Argatroban and ultrasound-facilitated thrombolysis with alteplase in a patient with bilateral pulmonary embolism and history of heparin-induced thrombocytopenia: A case report

A 58-year-old female was admitted to the hospital with bilateral pulmonary embolism (PE) with right heart strain. Her medical history included a previous PE resulting in thrombolysis and inferior vena cava filter placement, heparin-induced thrombocytopenia, morbid obesity, and chronic pain that was treated with an epidural injection 2 weeks prior to admission. This case is unusual due to the need for alternative anticoagulation management during thrombolysis in a patient with a heparin allergy who was at increased risk for bleeding. She was initiated on argatroban to achieve therapeutic aPTTs before receiving both mechanical thrombectomy and alteplase through ultrasound-facilitated catheter-directed thrombolysis. The argatroban was reduced to a flat rate of 0.5 mcg/kg/ min during thrombolysis and was subsequently increased to achieve therapeutic aPTTs upon completion of thrombolysis. The patient was transitioned from argatroban to apixaban for lifelong anticoagulation.

Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism (FondaPPP)

We analyzed data for women who received fondaparinux for ≥7 days during pregnancy. The study retrospectively included women who received fondaparinux pre-, peri- and/or postpartum for ≥7 days for prophylaxis/venous thromboembolism (VTE) treatment at German specialist centers (2004-2010). Data on pregnancy, VTE risk factors, anticoagulant treatment, pregnancy outcome and adverse events were extracted from medical records. 120 women (mean age 31.5 years) were included. Among 84 women with prior pregnancies, 41.0% had ≥1 abortion. Anticoagulation was indicated for prophylaxis in 92.5% cases, including 82.5% women with an elevated VTE risk (82.8% thrombophilia, 34.2% VTE history). All women received low-molecular-weight heparin (LMWH) as first-line therapy; 3 also unfractionated heparin. Treatment changed to fondaparinux, due to heparin allergy (41.7%) or heparin-induced thrombocytopenia (10.0%). Fondaparinux was generally well tolerated. Adverse events included bleeding events (n = 5), abortion (n = 2), premature births (n = 2), stillbirth (n = 1), arrested labors (n = 2), injection site erythema (n = 4) and unspecified drug hypersensitivity (n = 6). No VTE events or increased liver enzymes occurred during treatment. In this retrospective study, fondaparinux was effective and well tolerated. Trial registration: ClinicalTrials.gov NCT01004939.

Impact of a multidisciplinary workflow on safety and management of patients with heparin-induced thrombocytopenia

Purpose Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin administration. Management strategies are complex and include discontinuing heparin products, initiating alternative anticoagulants, interpreting laboratory test results, documenting heparin allergies, and providing patient education. Medication error reports and a retrospective review conducted at an academic medical center revealed an opportunity for a quality improvement initiative and led to the creation of a multidisciplinary workflow for the management of HIT. In a pre-post study, the impact of the multidisciplinary workflow on the safety and management of HIT was evaluated. Methods The preimplementation group consisted of adult patients tested for suspected HIT from April 4, 2014, through May 31, 2016; the postimplementation group consisted of adult patients tested from November 1, 2016, through October 31, 2018. The primary outcome was the incidence of heparin product administration while HIT testing was ongoing. The secondary outcome was the rate of appropriate heparin allergy documentation. Results The incidence of heparin product administration while HIT testing results were pending was significantly reduced, from 54.2% to 20.0% (P < 0.001), after workflow implementation. The rate of appropriate heparin allergy documentation significantly increased, from 95.0% to 100% (P < 0.001). Conclusion Implementation of a multidisciplinary workflow for the management of HIT significantly reduced the incidence of heparin administration while testing was ongoing and improved the rate of appropriate heparin allergy documentation.

Inappropriate Listing of Heparin As an Allergy in the Electronic Medical Record Due to Misdiagnosis of Heparin-Induced Thrombocytopenia: Frequency and Consequences

Introduction Heparin-induced thrombocytopenia (HIT) is a prothrombotic complication of heparin therapy. Treatment involves discontinuation of heparin and initiation of an alternative anticoagulant. Misdiagnosis is common and may result in unnecessary exposure of thrombocytopenic patients to costly direct thrombin inhibitors and their approximate 1% daily risk of major hemorrhage. Another potential and previously unstudied consequence of misdiagnosis is the inappropriate listing of heparin as an allergy in the electronic medical record (EMR). We hypothesized that inappropriate listing of heparin as an allergy due to misdiagnosis of HIT is relatively common, often persists beyond the index hospitalization, and is associated with unnecessary avoidance of heparin as well as increased bleeding and costs. Methods We conducted a retrospective cohort study of patients with an inappropriate heparin allergy listed in the EMR due to misdiagnosis of HIT. We searched the EMR of a tertiary care center and a community hospital in our health system for patients with a new heparin allergy documented between 2004 and 2011. Patients were eligible for the study if the reason for allergy listing was suspicion for acute HIT and laboratory testing for HIT had been performed within 60 days of the allergy listing. We excluded patients that were listed as having a heparin allergy due to a remote history of suspected HIT, an adverse reaction to heparin other than HIT, or if the allergy was listed for an unknown reason. Charts of eligible subjects were reviewed and demographic, clinical, and laboratory data were extracted using a standardized data collection form. Subjects were defined as "negative for HIT" if they had a 4T score ≤3 or negative laboratory testing for HIT (ELISA <1.0 optical density units and negative serotonin release assay). All other subjects were considered to have "possible HIT." Results Among 903 patients with a new allergy to heparin documented during the time period of interest, 239 were eligible for inclusion in the study. Of these 239 subjects, 100 (42%) met the prespecified definition of "negative for HIT" (15 had a 4T score ≤3, 49 had negative laboratory testing, and 36 had both a 4T score ≤3 and negative laboratory testing) . Sixty-eight of the subjects who were negative for HIT (68%) received an alternative parenteral anticoagulant during the index admission: 52 received argatroban, 18 lepirudin, 2 both argatroban and lepirudin. No patients were treated with fondaparinux or bivalirudin. Median length of time on an alternative parenteral anticoagulant was 10.5 days. Among the 68 patients who received unnecessary argatroban and/or lepirudin, 45 (66%) met ISTH criteria for major bleeding. The majority of these subjects met criteria for a major bleed based on a decrease in hemoglobin of at least 2.0 g/dL (n=40, 58.8%) and/or transfusion of at least 2 units of packed red blood cells (n=33, 48.5%). There were 2 subjects who had a symptomatic bleed in a critical area or organ. No subjects had a fatal hemorrhage. Seventy-five (75%) of the 100 subjects that were negative for HIT had an inappropriate allergy to heparin listed in the EMR at the time of discharge from the index hospitalization, and 68 (68%) had an inappropriate allergy to heparin that remained in effect as of August 2015. These 68 patients have had 68 subsequent hospitalizations within our health system after the index admission. Conclusions We found that a substantial percentage (42%) of patients with a heparin allergy documented in the EMR due to suspected HIT were clearly negative for HIT based on review of clinical and laboratory data. Many of these patients were unnecessarily treated with a direct thrombin inhibitor (68%) and experienced major bleeding (66%). Inappropriate heparin allergy listing persisted in the EMR in most patients (75%) beyond the index hospitalization, suggesting that heparin may be unnecessarily avoided and alternative parenteral anticoagulants used in subsequent admissions. Disclosures Cuker: Bracco: Consultancy; CSL Behring: Consultancy; Genzyme: Consultancy; T2 Biosystems: Research Funding.