Drotrecogin alpha: a rational approach to the treatment of submassive pulmonary embolism?

Combining therapeutic doses of low-molecular-weight heparins and increasing doses of recombinant activated protein C - Drotrecogin alpha (activated), or DAA - is of theoretical interest with regard to the control of coagulation activation. The study by Dempfle and colleagues presents new data showing that endogenous activated protein C levels do not increase in nonseptic patients with pulmonary embolism. However, the results of the addition of these two treatments are puzzling, leaving unresolved the questionable clinical relevance of this combination and the possible increase in bleeding risk

Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention

Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study).

International audienceINTRODUCTION: In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on 7-day mortality. METHODS: Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and 7-day mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of 8 hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on 7-day mortality in all patients and in those with intracranial hemorrhage (ICH). RESULTS: Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and "other" (23%). In the whole cohort, 7-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in 7-day mortality in patients with GC-PCC-K (odds ratio (OR) = 2.15 (1.20 to 3.88); P = 0.011); this mortality reduction was also observed when only ICH was considered (OR = 3.23 (1.53 to 6.79); P = 0.002). CONCLUSIONS: Guideline-concordant VKA reversal with PCC and vitamin K within 8 hours after admission was associated with a significant decrease in 7-day mortality

ISTH guidelines for antithrombotic treatment in COVID-19

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations

Delphi-Consensus Weights for Ischemic and Bleeding Events to Be Included in a Composite Outcome for RCTs in Thrombosis Prevention

To weight ischemic and bleeding events according to their severity to be used in a composite outcome in RCTs in the field of thrombosis prevention.Using a Delphi consensus method, a panel of anaesthesiology and cardiology experts rated the severity of thrombotic and bleeding clinical events. The ratings were expressed on a 10-point scale. The median and quartiles of the ratings of each item were returned to the experts. Then, the panel members evaluated the events a second time with knowledge of the group responses from the first round. Cronbach's a was used as a measure of homogeneity for the ratings. The final rating for each event corresponded to the median rating obtained at the last Delphi round.Of 70 experts invited, 32 (46%) accepted to participate. Consensus was reached at the second round as indicated by Cronbach's a value (0.99 (95% CI 0.98-1.00)) so the Delphi was stopped. Severity ranged from under-popliteal venous thrombosis (median = 3, Q1 = 2; Q3 = 3) to ischemic stroke or intracerebral hemorrhage with severe disability at 7 days and massive pulmonary embolism (median = 9, Q1 = 9; Q3 = 9). Ratings did not differ according to the medical specialty of experts.These ratings could be used to weight ischemic and bleeding events of various severity comprising a composite outcome in the field of thrombosis prevention

Perioperative venous thromboembolism in the elderly : prevention and treatment

Pulmonary embolism remains the most common preventable cause of death in hospital. M.T. Morrel and M.S. Dunnil (Br J Surg. 1968) Introduction A number of conditions encountered frequently in the elderly, such as atrial fibrillation (AF), coronary stent placement, mechanical heart valve or cancer, predispose the older patient to thromboembolic events and require long-term prophylactic treatment; when surgery is necessary, this treatment should be adequately adjusted. Surgery itself is accompanied by an intrinsic thromboembolic risk, strictly related to direct vascular damage, inflammation, activation of coagulation factors, blood stasis and tissue trauma. Global risk is influenced by the patient’s basal conditions (older patients being at increased risk), type of surgery and perioperative management. In these patients, the risk of thromboembolic complications (TC) can be significantly reduced by adopting adequate preventive measures. This chapter investigates the optimal perioperative management of antithrombotic drugs, preventive measures toward TC and their treatment in the elderly surgical patient. Pending the publication of the European Society of Anaesthesiology Guideline on prevention of thromboembolism in anesthesia and intensive care, the American College of Chest Physicians’ Guideline on perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis is taken as the reference guidance (ACCP 2012). However, this guideline refers to the adult population, and no specific guidelines for the elderly surgical patient are currently available. Thromboembolism: Definition, Pathogenesis and Risk Factors Deep Venous Thrombosis Deep vein thrombosis (DVT) frequently occurs in the veins of the lower limbs, but is also possible in upper limb, mesenteric, pelvic and cerebral veins. Pain, swelling, tenderness, redness or skin discoloration, and warmness may manifest in the affected area; however, these signs are not always present. After one DVT episode, patients remain at increased risk of further episodes, mostly linked to surgery. Venous thromboembolism (VTE) is frequent in the elderly. It is the third most common cardiovascular condition after acute coronary infarction and stroke, affecting both hospitalized and non-hospitalized patients. It has frequent recurrence, is often overlooked and may have lethal consequences. The impact of VTE is increasing with the growing aging population; risk rises from 1/10 000 at birth to 1/100 in individuals older than 80 years (Silverstein et al. 1998)