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Antithrombin III for critically ill patients

Antithrombin is a small particle produced by the liver. It deactivates several substances which affect the ability of the blood to form clots. Its activity is increased many‐fold by the drug heparin, which enhances the binding of antithrombin to clotting factors so that the blood does not form clots. Antithrombin also reduces inflammation in the human body. Inflammation is the body's attempt at self protection to remove harmful stimuli and begin healing processes. Inflammation is thus not always a bad process.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2016

Aptrotinin and tranexamic acid may show promise in decreasing blood loss and blood transfusion requirements

Blood loss during liver resection (partial removal of liver) is one of the important factors affecting the post‐operative complications of patients. Allogeneic blood transfusion (using blood donated by a different individual) is associated with increased morbidity and lower survival in patients with liver cancer. This systematic review was aimed at determining whether any medical treatment decreased blood loss and decreased allogeneic blood transfusion requirements in patients undergoing liver resections. This systematic review included six trials with 849 patients. All trials had high risk of bias ('systematic error') as well of play of chance ('random error'). The trials included comparison of medicines (such as aprotinin, desmopressin, recombinant factor VIIa, antithrombin III, and tranexamic acid) with controls (no medicines). There was no difference in the death or complications due to surgery or long‐term survival in any of the comparisons. Fewer patients required transfusion of blood donated by others when aprotinin or tranexamic acid were compared to controls not receiving the interventions. The other comparisons did not decrease the transfusion requirements. However, there is a high risk of type I errors (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included and the small sample size in each trial as well as the inherent risk of bias (systematic errors). Aprotinin and tranexamic acid show promise in the reduction of blood transfusion requirements in liver resections. Further randomised clinical trials with low risk of bias (systematic errors) and low risk of play of chance (random errors) which assess clinically important outcomes (such as death and complications due to operation) are necessary to assess any pharmacological interventions aimed at decreasing blood transfusion and blood transfusion requirements in liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

Prevention of occlusion of small veins in the liver after blood‐forming stem cell transplantation

We reviewed evidence about the effects of medications to prevent blockage of small veins in the liver (veno‐occlusive disease or VOD) in people who undergo blood‐forming stem cell transplantation (HSCT).

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Novel oral anticoagulants (DOACs) for the treatment of pulmonary embolism

Venous thromboembolism is a condition where a blood clot forms in the deep veins (DVT) (most commonly of the leg) and can travel up to block the arteries in the lungs (pulmonary embolism). Pulmonary embolism is life‐threatening and occurs in approximately 3 to 4 per 10,000 people. The chances of getting a pulmonary embolism can increase with risk factors, including previous clots, prolonged periods of immobility (such as travelling on aeroplanes or bed rest), cancer, exposure to oestrogens (pregnancy, oral contraceptives or hormone replacement therapy), blood disorders (thrombophilia) and trauma. A pulmonary embolism is diagnosed by determining the risk factors and scanning the lungs to check for a clot. If a pulmonary embolism is confirmed, patients are treated with an anticoagulant. This prevents further clots from forming. Until recently, the drugs of choice were heparin, fondaparinux and vitamin K antagonists. However, these drugs can cause side effects and have limitations. Recently two classes of direct oral anticoagulants (DOACs) have been developed: direct thrombin inhibitors (DTI) and factor Xa inhibitors. There are particular reasons why oral DTIs and factor Xa inhibitors might be better medicines to use. They can be given orally, they have a predictable effect, they do not require frequent monitoring or re‐dosing and they have few known drug interactions. This review measures the effectiveness and safety of these new drugs compared with conventional treatment.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2017

Antithrombin for respiratory distress syndrome in preterm infants

Antithrombin (AT) is a substance that is produced by the liver and that plays an important role in the control of blood clotting and the subsequent breakdown of the clot. Critically ill infants, such as those born prematurely with immature lungs leading to respiratory distress (Respiratory Distress Syndrome; RDS) have low concentrations of AT in the blood. Studies have been conducted to examine whether preterm infants with RDS benefit from the administration of AT. In our systematic review, we found that preterm infants with RDS do not benefit from therapy with AT and may be harmed.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

Factor Xa inhibitors for acute coronary syndromes

The use of unfractionated heparin and low molecular weight heparins greatly reduces the risk of mortality and morbidity in acute coronary syndromes. However, their use has been associated with a risk of adverse events such as major bleeding, which has prompted researchers to seek safer alternative anticoagulants such as the synthetic inhibitors of the Xa factor ‐ a crucial enzyme in the coagulation cascade. We systematically reviewed efficacy and safety of factor Xa inhibitors in treating acute coronary syndromes when compared to unfractionated heparins or low molecular weight heparins. A total of four trials involving 27,976 subjects was included. Xa inhibitors reduced all‐cause mortality at 30 days, with the effect becoming more significant at 180 days. However, no significant differences were observed in the incidence of myocardial infarction or reinfarction at 30 days. Factor Xa inhibitors were found to be safer than enoxaparin, a low molecular weight heparin, due to reduced incidences of major and minor bleeding at 30 patients in patients receiving conservative treatment.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Novel oral anticoagulants for the treatment of deep vein thrombosis

Deep vein thrombosis (DVT) is a condition in which a blood clot forms in the deep vein of the leg or pelvis. It affects approximately 1 in 1000 people. If it is not treated, the clot can travel in the blood and block the arteries in the lungs. This life‐threatening condition is called a pulmonary embolism (PE) and occurs in approximately 3 to 4 per 10,000 people. The chances of getting a DVT can be increased if people have certain risk factors. These include previous clots, prolonged periods of immobility (such as travelling on aeroplanes or bed rest), cancer, exposure to oestrogens (pregnancy, oral contraceptives or hormone replacement therapy), trauma and blood disorders such as thrombophilia (abnormal blood clotting). A DVT is diagnosed through determining the risk factors and performing an ultrasound of the leg veins. If a DVT is confirmed, people are treated with an anticoagulant. This medicine prevents further clots from forming. Until recently, the drugs of choice were heparin, fondaparinux and vitamin K antagonists. However, these drugs can cause side effects and have limitations. Two further classes of novel oral anticoagulants have been developed: these are called direct thrombin inhibitors (DTI) and factor Xa inhibitors. There are particular reasons why oral DTIs and factor Xa inhibitors might now be better medicines to use. They can be given orally, they have a predictable effect, they do not require frequent monitoring or re‐dosing and they have few known drug interactions. This review measures the effectiveness and safety of these new drugs with conventional treatment.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Comparison of two types of blood thinning drugs for preventing blood clots in people with atrial fibrillation

People with atrial fibrillation, a condition that causes the heart to beat irregularly, are at an increased risk of the formation of blood clots. Such clots can block blood vessels and cause severe organ damage (infarction), for example in the brain or lungs. Various guidelines recommend that patients with atrial fibrillation should be treated with blood thinning drugs that can prevent the formation of blood clots. Serious side effects of such treatment are bleedings (for example into the brain) that can cause serious disability or even death.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Myocardial Infarction with ST-Segment Elevation: The Acute Management of Myocardial Infarction with ST-Segment Elevation [Internet]

When myocardial blood flow is acutely impaired (ischaemia), and often not provoked by exertion, a person will commonly suffer more prolonged pain; this is referred to as acute coronary syndrome (ACS). The underlying common pathophysiology of ACS involves the erosion or sudden rupture of an atherosclerotic plaque within the wall of a coronary artery. Exposure of the circulating blood to the cholesterol-rich material within the plaque stimulates blood clotting (thrombosis), which obstructs blood flow within the affected coronary artery. This coronary obstruction may be of short duration, and may not result in myocardial cell damage (necrosis), in which case the clinical syndrome is termed unstable angina. Unstable angina may result in reversible changes on the electrocardiogram (ECG) but does not cause a rise in troponin, a protein released by infarcting myocardial cells. Ischaemia which causes myocardial necrosis (infarction) will result in elevated troponin. When the ischaemia-causing infarction is either short-lived or affects only a small territory of myocardium the ECG will often show either no abnormality or subtle changes. This syndrome is termed non-ST-segment elevation myocardial infarction (NSTEMI). The diagnosis and immediate management of STEMI and the management of unstable angina and NSTEMI is addressed in other NICE Clinical Guidelines (CG95 and CG94).

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: July 2013

Venous Thromboembolism Prophylaxis in Orthopedic Surgery [Internet]

This is an evidence report prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center (EPC) examining the comparative efficacy and safety of prophylaxis for venous thromboembolism in major orthopedic surgery (total hip replacement [THR], total knee replacement [TKR], and hip fracture surgery [HFS]) and other nonmajor orthopedic surgeries (knee arthroscopy, injuries distal to the hip requiring surgery, and elective spine surgery).

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: March 2012
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Comparative Effectiveness of Warfarin and Newer Oral Anticoagulants for the Long-Term Prevention and Treatment of Arterial and Venous Thromboembolism [Internet]

The Veterans Health Administration (VHA) System serves a largely older, male population with a high prevalence of chronic atrial fibrillation (AF) and venous thromboembolism (VTE). Many veterans with chronic AF have risk profiles for stroke that, according to current clinical guidelines, place them in a risk group where chronic anticoagulation is recommended. Adjusted-dose warfarin has been the preferred approach to chronic anticoagulation in the VHA, and in many VHA settings, specialized therapeutic drug-monitoring services provide high-quality warfarin treatment. However, the advent of newer anticoagulants with the promise of simplified long-term anticoagulation requires reconsideration of current treatment practices. The purpose of this systematic review was to study the comparative effectiveness of warfarin and the newer oral anticoagulants used for the long-term prevention and treatment of arterial and venous thromboembolism. An evaluation of newer oral anticoagulants for VTE prophylaxis in the perioperative period will be the subject of a later report.

Evidence-Based Synthesis Program - Department of Veterans Affairs (US).

Version: April 2012

Anticoagulation Monitoring and Reversal Strategies for Dabigatran, Rivaroxaban, and Apixaban: A Review of Clinical Effectiveness [Internet]

The purpose of this report is to review the clinical effectiveness and cost of strategies to identify over-anticoagulation states and strategies to treat bleeding associated with the use of dabigatran, rivaroxaban, and apixaban, with the broader aim to help inform future listing recommendations and decisions, as well as clinical practice.

CADTH Therapeutic Review - Canadian Agency for Drugs and Technologies in Health.

Version: April 2012

Comparative Effectiveness of Newer Oral Anticoagulants and Standard Anticoagulant Regimens for Thromboprophylaxis in Patients Undergoing Total Hip or Knee Replacement [Internet]

Venous thromboembolic (VTE) events are important causes of morbidity in elective total hip replacement (THR) and total knee replacement (TKR) procedures. Current guidelines recommend thromboprophylaxis in patients undergoing THR or TKR, although the American Academy of Orthopaedic Surgeons (AAOS) guidelines suggest individual assessment of patients when choosing the specific thromboprophylaxis strategy. Low molecular weight heparin (LMWH) and adjusted-dose warfarin are the most commonly used anticoagulants for thromboprophylaxis in the United States, but a number of other treatment options are available, including unfractionated heparin, aspirin, mechanical devices, and newer oral anticoagulants.

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: December 2012

Oral direct factor Xa inhibitors versus low-molecular-weight heparin to prevent venous thromboembolism in patients undergoing total hip or knee replacement: a systematic review and meta-analysis

This review concluded that compared with low-molecular-weight heparin, low doses of oral factor Xa inhibitors achieved a small absolute reduction in symptomatic deep vein thrombosis without the increase in bleeding associated with high doses. Despite problems with missing data these conclusions appear likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Novel oral anticoagulants in atrial fibrillation: a meta-analysis of large, randomized, controlled trials vs warfarin

This review concluded that novel oral anticoagulants seemed to be superior to warfarin, for reducing the composite of stroke or systemic embolism, lowering all-cause mortality, and halving the number of haemorrhagic strokes, in patients with atrial fibrillation. Despite some limitations to the trials and the review, the conclusions are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Hypertension in Pregnancy: The Management of Hypertensive Disorders During Pregnancy

This clinical guideline concerns the management of hypertensive disorders in pregnancy and their complications from preconception to the postnatal period. For the purpose of this guideline, ‘pregnancy’ includes the antenatal, intrapartum and postpartum (6 weeks after birth) periods. The guideline has been developed with the aim of providing guidance in the following areas: information and advice for women who have chronic hypertension and are pregnant or planning to become pregnant; information and advice for women who are pregnant and at increased risk of developing hypertensive disorders of pregnancy; management of pregnancy with chronic hypertension; management of pregnancy in women with gestational hypertension; management of pregnancy for women with pre-eclampsia before admission to critical care level 2 setting; management of pre-eclampsia and its complications in a critical care setting; information, advice and support for women and healthcare professionals after discharge to primary care following a pregnancy complicated by hypertension; care of the fetus during pregnancy complicated by a hypertensive disorder.

NICE Clinical Guidelines - National Collaborating Centre for Women's and Children's Health (UK).

Version: August 2010
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Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing [Internet]

Venous thromboembolism (VTE) is a condition in which a blood clot (a thrombus) forms in a vein and then dislodges to travel in the blood (an embolus). A venous thrombus most commonly occurs in the deep veins of the legs or pelvis; this is then called a deep vein thrombosis (DVT). Blood flow through the affected vein can be limited by the clot, and it can cause swelling and pain in the leg. If it dislodges and travels to the lungs, to the pulmonary arteries, it is called a pulmonary embolism (PE), which in some cases may be fatal. VTE as a term includes both DVT and PE. Major risk factors for VTE include a prior history of DVT, age over 60 years, surgery, obesity, prolonged travel, acute medical illness, cancer, immobility, thrombophilia (an abnormal tendency for the blood to clot) and pregnancy.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: June 2012
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Menopause: Full Guideline

In summary, a large number of women in the UK experience menopausal symptoms which, in many cases, can significantly affect their quality of life. It is probable that a minority of these women seek medical treatment and for those who do there is considerable variation in the help available, with many being told that the symptoms will get better with time. Since symptoms may often continue for 7 years or more, this advice is inappropriate and help should be offered where possible. Women need to know about the available options and their risks and benefits, and be empowered to become part of the decision-making process.

NICE Guideline - National Collaborating Centre for Women's and Children's Health (UK).

Version: November 12, 2015

Sepsis: Recognition, Assessment and Early Management

Sepsis is a clinical syndrome caused by the body's immune and coagulation systems being switched on by an infection. Sepsis with shock is a life-threatening condition that is characterised by low blood pressure despite adequate fluid replacement, and organ dysfunction or failure. Sepsis is an important cause of death in people of all ages. Both a UK Parliamentary and Health Service Ombudsman enquiry (2013) and UK National Confidential Enquiry into Patient Outcome and Death (NCEPOD, 2015) have recently highlighted sepsis as being a leading cause of avoidable death that kills more people than breast, bowel and prostate cancer combined.

NICE Guideline - National Guideline Centre (UK).

Version: July 2016
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Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital

Venous thromboembolism (VTE) is a term used to include the formation of a blood clot (a thrombus) in a vein which may dislodge from its site of origin to travel in the blood, a phenomenon called embolism. A thrombus most commonly occurs in the deep veins of the legs; this is called deep vein thrombosis. A dislodged thrombus that travels to the lungs is known as a pulmonary embolism.

NICE Clinical Guidelines - National Clinical Guideline Centre – Acute and Chronic Conditions (UK).

Version: 2010

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