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Unfractionated heparin versus low molecular weight heparin for avoiding heparin‐induced thrombocytopenia in postoperative patients

Heparin is a natural agent used to prevent clot formation in the vessels. Two types of heparins are widely used, unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Heparin‐induced thrombocytopenia (HIT) is an adverse reaction that can occur during treatment with heparin. It is common in practice and its most important consequence is a paradoxical increase in the risk of clotting (thromboembolic) complications. A number of factors are thought to influence its frequency, including the type of heparin and the type of patient, with patients who have had a surgery at higher risk. We compared the risk of HIT in people who had had surgery and had been exposed to UFH or LMWH. A better understanding of this problem will allow safer management of postoperative patients who need thromboprophylaxis with heparin.

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

Version: 2017

Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis

The 4Ts is a pretest clinical scoring system for heparin-induced thrombocytopenia (HIT). Although widely used in clinical practice, its predictive value for HIT in diverse settings and patient populations is unknown. We performed a systematic review and meta-analysis to estimate the predictive value of the 4Ts in patients with suspected HIT. We searched PubMed, Cochrane Database, and ISI Web of Science for studies that included patients with suspected HIT, who were evaluated by both the 4Ts and a reference standard against which the 4Ts could be compared. Quality of eligible studies was assessed by QUADAS-2 criteria. Thirteen studies, collectively involving 3068 patients, fulfilled eligibility criteria. A total of 1712 (55.8%) patients were classified by 4Ts score as having a low probability of HIT. The negative predictive value of a low probability 4Ts score was 0.998 (95% CI, 0.970-1.000) and remained high irrespective of the party responsible for scoring, the prevalence of HIT, or the composition of the study population. The positive predictive value of an intermediate and high probability 4Ts score was 0.14 (0.09-0.22) and 0.64 (0.40-0.82), respectively. A low probability 4Ts score appears to be a robust means of excluding HIT. Patients with intermediate and high probability scores require further evaluation.

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

Version: 2012

Systematic review on heparin-induced thrombocytopenia in children: a call to action

BACKGROUND: Heparin-induced thrombocytopenia (HIT) has increasingly been reported in children as an indication for use of new alternative anticoagulant drugs (NAADs).

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

Version: 2013

Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially devastating complication of anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Our objective was to determine and compare the incidences of HIT in surgical and medical patients receiving thromboprophylaxis with either UFH or LMWH. All relevant studies identified in the MEDLINE database (1984-2004), not limited by language, and from reference lists of key articles were evaluated. Randomized and nonrandomized controlled trials comparing prophylaxis with UFH and LMWH and measuring HIT or thrombocytopenia as outcomes were included. Two reviewers independently extracted data on thromboprophylaxis (type, dose, frequency, and duration), definition of thrombocytopenia, HIT assay, and rates of the following outcomes: HIT, thrombocytopenia, and thromboembolic events. HIT was defined as a decrease in platelets to less than 50% or to less than 100 x 10(9)/L and positive laboratory HIT assay. Fifteen studies (7287 patients) were eligible: 2 randomized controlled trials (RCTs) measuring HIT (1014 patients), 3 prospective studies (1464 patients) with nonrandomized comparison groups in which HIT was appropriately measured in both groups, and 10 RCTs (4809 patients) measuring thrombocytopenia but not HIT. Three analyses were performed using a random effects model and favored the use of LMWH: (1) RCTs measuring HIT showed an odds ratio (OR) of 0.10 (95% confidence interval [CI], 0.01-0.2; P = .03); (2) prospective studies measuring HIT showed an OR of 0.10 (95% CI, 0.03-0.33; P < .001); (3) all 15 studies measured thrombocytopenia. The OR was 0.47 (95% CI, 0.22-1.02; P = .06). The inverse variance-weighted average that determined the absolute risk for HIT with LMWH was 0.2%, and with UFH the risk was 2.6%. Most studies were of patients after orthopedic surgery.

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

Version: 2005

How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia?

This review assessed the frequency of heparin-induced thrombocytopenia (HIT) associated with venous thromboembolism in patients given unfractionated or low molecular weight heparin for thromboprophylaxis or treatment. The authors concluded that unfractionated but not low molecular weight heparin is associated with high-frequency HIT. Poor reporting, inadequate literature searches, failure to address study quality and inappropriate synthesis mean that the authors' conclusions are unlikely to be reliable.

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

Version: 2006

Treatment of heparin-induced thrombocytopenia: a critical review

This review assessed the effects of replacing heparin with new anticoagulants in patients with heparin-induced thrombocytopenia. The authors' conclusions appear to be that lepirudin and argatroban are effective anticoagulants, but the evidence was limited and further research is required. The authors correctly acknowledged the limitations of evidence from the included observational studies.

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

Version: 2004

No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin: a metaanalysis

This was a generally well-conducted meta-analysis exploring the risk of thrombocytopenia in patients prescribed low-molecular-weight heparin or unfractionated heparin for venous thromboembolism. The authors performed a thorough quality assessment of the included studies and used appropriate statistical methods to combine the data. The conclusions seem reliable based on the evidence presented.

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

Version: 2007

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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Meta regression analysis to indirectly compare dalteparin to enoxaparin for the prevention of venous thromboembolic events following total hip replacement

BACKGROUND: Patients undergoing elective total hip replacement (THR) surgery are at an increased risk for venous thromboembolic events (VTEs). Dalteparin and enoxaparin are recommended as thromboprophylaxis for at least 10 days in these patients. Even though both agents have proven clinical effectiveness through placebo controlled studies, there have been no head to head trials to assess comparative effectiveness. Indirect statistical techniques were used to compare safety and efficacy between dalteparin and enoxaparin following THR surgery.

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

Version: 2011

Low molecular weight heparin-induced skin necrosis: a systematic review

This review examined published reports of low molecular weight heparin-induced skin necrosis. The authors concluded that most patients have heparin-induced thrombocytopenia syndrome and most patients have a good outcome. The review methods were not reported and the conclusions did not adequately reflect the limited evidence from a small number of patients.

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

Version: 2005

Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care [Internet]

This report evaluates the level of evidence currently available to support the effectiveness and safety of using recombinant activated coagulation factor VII (rFVIIa) for clinical indications not approved by the U. S. Food and Drug Administration (FDA). rFVIIa is approved for a variety of uses in hemophilia patients who have developed antibody inhibitors that compromise the use of standard factor replacement. Use of this costly biologic product has expanded beyond these hemophilia-related indications to encompass a range of off-label uses, most of which are in-hospital uses. These uses differ substantially from the drug’s FDA approved label. The purpose of this report is two-fold: (1) To document the full range of clinical indications for which rFVIIa is being used and the types of studies available to evaluate these uses and (2) To provide a comparative effectiveness review of rFVIIa vs. usual care for several in-hospital clinical indications: intracranial hemorrhage, massive bleeding secondary to trauma, and the selected surgical procedures of cardiac surgery, liver transplantation, and prostatectomy.

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

Version: May 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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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
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Low-molecular-weight heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review

The authors concluded that low molecular weight heparin could not be recommended routinely and that further trials were required to test patient-specific endpoints. The authors' conclusions were appropriate for the evidence presented.

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

Version: 2009

Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation [Internet]

Approximately 250,000 Canadians are affected by atrial fibrillation (AF). Stroke is a complication of AF, and Canadians with AF are five times more likely to have a stroke and are twice as likely to die than individuals without AF. AF and stroke are more common among the elderly.

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

Version: April 9, 2012
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Prevention of thrombosis in children with cancer and tunnelled CVCs

Children with cancer are at higher risk of thrombosis than children without cancer. This is a result of the disease itself but also of the cancer treatment and the presence of a central venous catheter. In this review, we investigated whether systemic treatments can prevent thrombosis. We identified six studies; two studies investigated low molecular weight heparins, one antithrombin supplementation and one cryoprecipitate and/or fresh frozen plasma supplementation; one study compared antithrombin supplementation with low molecular weight heparin and antithrombin supplementation, and another investigated warfarin. The addition of low molecular weight heparins to antithrombin supplementation did result in a lower number of symptomatic thromboses. This was statistically significant. We could not detect an effect of systemic preventive treatments in comparison with no treatment, and no difference was noted in the number of participants who suffered from major or minor bleeding. However, the overall number of participants was very small; a similar study with a larger population of participants might yield different results.

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

Version: 2013

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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Heparin versus normal saline for maintaining an open (patent) arterial line

For most patients who require intensive care, the success of clinical decision making and interventions is dependent on the accuracy of blood pressure and pulse measurements of samples taken using an arterial catheter. Maintaining the patency of these catheters is therefore essential for minimizing both patient discomfort (blood clots and reduced blood flow to a limb, infection and scarring) and additional expenses incurred by the need to replace a blocked catheter. This summary of a Cochrane review presents what we know from the available research about which solution (heparin or normal saline) is more effective in maintaining the patency of arterial catheters in adult patients. Heparin is a powerful drug in terms of its ability to prevent clots from forming in the catheter, but its use is not without risk of bleeding, an allergic reaction and low platelet counts. Patients can experience serious adverse events when given heparin.

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

Version: 2014

Heparin for treatment of the neonate with thrombosis (blood clot formation)

Background: Among pediatric patients, newborns are at highest risk of thrombosis owing to differences in the neonatal hemostatic system (the system that helps bleeding to stop). Abnormal blood clot formation might start in an artery (blood going away from the heart) or in a vein (blood going toward the heart). Different management strategies have been described, ranging from "wait and see" to active management aimed at dissolving clots (fibrinolytic) and preventing clot formation (anticoagulant). Possible side effects of active management include secondary bleeding. However, in some cases, thrombosis can be a life‐threatening event requiring active management. Despite limited evidence on anticoagulant treatment in neonates, heparin has become a standard therapy. Current recommendations and dosing regimens for anticoagulative treatment are based on uncontrolled studies and have been adapted from data derived from reports on adult and pediatric patients. The evidence is current to May 2016.

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

Version: 2016

Low molecular weight heparin for prevention of venous thromboembolism in adults with lower‐leg immobilization in an outpatient setting

Immobilization of the lower limb with plaster cast or brace in adult patients is associated with deep venous thrombosis (DVT). In order to prevent this complication preventive treatment with anticoagulants is often used, most commonly low molecular weight heparin (LMWH). Different indications for the use of LMWH are given in existing national guidelines. Therefore we searched the literature for trials on this topic, in order to develop an evidence‐based stand on this matter.

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

Version: 2014

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