Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban.

BACKGROUND AND PURPOSE: Rivaroxaban has recently been approved for stroke prevention in atrial fibrillation. However, lack of an effective antidote represents a major concern in the event of intracerebral hemorrhage (ICH). The aims of the present study were to establish a murine model of ICH associated with rivaroxaban, and to examine the effectiveness of different hemostatic factors in preventing excess hematoma expansion. METHODS: In C57BL/6 mice receiving 10 or 30 mg/kg rivaroxaban by gastric gavage, plasma concentration, prothrombin time, and coagulation factor activities were measured repeatedly. Thirty minutes after inducing ICH by intrastriatal collagenase-injection, mice received an intravenous injection of either saline, prothrombin complex concentrate (100 U/kg), murine fresh frozen plasma (200 µL), or recombinant human Factor VIIa (1 mg/kg). ICH volume was quantified on brain cryosections and using hemoglobin spectrophotometry 24 hours later. RESULTS: Rivaroxaban in 30 mg/kg dose substantially increased the hematoma volume in ICH induced by 0.060 U collagenase. Prothrombin complex concentrate, fresh frozen plasma, or Factor VIIa prevented excess hematoma expansion caused by anticoagulation. Prevention of hematoma expansion by prothrombin complex concentrate was dose-dependent. None of the 3 agents completely corrected the prolonged prothrombin time, although they restored the activities of deficient FII and X. CONCLUSIONS: Prothrombin complex concentrate, Factor VIIa, and fresh frozen plasma prevent excess intracerebral hematoma expansion in a murine ICH model associated with rivaroxaban. The efficacy and safety of this reversal strategy must be further evaluated in clinical studies.

[The "Seville" Consensus Document on Alternatives to Allogenic Blood Transfusion. Sociedades españolas de Anestesiología (SEDAR), Medicina Intensiva (SEMICYUC), Hematología y Hemoterapia (AEHH), Transfusión sanguínea (SETS) Trombosis y Hemostasia (SETH)]. / Documento «Sevilla¼ de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica.

The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, "C", "D", or "E", thus indicating the need for further controlled studies.

[Recombinant activated factor VII as a life-saving therapy for severe postpartum haemorrhage unresponsive to conservative traditional management]. / Intérêt du facteur VII activé recombinant dans l'hémorragie de la délivrance sévère réfractaire à la prise en charge conservatrice conventionnelle.

Postpartum haemorrhage remains the main cause of maternal morbidity and mortality. Treatment aims at maintaining hemodynamic circulation and preventing shock by stopping blood loss both medically and surgically. We report two cases of major postpartum haemorrhage due to uterine atony. Patients developed haemorrhagic shock and severe coagulation disorders (nadir values of PTT were <10% and fibrinogen was <0.1 g/l). Well-codified medical (ocytocin, sulprostone) and surgical management (ligation of both hypogastic arteries in the two cases completed by staged uterine ligation in one case) failed to stop bleeding. Recently, several case reports described successful use of recombinant activated factor VII (rFVIIa) in scheduled surgery, trauma and major postpartum haemorrhage. Thus, after transfusion of more than one blood mass and failure of surgical haemostasis to stop bleeding, rFVIIa (60 microg/kg) was given. A single iv bolus injection stopped ongoing diffuse haemorrhage in the two cases. No further transfusion was required afterwards in both patients. RFVIIa might thus be a strong complementary agent in the management of major postpartum haemorrhage. Optimal dose, timing and safety characteristics of rVIIa administration remain to be determined. One patient developed four weeks later thrombosis of both ovarian veins, a complication that can be related to either rFVIIa or to the staged uterine ligations performed during surgery.

Activated recombinant human coagulation factor VII therapy for intracranial hemorrhage in patients with hemophilia A or B with inhibitors. Results of the novoseven emergency-use program.

Activated recombinant human coagulation factor VII (rFVIIa) is a promising new therapeutic agent for patients with hemophilia A or B with inhibitors who experience serious bleeding episodes or who need coverage during surgical procedures. This open-label, uncontrolled, emergency-use study evaluated the efficacy and safety of rFVIIa in 11 hemophiliac patients and 1 FVII-deficient patient with life-threatening intracranial hemorrhage previously unresponsive to one or more alternative therapies. rFVIIa effectively controlled intracranial hemorrhage in 10 of the 12 patients. Patients with hemophilia A or B received an average of 96.9 rFVIIa injections over 14.7 days with a mean total administration of 153.3 mg, corresponding to 8.1 mg/kg. Most reported adverse events were considered to be unrelated to rFVIIa therapy. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of central nervous system bleeding in patients with hemophilia A or B with inhibitors.