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Pros and cons of new oral anticoagulants.
Authors: Bauer KA Abstract The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating effic...
Source: Hematology ASH Education Program - November 11, 2014 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Transfusion strategies in hematologic and nonhematologic disease.
Authors: Carson JL, Strair R Abstract Substantial progress has been made in our understanding of the risks and benefits of RBC transfusion through the performance of large clinical trials. More than 7000 patients have been enrolled in trials randomly allocating patients to higher transfusion thresholds (∼9-10 g/dL), referred to as liberal transfusion, or lower transfusion thresholds (∼7-8 g/dL), referred to as restrictive transfusion. The results of most of the trials suggest that a restrictive transfusion strategy is safe and, in some cases, superior to a liberal transfusion strategy. However, in patients with...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Reversing targeted oral anticoagulants.
Authors: Hoffman M, Monroe DM Abstract Dabigatran, rivaroxaban, and apixaban are orally active anticoagulants that are approved in many countries. Dabigatran inhibits thrombin, whereas rivaroxaban and apixaban are factor Xa inhibitors. In clinical trials, these novel oral anticoagulants were at least as effective as warfarin for preventing stroke in patients with atrial fibrillation, but with a lower rate of serious bleeding. However, the lack of true antidotes for these agents has caused concern when patients suffer life-threatening bleeding or trauma or require emergent invasive procedures. True antidotes are und...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Smoothing the crescent curve: sickle cell disease.
Authors: Talano JA, Cairo MS Abstract Sickle cell disease (SCD) is an inherited disorder secondary to a point mutation at the sixth position of the beta chain of human hemoglobin that results in the replacement of valine for glutamic acid. This recessive genetic abnormality precipitates the polymerization of the deoxygenated form of hemoglobin S that induces a major distortion of red blood cells (sickle red blood cells), which decreases sickle red blood cell deformability, leading to chronic hemolysis and vasoocclusion. These processes can result in severe complications, including chronic pain, end organ dysfunctio...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Does hydroxyurea prevent pulmonary complications of sickle cell disease?
Authors: Buckner TW, Ataga KI Abstract A 27-year-old man with sickle cell disease (HbSS) presents to the sickle cell clinic for follow-up after a screening echocardiogram revealed an increased tricuspid regurgitant velocity of 2.7 m/s. He has a history of 2 painful crises per year and has been hospitalized 3 times over the past 10 years for management of painful crises. He had one episode of acute chest syndrome at age 15 that was treated with an RBC exchange transfusion, supplemental oxygen, and intravenous antibiotics; he did not require mechanical ventilation. He has not had additional episodes of acute chest sy...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Pharmacogenomics of antiplatelet drugs.
Authors: Sabatine MS, Mega JL Abstract Clopidogrel, a platelet P2Y12 inhibitor, is one of the most widely prescribed drugs in cardiovascular medicine because it reduces ischemic and thrombotic complications. It is a prodrug requiring biotransformation into the active metabolite by the hepatic cytochrome 450 system, especially the CYP2C19 enzyme. Candidate gene studies and genome-wide association studies have identified loss-of-function CYP2C19 variants to be associated with a diminished pharmacologic response. Specifically, compared with noncarriers, carriers of at least one copy of a loss-of-function CYP2C19 allel...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Monitoring target-specific oral anticoagulants.
Authors: Konkle BA Abstract Target-specific oral anticoagulants are approved for use for the prevention of stroke in atrial fibrillation and for the prevention and treatment of venous thrombosis without the need for laboratory monitoring. However, there are clinical settings in which laboratory measurement of anticoagulant effect is needed. These may include patients with life-threatening bleeding or those requiring emergency surgery, in the setting of renal or hepatic failure, or patients with thrombosis on therapy. This chapter reviews the use of laboratory testing to assess the anticoagulant effect of these drug...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Future prospects for contact factors as therapeutic targets.
Authors: Gailani D Abstract Anticoagulants currently used in clinical practice to treat or prevent thromboembolic disease are effective, but place patients at increased risk for serious bleeding because they interfere with plasma enzymes (thrombin and factor Xa) that are essential for hemostasis. In the past 10 years, work with genetically altered mice and studies in baboons and rabbits have demonstrated that the plasma contact proteases factor XI, factor XII, and prekallikrein contribute to the formation of occlusive thrombi despite having limited roles in hemostasis. In the case of factor XI, epidemiologic data f...
Source: Hematology ASH Education Program - February 20, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Mechanical circulatory support: balancing bleeding and clotting in high-risk patients.
Authors: Baumann Kreuziger L, Massicotte MP Abstract Mechanical circulatory support (MCS) provides a bridge to heart transplant in children and adults with life-threatening heart failure and sustains patients ineligible for transplant. Extracorporeal membrane oxygenation (ECMO) provides temporary support for patients in cardiac or pulmonary failure through external gas exchange and continuous flow of blood. Because the median time to heart transplant exceeds event-free time on ECMO, pulsatile left ventricular assist devices (LVADs) are used to support infants and children. Continuous flow LVADs are preferred in ado...
Source: Hematology ASH Education Program - December 10, 2015 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Sickle cell disease: when and how to transfuse.
Authors: Howard J Abstract Blood transfusion remains an important therapeutic intervention in patients with sickle cell disease (SCD), aiming to both increase the oxygen carrying capacity of blood and to reduce the complications of vaso-occlusion. Simple, manual exchange and automated exchange can be effective in reducing the acute and chronic complications of SCD, and the advantages and disadvantages of each methodology mean they all have a role in different situations. Evidence for the role of emergency transfusion in the management of the acute complications of SCD, including acute pain and acute chest syndrome,...
Source: Hematology ASH Education Program - December 4, 2016 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Anticoagulation with VADs and ECMO: walking the tightrope.
Authors: Raffini L Abstract The evolution of devices for mechanical circulatory support (MCS), including ventricular assist devices (VADs) for patients with heart failure and extracorporeal membrane oxygenation (ECMO) for patients with acute cardiac or respiratory failure, has improved survival for subsets of critically ill children and adults. The devices are intricate and complex, allowing blood to bypass the heart or lungs (or both). As blood flows through these artificial devices, normal hemostasis is disrupted, coagulation is promoted, and in the absence of anticoagulation, a thrombus may form in the device, r...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Chronic organ failure in adult sickle cell disease.
Authors: Vichinsky E Abstract Sickle cell disease is now a chronic adult illness characterized by progressive multiorgan failure, particularly involving the brain and kidney. The etiology is multifactorial; it includes hemolysis and nitric oxide deficiency. As patients age, most experience neurologic insult. Twenty-five percent of older adults have had a clinical stroke and at least half of the population have had a silent infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with neuroimaging and neurocognitive testing is recommended. Identification and correction of modifiable risk factors ...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

What is the role of screening for pulmonary hypertension in adults and children with sickle cell disease?
Authors: Willen SM, Gladwin MT Abstract Patient case: An 18-year-old male patient with homozygous hemoglobin SS disease was evaluated for progressive dyspnea and elevated tricuspid regurgitant jet velocity (TRV) on echocardiography. The patient's case is described in detail in Lancet1 He had been treated with regular transfusions since childhood for stroke, had rare episodes of vaso-occlusive pain episodes, and did not take narcotic pain medications. He presented with progressive severe dyspnea on exertion and lower extremity edema. His laboratory tests were notable for a total hemoglobin level of 11.8 g/dL and hem...
Source: Hematology ASH Education Program - December 10, 2017 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Adult and pediatric mechanical circulation: a guide for the hematologist.
Authors: Kreuziger LB, Massicotte MP Abstract Mechanical circulatory support (MCS) is the overarching term that encompasses the temporary and durable devices used in patients with severe heart failure. MCS disturbs the hematologic and coagulation system, leading to platelet activation, activation of the contact pathway of coagulation, and acquired von Willebrand syndrome. Ischemic stroke and major hemorrhage occur in up to 30% of patients. Hematologists are an essential part of the MCS team because they understand the delicate balance between bleeding and clotting and alteration of hemostasis with antithrombotic th...
Source: Hematology ASH Education Program - December 7, 2018 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Sickle cell disease: a comprehensive program of care from birth.
Authors: de Montalembert M, Tshilolo L, Allali S Abstract As more children are appropriately being diagnosed, the burden of sickle cell disease is increasing greatly in Africa and in high-resource countries such as the United States and Europe. Early management is mandatory, but newborn screening is not implemented everywhere. Point-of-care testing devices are increasingly being used in low-resource countries, showing good sensitivity and specificity. Because the diagnosis is often traumatic for the families, the announcement should be made by an experienced person. The development of care networks is urgently requ...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

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