdominal pain developed; the next day, the pain became severe, and he was unresponsive. In the emergency department, he was hypotensive, with a rigid, distended abdomen. Imaging revealed marked distention of the colon, without focal obstruction. He had a history of schizophrenia and was taking several medications.
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Correspondence
Inhibitors of Factor VIII in Hemophilia
To the Editor: Viel et al. (April 16 issue) propose that treatment of hemophilia A with factor VIII that is matched for polymorphic variants may reduce the risk of the development of factor VIII inhibitors. Their study included patients with different types of causative mutations and disease…
- July 16, 2009
- N Engl J Med 2009; 361:308 - 310
- Free Full Text
To the Editor: Viel et al. (April 16 issue)¹ propose that treatment of hemophilia A with factor VIII that is matched for polymorphic variants may reduce the risk of the development of factor VIII inhibitors. Their study included patients with different ...
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