[Complex management of type 2 heparin-induced thrombocytopenia in patients with major bleeding tendency: two case report]. / Prise en charge de la thrombopénie induite par l'héparine immuno-allergique de type 2 au travers de deux cas cliniques chez des patients à risque hémorragique majeur.

Type 2 heparin-induced thrombocytopenia (HIT 2) is a rare pro-thrombotic disorder occurring in patients treated with heparin. It is defined as a clinical-biological syndrome associating the sudden onset of a thrombocytopenia, characterized by a drop of more than 50% of the initial platelet count, and thrombosis. We report two cases of HIT 2 occurring in patients with major bleeding tendency. The first HIT occurred in a patient whose management, in accordance with current guidelines, made it possible to control the thrombocytopenia and the anticoagulation despite the complexity of adapting and monitoring treatments in the context of recent cerebral hemorrhage. The second refers to an autoimmune HIT, which occurred in a patient whose management required the use of alternative therapies to the standard treatments suggested for HIT 2, to correct the severe refractory thrombocytopenia.

Argatroban plus aspirin versus aspirin in acute ischemic stroke.

OBJECTIVES: Anticoagulant therapy in the acute phase of AIS remains controversial. The aim of this study was to investigate whether argatroban benefited early stroke outcomes compared with antiplatelet treatment. METHODS: We reviewed data from 1,485 patients with AIS hospitalized at Tianjin Union Medical Center (TUMC) between 1 January 2013 and 31 December 2015 from the TUMC registry database. Patients were divided into two groups: an antiplatelet group (aspirin 300 mg daily) and an argatroban group (argatroban 60 mg for 2 days followed by 20 mg daily; or 20 mg daily - both regimens combination with aspirin 100 mg daily). Two primary outcomes, change in NIHSS score (baseline-discharge) and intracerebral hemorrhage, were investigated. RESULTS: No major symptomatic intracerebral hemorrhages were observed in either group. Both groups had significantly decreased NIHSS scores at discharge (Z = -14.617, P < 0.001 and Z = -6.385, P < 0.001, respectively), and there were no significant group differences in NIHSS score change (Z = -1.888, P = 0.059). In the mild stroke subgroup, the argatroban group had a worse NIHSS score at discharge (Z = -6.148, P = 0.002), while the aspirin group had an improved NIHSS score (Z = -4,423, P < 0.001). In the moderate stroke subgroup, both groups had significantly decreased NIHSS scores at discharge (Z = -13.260, P < 0.001 and Z = -7.108, P < 0.001, respectively) and there were no significant group differences in NIHSS score changes (Z = -1.888, P = 0.059). CONCLUSION: Argatroban is effective and safe for the treatment of moderate AIS with similar efficacy to high-dose aspirin in the acute phase of AIS, although no additional benefit on short-term outcome was observed. For patients with mild AIS, argatroban may be inferior to high-dose aspirin.

Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke).

BACKGROUND AND PURPOSE: We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen activator (r-tPA)-treated ischemic stroke patients. METHODS: Patients treated with standard-dose r-tPA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100 µg/kg bolus) followed by infusion of either 1 (low dose) or 3 µg/kg per minute (high dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage. Probability of clinical benefit (modified Rankin Scale score 0-1 at 90 days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk, 1.0 and 95% prior intervals, 0.33-3.0). RESULTS: Ninety patients were randomized: 29 to r-tPA alone, 30 to r-tPA+low-dose argatroban, and 31 to r-tPA+high-dose argatroban. Rates of symptomatic intracerebral hemorrhage were similar among control, low-dose, and high-dose arms: 3/29 (10%), 4/30 (13%), and 2/31 (7%), respectively. At 90 days, 6 (21%) r-tPA alone, 9 (30%) low-dose, and 10 (32%) high-dose patients were with modified Rankin Scale score 0 to 1. The relative risks (95% credible interval) for modified Rankin Scale score 0 to 1 with low, high, and either low or high dose argatroban were 1.17 (0.57-2.37), 1.27 (0.63-2.53), and 1.34 (0.68-2.76), respectively. The probability that adjunctive argatroban was superior to r-tPA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. CONCLUSIONS: In patients treated with r-tPA, adjunctive argatroban was not associated with increased risk of symptomatic intracerebral hemorrhage and provides evidence that a definitive effectiveness trial is indicated. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01464788.

Use of an argatroban-based purge solution in a percutaneous ventricular assist device.

PURPOSE: The use of an argatroban-based percutaneous ventricular assist device (pVAD) purge solution in a patient with suspected heparin-induced thrombocytopenia (HIT) is described. SUMMARY: A 70-year-old woman in cardiogenic shock was admitted to a coronary care unit after being discovered unresponsive at home. A transthoracic echocardiogram revealed a low ejection fraction and findings consistent with takotsubo cardiomyopathy. Administration of multiple inotropes and vasopressors was initially required for hemodynamic support. The patient was implanted with an Impella pVAD (Abiomed, Inc., Danvers, MA) using a heparin-based purge solution; an i.v. heparin infusion was initiated for supplemental systemic anticoagulation. Over the next 24 hours, the patient's platelet count decreased from 168,000 to 37,000 cells/µL. Given a differential diagnosis that included HIT, the patient was transitioned to an argatroban-based purge solution. Due to prolonged activated partial thromboplastin times, a systemic argatroban infusion was not initiated, and the patient remained fully anticoagulated throughout pVAD support with only the argatroban-based purge solution. An HIT antibody test was negative. On hospitalization day 9 (day 6 of pVAD support with argatroban use), the patient became hemodynamically stable and was weaned off pVAD support. Three days later, the platelet count had recovered to 117,000 cells/µL (from a nadir of 21,000 cells/µL). During pVAD support, the patient developed hemolytic anemia with minimal bleeding complications. CONCLUSION: Argatroban was used as a purge solution anticoagulant in a patient with an Impella pVAD and found to be a safe and effective alternative to heparin.