In April 2007 a 48-year-old woman with a history of hepatitis C and anti-phospholipid antibody syndrome presented with a hemoglobin (Hb) of 5.3g/dL. Lactate dehydrogenase and bilirubin were elevated at 582U/L and 66µmol/L respectively. Severe autoimmune hemolytic anemia due to cold agglutinins was diagnosed based on a positive DAT (C3B and C3D positive, IgG negative) and detection of cold agglutinins. The patient was discharged 4 days later with a Hb of 8.3g/dL after plasma exchange and transfusion of 3 units of RBCs. Immunosuppressive therapy was initially avoided due to the risk of hepatitis C activation. Treatment over the next 12 months consisted of as needed RBC transfusions and IVIg infusions. Treatment with corticosteroids occurred only during 1 of 2 hospital admissions for severe anemia – the patient otherwise refused corticosteroid treatment. Although responses to IVIg were consistently favorable they were short lived. Rituximab was administered in an effort to achieve a more sustained treatment response. The dose of 375mg/m2weekly for 4 weeks was administered in August 2008. A dramatic but transient decrease in IVIg requirements was observed. Periodic treatment with IVIg was continued over the next 19 months until a second rituximab course was administered in June 2010. IVIg has been required on only 6 occasions in the almost three years since the second rituximab course (see Figure 1). To determine the efficacy of rituximab in this condition, we searched the MEDLINE and EMBASE databases. Articles citing the use of rituximab to treat mixed-type or cold autoimmune hemolytic anemia (CAIHA) were identified. Ten studies (summarized in Table 1) and 43 case reports/series (48 total cases) met our criteria for inclusion. A complete response (CR) required Hb>12g/dL and the sustained absence of hemolysis. Disappearance of cold agglutinins was not required for a CR. A partial response (PR) required an improvement of symptoms, transfusion independency, and either: Hb>10g/dL or at least 2.0g/dL above pre-treatment levels, or a decrease in serum IgM concentration by at least 50%. Non-responders met neither CR nor PR criteria. Ages of the 26 male and 22 female patients ranged from 1-85 years with a median of 62 years. Diagnoses of CAIHA were reported in 40 cases, and mixed-type in 8. On average, patients had received 3 modes of treatment prior to rituximab. CRs were observed in 34 patients (70.8%), PRs in 7 (14.6%), and NRs in 7 (14.6%). Three of the 7 non-responders experienced an improvement in condition despite not meeting response criteria. Adverse effects were reported in only 3 cases and included a post-infusion low-grade fever, transient lymphopenia, and agranulocytosis (possibly due to CMV reactivation and not rituximab therapy).Table 1Studies employing rituximab to treat cold or mixed autoimmune hemolytic anemia.CitationStudy typeNumber of participants, Age rangeAIHA typeOutcome (CR, PR, NR)Barcellini et al, 2012prospective multicenter9, 30-71cold16.6%, 33.3%, 0Berentsen et al, 2010prospective multicenter29, 39-87cold21%, 55%, 24%Berentsen et al, 2001prospective6, 54-80cold14%, 57%, 29%Berentsen et al, 2004prospective27, 51-91cold3%, 51%, 46%Berentsen et al, 2006retrospective multicenter52, 51-96*coldsingle agent: 5%, 53%, 42%in combination: 25%, 42%, 33%Cholankeril et al, 2012retrospective single institution6, 62-894 cold, 2 mixedOR 100%, median Hb rise of 1.8g/dLPeñalver et al, 2010retrospective multicenter9, 20-86*coldCR and MR 66.7%Schöllkopf et al, 2006prospective multicenter20, 54-86cold5%, 40%, 55%Dierickx et al, 2009retrospective multicenter14, 1-87*cold28.6%, 35.7%, 35.7%Zecca et al, 2003prospective1, 1.3coldresponderZaja et al, 2003not specified1, 72coldcomplete responder*age range reflects entire study population, not CAIHA subgroupOR=overall response, MR=maintained response In summary, we report a case of CAIHA. A literature summary supported the efficacy of rituximab for this condition. Based on our observations we recommend the use of rituximab over alternative therapies for patients with CAIHA to reduce symptoms, need for transfusion and reduce exposure to immunosuppressive drugs (Grade 2C Recommendation). Disclosures: Off Label Use: Rituximab was used to treat cold autoimmune hemolytic anemia. Crowther:Asahi Kasai: Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; CSL Behring: Speakers Bureau; Leo Pharma: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Consultancy; Octapharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity’s Board of Directors or advisory committees.
1115 Rapid reversal of vitamin K antagonists (VKAs) is required when patients experience acute bleeding or are in need of urgent surgery. Traditionally, in Canada, the only therapeutic option for warfarin reversal was fresh frozen plasma (FFP); recently a four factor prothrombin complex concentrate (PCC) has become available. In this retrospective chart review, we examined the use of Octaplex®, a four factor (FII, FVII, FIX, FX), solvent/detergent (S/D) treated and nanofiltered PCC, in a tertiary care centre over 18 months (November 2008 to May 2010), to determine its efficiency and safety in VKA reversal. The PCC was used 85 times in 82 patients. All patients had received warfarin prior to PCC administration. Patients received a mean dose of 1792 (1000 – 3500) IU of PCC for treatment of bleeding (36), urgent surgery (40) and excessively elevated international normalized ratio (INR) (8). One patient received PCC for an unknown indication and is excluded from the results presented here; a further 6 patients did not have INR tests done immediately before and immediately after PCC administration and are excluded from the laboratory results presented here. The mean INR before administration of the PCC was 5.10 (range 1.2 – 25). The mean INR after administration of the PCC was 1.43 (range 0.9 – 3.3). Forty-seven of seventy-nine [59.5%, 95% CI 47.9 to 70.4%] administrations resulted in an INR of 1.3 or less and 60/79 [75.9%, 65.0 to 84.9%] resulted in an INR of 1.5 or less. Of the 40 patient encounters where PCC was administered due to need for urgent surgery, 39 were able to undergo the procedure. Three patients experienced a thromboembolic event; one had a venous thromboembolism due to a clot extension of a previously diagnosed left leg DVT 8 days after PCC administration, another had a non-occlusive renal vein clot 8 days after PCC administration and the last had a cilioretinal artery occlusion 238 days after receiving PCC. No other adverse events potentially related to PCC were observed. We conclude that the prothrombin complex concentrate Octaplex® provides efficacious, safe and rapid reversal of VKA therapy. Disclosures: Crowther: Pfizer: Consultancy, Research Funding; Sanofi Aventis: Consultancy, Research Funding; Leo Laboratories: Consultancy, Research Funding; Artisan: Consultancy. Off Label Use: The product described in this abstract is not available in the US. The described use is “on label” in Canada.
3123 Poster Board III-60 Introduction Despite recent evidence, controversy remains regarding the optimal method of recurrent thrombosis prevention in patients with antiphospholipid antibodies (APLA) and prior thrombosis. Specifically, although two randomized trials have supported the efficacy of “usual intensity warfarin” (administered to a target INR of 2.0 to 3.0) there remains a dearth of prospective data examining this treatment. The aim of our study was to confirm that patients with prior thrombosis and an APLA had a low risk of recurrent thrombosis while being treated with warfarin administered to achieve an INR of 2.0 to 3.0. Methods We examined the annual rate of recurrent thrombosis in patients with prior thrombosis and APLA who had all been treated with OAT (oral anticoagulant therapy) to achieve a target INR of 2.0 to 3.0. Eligible patients had to have had at least one prior objectively confirmed arterial or venous thrombosis and at least one positive standardized test for an APLA. Patients were selected from the Victoria Hospital, and follow up appointments were conducted through the hospital's thrombosis clinic. Consenting patients underwent a baseline clinical examination with the intent to be followed every six months for evidence of recurrent thrombosis, adverse consequences of anticoagulation therapy, or until death. Results Eighty three patients (mean age 50.5 years; 50 females) were enrolled; one patient was lost to follow up and did not contribute data to the analyses. Median follow up was 12 months (Range 5-18 months). No patients experienced a recurrent thrombotic event. 10 patients (12.2%) had a minor bleeding event (5 had significant ecchymosis, two had rectal bleeding, two had vaginal bleeding, and one had hematuria). No major bleeding events occurred. One patient had a presumed transient ischemic attack (TIA). One patient (1.2%) died during follow up due to multi-system organ failure in the context of a failing hepatic allograft. Conclusion Patients with previous thrombosis and an APLA have a low risk of recurrent thrombosis while having a target INR of 2.0 to 3.0. “Usual intensity warfarin” therapy appears to be an adequate method of thromboprophylaxis in these patients. Disclosures Crowther: BI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Artisan Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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