Managing Complications of Anticoagulant Therapy

2004 ◽  
Vol 17 (5) ◽  
pp. 327-346 ◽  
Author(s):  
Maureen A. Smythe ◽  
William E. Dager ◽  
Nima M. Patel
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Warfarin Therapy ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Skin Reactions ◽  
Life Threatening ◽  
Heparin Compounds

Understanding the frequency, risk factors, and management of anticoagulant-induced adverse events will assist clinicians in optimizing patient outcomes. The most frequent adverse event of all anticoagulants is major bleeding. Risk factors for major bleeding have been identified with the heparin compounds, the direct thrombin inhibitors (DTIs), fondaparinux, and warfarin therapy. Understanding these risk factors can help prevent bleeding events. For cases of clinically significant bleeding, reversal agents exist primarily for heparin and warfarin. Although less common, nonbleeding adverse events of anticoagulant therapy can also be life threatening. The heparin compounds are associated with the development of heparin-induced thrombocytopenia (HIT) and osteoporosis. HIT can result in life-threatening thrombosis and is usually managed with a DTI. Nonbleeding adverse events with warfarin therapy include skin reactions and the development of venous limb gangrene. Appropriate initiation of warfarin therapy may decrease the risk of venous limb gangrene.

scholarly journals Treatment of bleeding complications in patients on anticoagulant therapy

Blood ◽  
2019 ◽  
Vol 133 (5) ◽  
pp. 425-435 ◽  
Author(s):  
Siavash Piran ◽  
Sam Schulman
Keyword(s):  
Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Laboratory Data ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Bleeding Complications ◽  
Emergency Setting ◽  
Antifibrinolytic Agents ◽  
Different Types ◽  
Life Threatening

Abstract Anticoagulant therapy is often refrained from out of fear of hemorrhagic complications. The most frequent type of major bleeding is gastrointestinal, but intracranial hemorrhage has the worst prognosis. Management of these complications in patients on anticoagulants should follow the same routines as for nonanticoagulated patients, as described here with the previously mentioned bleeds as examples. In addition, for life-threatening or massive hemorrhages, reversal of the anticoagulant effect is also crucial. Adequate reversal requires information on which anticoagulant the patient has taken and when the last dose was ingested. Laboratory data can be of some help, but not for all anticoagulants in the emergency setting. This is reviewed here for the different types of anticoagulants: vitamin K antagonists, heparins, fondaparinux, thrombin inhibitors and factor Xa inhibitors. Specific antidotes for the latter are becoming available, but supportive care and nonspecific support for hemostasis with antifibrinolytic agents or prothrombin complex concentrates, which are widely available, should be kept in mind.

scholarly journals Case Report. Non-Obvious, Post-Traumatic, Life-Threatening Bleeding in Two Elderly Patients

2017 ◽  
Vol 3 (2) ◽  
pp. 79-83
Author(s):  
Rafael García Carretero
Keyword(s):  
Case Report ◽  
Side Effects ◽  
Elderly Patients ◽  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonist ◽  
Life Threatening ◽  
Post Traumatic ◽  
Main Complication

Abstract The main complication of anticoagulant therapy is major bleeding. Clinicians are usually aware of these side effects and are careful when managing the therapeutic range of vitamin K antagonist drugs. But major bleeding, while lifethreatening, can be overlooked if there are no visible signs of bleeding. Two cases are described in which inaccurate diagnoses lead to inadequate treatment.

Abstract TP70: Incidence of Serious Adverse Events Following Acute Stroke: Data From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Szymon Stodolak ◽  
Lisa J Woodhouse ◽  
Nikola Sprigg ◽  
Daniel Bereczki ◽  
Philip M Bath
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Acute Stroke ◽  
Oral Feeding ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Life Threatening ◽  
History Of ◽  
Randomised Controlled ◽  
Relationship Of

Background: Reporting of serious adverse events (SAEs) is an essential safety procedure in randomised controlled trials. Risk factors for SAEs post-stroke and the relationship of SAEs with outcome were studied in the ENOS trial. Methods: ENOS assessed glyceryl trinitrate (GTN, 5 mg) vs no GTN for 7 days in 4,011 patients with acute stroke and high blood pressure. Information on SAEs was collected up to day 90. SAEs were adjudicated centrally with blinding to treatment assignment. Results: SAEs were reported in 1022 (25.5%) patients, 43.8% of whom died. Patients who suffered SAEs were more likely to be older (mean age 74.2 vs. 69.0 years, p<0.001) and have a history of atrial fibrillation (AF) (relative risk [RR] 1.80, p<0.001). Patients with non-oral feeding at baseline were more vulnerable to SAEs (RR 2.14, p<0.001) and fatal SAEs (RR 3.77, p<0.001) as compared with those with oral feeding. Males were at less risk than females to suffer an SAE (RR 0.83, p<0.001), as were smokers (RR 0.73, p<0.001). Smokers also suffered fewer fatal SAEs (RR 0.55, p<0.001). GTN did not increase the incidence of SAEs. The most common type of SAE was pneumonia (6% incidence) with a high risk of death (RR 9.29, p<0.001). Conclusions: SAEs are associated with a range of risk factors that should be taken into account in clinical practice. AF and non-oral feeding status were associated with increased, and smoking with reduced, risk of of SAEs. Incidence of pneumonia was a common and life threatening issue amongst patients.

scholarly journals Spontaneous retroperitoneal hematoma in a COVID-19 patient

2021 ◽  
Vol 2 (4) ◽  
pp. 377-385
Author(s):  
Ana Sekulić ◽  
Olivera Marinković ◽  
Davor Mrda ◽  
Borislav Tošković ◽  
Marija Zdravković ◽  
...  
Keyword(s):  
Risk Factors ◽  
Case Report ◽  
Mortality Rate ◽  
Anticoagulant Therapy ◽  
Psoas Muscle ◽  
Bleeding Complications ◽  
Thromboembolic Events ◽  
Life Threatening ◽  
The Right ◽  
Radiological Examinations

Introduction: The infection caused by the SARS-CoV-2 virus is known to cause a hypercoagulable condition resulting in acute thrombotic events. Thromboembolic events occur in as many as 21.0% of cases with a mortality rate of about 74.0% in persons infected with COVID-19. Anticoagulant therapy is used in severe COVID-19 infections in order to prevent thrombosis and has been shown to reduce mortality. The use of anticoagulants is not without risks. Bleeding complications can range from mild to severe or even life-threatening, such as retroperitoneal bleeding into the psoas muscle. Case report: We present a case of a patient who developed a complication of bleeding into the retroperitoneal space during the treatment of bilateral bronchopneumonia caused by the SARS-CoV-2 virus. After the diagnosis was established, on the basis of a clinical examination, laboratory and radiological examinations, and after initial conservative treatment at the UHMC Bežanijska kosa, the patient underwent embolization of the left lumbar arteries from the right inguinal fossa, during procedural analgosedation. After the radiological procedure, the recovery was satisfactory, but due to the impossibility of resorption of an encapsulated hematoma with a zone of central necrosis, a mini left lumbotomy and evacuation of the hematoma were performed. The patient was discharged from the hospital on the 23rd day of admission in stable general condition. Conclusion: The effect of anticoagulant therapy, especially in patients with existing risk factors, early diagnosis, and prompt therapy of spontaneous retroperitoneal hematomas is imperative to reduce mortality from this severe complication, in patients with the COVID-19 infection.

Controversies of Anticoagulation Reversal in Life-Threatening Bleeds

2010 ◽  
Vol 23 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Stephen Rolfe ◽  
Stella Papadopoulos ◽  
Katherine P. Cabral
Keyword(s):  
Factor Viia ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Anticoagulant Reversal ◽  
Life Threatening ◽  
Minimize Blood Loss ◽  
Warfarin Reversal ◽  
Optimal Approach ◽  
Newer Anticoagulants

Therapeutic anticoagulation with heparins, warfarin, and anti-Xa inhibitors carry an inherent risk of complications due to their multifaceted pharmacokinetic and pharmacodynamic properties as well as narrow therapeutic ranges. When an anticoagulated patient presents with a major or life-threatening bleed, immediate and effective therapy may be necessary to reverse the effects of the anticoagulant, minimize blood loss, and reduce patient morbidity and mortality. Optimal agents and strategies for anticoagulant reversal are limited, particularly for newer anticoagulants. The literature describing such strategies available to reverse the effects of anticoagulants in the setting of a bleed is limited, and therefore many controversies exist. Thus, as new anticoagulants become available, without a specific agent for reversal, the concerns and controversies related to this topic must be addressed. The purpose of this review is to discuss the management of major or life-threatening bleeds by addressing the following controversies: (1) the use of recombinant factor VIIa for rapid reversal of warfarin in patients with intracerebral hemorrhage, (2) the role of prothrombin complex concentrate in emergent warfarin reversal, and (3) the optimal approach to reverse newer anticoagulants such as low molecular weight heparins, fondaparinux, and direct thrombin inhibitors.

scholarly journals Evaluation of Bivalirudin’s Effect on International Normalized Ratio to Determine an Appropriate Strategy for Transitioning to Warfarin

2018 ◽  
Vol 34 (3) ◽  
pp. 117-122
Author(s):  
Andrea Fetea ◽  
Brian E. Gulbis ◽  
Andrea C. Hall
Keyword(s):  
Primary Endpoint ◽  
Major Bleeding ◽  
Partial Thromboplastin Time ◽  
International Normalized Ratio ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Limited Data ◽  
Heparin Induced Thrombocytopenia ◽  
Secondary Endpoints

Background: Direct thrombin inhibitors are recommended in confirmed or suspected heparin-induced thrombocytopenia. False elevation of the international normalized ratio (INR) occurs with these agents making bridging to warfarin challenging. There is limited data regarding bivalirudin’s effect on INR. Objective: To evaluate bivalirudin’s effect on the INR and determine a strategy for transitioning to warfarin. Methods: This was a retrospective observational study. Included patients were >18 years old receiving primary bridging therapy with overlapping bivalirudin and warfarin for at least 72 hours. Patients with administration of alternate anticoagulants during the transition interval or active major bleeding within 48 hours prior to bivalirudin initiation were excluded. The primary endpoint was to determine the effect on INR at first therapeutic activated partial thromboplastin time after bivalirudin initiation and prior to warfarin initiation. Secondary endpoints included change in INR 12 and 24 hours after bivalirudin initiation, change in INR 4 hours after bivalirudin cessation, and incidence of major bleeding or new thrombotic events. Results: Thirty-four patients met study criteria. For the primary endpoint, the change in INR at first therapeutic activated partial thromboplastin time was 0.37 (range = 0.28-0.48), which occurred at 8.4 hours (range = 4.6-14.2; n = 14). INR increased at 12 and 24 hours by a median of 0.55 and 0.5 from baseline, respectively. Median change in INR 4 to 8 hours post-bivalirudin cessation was −0.48. Conclusion: Targeting an INR > 2.5 when bridging to warfarin will account for this false elevation and maintain an INR above 2.0 on bivalirudin discontinuation.

scholarly journals FEIBA™ for Reversal of Direct Oral Anticoagulant Associated Major Bleeding

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1540-1540
Author(s):  
Joseph Shaw ◽  
Gregoire Le Gal ◽  
Melanie Tokessy ◽  
Nancy Cober ◽  
Elianna Saidenberg ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Events ◽  
Vitamin K ◽  
Major Bleeding ◽  
Conservative Management ◽  
Oral Anticoagulant ◽  
Direct Oral Anticoagulant ◽  
Bleeding Events ◽  
Life Threatening ◽  
Bleeding Episodes

Abstract Introduction: Direct oral anticoagulants (DOACs) are indicated for the prevention of systemic embolism in patients with atrial fibrillation and for the prevention and treatment of venous thrombosis. Although DOACs offer advantages over the vitamin K antagonists, some hesitancy remains over their use given the lack of specific antidotes for management of life threatening bleeding events. In vivo studies, case reports and case series have shown that prothrombin complex concentrate (PCC) and activated PCC might potentially be used to control life threatening bleeding in patients with DOAC-associated bleeding episodes. Herein we describe management and outcomes of DOAC-associated life threatening bleeding events using an activated PCC (FEIBA™). Methods: A retrospective review of patients presenting with DOAC-associated (dabigatran, rivaroxaban or apixaban) life threatening bleeding to The Ottawa Hospital between January 2013 and June 2014 are included. Patients received 25 – 50 units/kg of FEIBA™. The primary outcome was adverse thrombotic and embolic events during follow-up. Secondary outcome was symptomatic control of bleeding. Results: Nine patients presented to hospital with life threatening bleeding episodes (post trauma: n=3; spontaneous bleeding: n=6). Spontaneous episodes included epistaxis or gastro-intestinal bleeding. Baseline characteristics are depicted in Table 1. A majority of patients had atrial fibrillation (n=8) and received rivaroxaban (n=5). The last dose of DOAC was taken within 24 hours of bleeding events for all patients. All patients received supportive management, interventions/procedures aimed at attaining source control of bleeding when possible, and transfusion of FEIBA™ for reversal of anticoagulant effect. Adverse events after receiving FEIBA™ were uncommon with one patient experiencing a TIA with expressive aphasia and visual field deficit on the evening of FEIBA™ transfusion; deficits resolved by the time of hospital discharge. Two patients with GI bleeding continued to have ongoing bleeding despite FEIBA™ administration and two patients died as a result of major bleeding. Conclusions: In this cohort of patients with major bleeding associated with DOACs, FEIBA™ administration, in addition to supportive care, was helpful in minimizing further complications of most bleeding events and associated with a low rate of adverse events. Prospective studies are needed to evaluate benefits and harms of FEIBA™ for management of DOAC associated major bleeding. Abstract 1540. Table 1: Patients with Life-threatening Bleeding Patient (Age and Gender) Indication for DOAC [AF(CHADS2); VTE] DOAC and Dosage Site of Bleeding Intervention/ Procedure Units of PRBCs Transfused Additional Treatment FEIBA™ Dose (IU)(1st/2nd) Adverse Events post-FEIBA™ Administration Survived Hospitalization 85 Male AF (2) Rivaroxaban 20 mg daily Epistaxis Nasal Packing 0 -- 3275 -- Yes 86 Male AF (2) Rivaroxaban 20 mg daily LGIB Angiogram, no embolization performed 10 Vitamin K 3159/ 2952 -- Yes 84 Male AF (2) Dabigatran 110 mg BID Orbital vitreous hemorrhage Surgical repair of ruptured globe 0 -- 1812 -- Yes 92 Male AF (6) Apixaban 5 mg BID Left hand Conservative management 1 Tranexamic acid 2718 TIA Yes 85 Male VTE Rivaroxaban 20 mg daily LGIB Conservative management 2 Vitamin K 1740 -- Yes 90 Female AF (5) Rivaroxaban 20 mg daily SDH Conservative management 0 -- 3275 -- No; died of major bleed 93 Female AF (6) Apixaban 2.5 mg BID LGIB Conservative management 4 -- 2241 -- No 93 Male AF (3) Rivaroxaban 15 mg daily UGIB Upper endoscopy, no intervention 4 Vitamin K 3000 -- No; died of major bleed and septic shock 81 Male AF (4) Dabigatran 110 mg BID LGIB Upper endoscopy and colonoscopy, no interventions 4 -- 3362 -- No AF = atrial fibrillation; BID = twice daily; CHADS = congestive heart failure, hypertension, age, diabetes, stroke; DOAC = direct oral anticoagulant; IU = international units; LGIB = lower gastrointestinal bleeding; PRBC = packed red blood cells; SDH = subdural hematoma; TIA = transient ischemic attack; UGIB = upper gastrointestinal bleeding; VTE = venous thromboembolism Disclosures Off Label Use: FEIBA is an activated prothrombin complex concentrate that was used during management of life threatening bleeding in patients with direct oral anticoagulant-associated bleeding episodes..

scholarly journals Heparin-induced thrombocytopenia

Medicina ◽  
2008 ◽  
Vol 44 (9) ◽  
pp. 723
Author(s):  
Dagmara Reingardienė
Keyword(s):  
Platelet Count ◽  
Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Laboratory Confirmation ◽  
Blood Clots ◽  
Life Threatening ◽  
Low Platelet Count

In clinical use for over 50 years, heparin is an important and widely used anticoagulant for the prophylaxis or treatment of thromboembolic disease as well as other numerous clinical situations. Ordinarily, heparin prevents clotting and does not affect the platelets, components of the blood that help to form blood clots. However, heparin can also cause heparin-induced thrombocytopenia. Two distinct types of heparininduced thrombocytopenia can occur: nonimmune and immune mediated. Nonimmune heparin-induced thrombocytopenia, which occurs most frequently, is characterized by a mild decrease in the platelet count and is not harmful. The second type, immune-mediated heparin-induced thrombocytopenia, occurs much less frequently but is dangerous. Immune-mediated heparin-induced thrombocytopenia causes much lower platelet count. Paradoxically, despite a very low platelet count, patients who suffer from heparin-induced thrombocytopenia are at risk for arterial or venous thrombosis. In this review article, there are discussed about pathogenesis of heparin-induced thrombocytopenia, other causes of thrombocytopenia, clinical features, laboratory confirmation of diagnosis, and management of patients (direct thrombin inhibitors, other therapies, duration of therapy, and use of oral anticoagulants). Prognosis and prophylaxis of this life-threatening disorder, which can develop from the use of unfractionated or (less commonly) low-molecular-weight heparin, are also discussed.

Abstract 15944: Fondaparinux: A Low-hanging Fruit in Heparin-induced Thrombocytopenia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
José P Sousa ◽  
rogerio teixeira ◽  
Carolina Lourenço ◽  
Lino Gonçalves
Keyword(s):  
Primary Endpoint ◽  
Retrospective Studies ◽  
Meta Analysis ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Bleeding Events ◽  
Heparin Induced Thrombocytopenia ◽  
Life Threatening ◽  
Thrombotic Complications ◽  
Related Mortality

Introduction: Heparin-induced thrombocytopenia (HIT) is a life-threatening disease associated with thromboembolic complications. Therefore, its treatment should comprise non-heparin anticoagulants. As opposed to direct thrombin inhibitors (DTI) and danaparoid, fondaparinux use is generally regarded as off-label. Purpose: To perform a meta-analysis to appraise fondaparinux efficacy and safety in the setting of HIT. Methods: We systematically searched Embase, MEDLINE, Web of Science, Cochrane CENTRAL and Google Scholar databases, using the terms “heparin-induced thrombocytopenia” and “fondaparinux”, form inception to June 1, 2020. Studies targeting thrombotic complications, bleeding events, platelet count and mortality were included. The primary endpoint was a composite of arterial and venous thromboembolism, amputation, gangrene and HIT-related mortality. Therapeutic arms were those of fondaparinux and a standard non-heparin anticoagulant. A random-effects model with Mantel-Haenszel method was performed to calculate pooled odds ratios (OR) and their 95% confidence interval (CI). Results: We encompassed 7 retrospective studies, which accounted for 630 patients, of which 302 were under fondaparinux. The remaining were treated with danaparoid, argatroban, lepirudin or bivalirudin. There were 109 primary endpoint events, 80 hemorrhages, 13 persistent or recurring thrombocytopenia cases and 98 deaths. Fondaparinux was found not only to numerically reduce thromboembolism (6 studies, OR 0.28, 95% CI 0.06-1.20, P 0.09, i 2 45%) but also to significantly lessen primary endpoint events (7 studies, OR 0.26, 95% CI 0.10-0.67, P 0.006, i 2 66%). In parallel, a tendency towards a lower rate of bleeding with fondaparinux use was also unveiled (7 studies, OR 0.78, 95% CI 0.50-1.21, P 0.27, i 2 0%). Likewise, thrombocytopenia cases were less common in the fondaparinux arm (4 studies, OR 0.16, 95% IC 0.05-0.57, P 0.004, i 2 0%). Finally, fondaparinux use was also associated with a survival benefit (6 studies, OR 0.26, 95% IC 0.08-0.90, P 0.03, i 2 54%). Conclusions: Fondaparinux seems to be at least as safe and more effective than other non-heparin anticoagulants, in the setting of HIT. Prospective studies are needed to demonstrate this hypothesis.

Anticoagulation in Hypercoagulable Conditions: Special Considerations in the Treatment and Prevention of Venous Thromboembolism

2004 ◽  
Vol 17 (5) ◽  
pp. 308-316
Author(s):  
Ann K. Wittkowsky
Keyword(s):  
Risk Factors ◽  
Thrombin Inhibitors ◽  
Moderate Intensity ◽  
Direct Thrombin Inhibitors ◽  
Adequate Treatment ◽  
Treatment And Prevention ◽  
Heparin Resistance ◽  
Increased Risk ◽  
Venous Thromboembolic Events

Patients with hypercoagulable conditions, including malignancy, are at increased risk of recurrent venous thromboembolic events (VTE). The general approach to treatment and prevention of VTE in patients with thrombophilia is similar to that of patients who present with VTE associated with transient risk factors, including immobility, trauma, and surgery. However, several important issues must be considered in the initial management of acute VTE, in the long-term prevention of VTE following an initial event, and in VTE prophylaxis in patients with hypercoagulable conditions. Patients with antithrombin deficiency are prone to heparin resistance and may require concurrent antithrombin concentrates or anticoagulation with direct thrombin inhibitors for adequate treatment of acute VTE. In patients with malignancy, low-molecular-weight heparins have been found to be more effective than unfractionated heparin for the initial treatment of VTE. Long-term prevention is preferred for most patients with hypercoagulable conditions, and the latest trials show that low-intensity warfarin is not as effective as typical moderate-intensity therapy for chronic therapy. Primary prophylaxis of asymptomatic carriers is not warranted unless they are exposed to additional risk factors, including surgery, trauma, immobilization, and pregnancy. Prolonged prophylaxis may be appropriate in patients with malignancy who undergo surgical procedures.

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