Dose sparing and the lack of a dose-response relationship with an influenza vaccine in adult and elderly patients - a randomized, double-blind clinical trial.

AIMS: The currently licensed seasonal trivalent influenza vaccines contain 15 µg haemagglutinin per strain for adult, and up to 60 µg for elderly patients. However, due to recent shortages, dose sparing to increase production capacity would be highly desirable. In the present study, we attempted to find a dose-response relationship for immunogenicity and, thus, the optimal dose for seasonal influenza vaccines in adult and elderly patients. METHODS: A total of 256 subjects, including adult (aged 18-60 years) and elderly (aged over 60 years) individuals, were enrolled. Subjects were randomly assigned in a 1:1:1:1 ratio to receive a whole-virion, aluminium-adjuvanted trivalent influenza vaccine containing 3.5, 6, 9 or 15 µg haemagglutinin of seasonal A/H1N1, A/H3N2 and B influenza antigens manufactured by Omninvest Ltd., Hungary. Serum antibody titres against the vaccine virus strains were measured by haemagglutination inhibition. RESULT: All vaccines were well tolerated. All four vaccines fulfilled all three immunogenicity licensing criteria, as determined by the European Committee for Proprietary Medicinal Products (CPMP)/Biotechnology Working Party (BWP)/214/96 guideline for all three virus strains and both age groups. The 3.5 µg vaccine showed 28% less seroconversion compared to the 15 µg dose in terms of influenza AH3N2 in the adult group (95% confidence interval -51, -3; P < 0.05). All other doses showed no significant difference in immunogenicity compared with the licensed vaccine containing 15 µg haemagglutinin. CONCLUSIONS: Our data suggested that significant dose sparing is possible with the use of whole-virion vaccines and aluminium adjuvants, without compromising safety. This could have significant economic and public health impacts.

[Safety data of the new, reduced-dose influenza vaccine FluArt after its first season on the market]. / Az új, csökkentett dózisú, hazai gyártású influenzavakcina (FluArt) forgalomba hozatalát követo elso szezonjának biztonságossági vizsgálata.

INTRODUCTION: The currently licensed seasonal influenza vaccines contain split, subunit or whole virions, typically in amounts of 15 µg hemagglutinin per virus strain for adult and up to 60 µg in elderly patients. AIM: The present study reports safety data of the newly licensed, reduced dose vaccine with 6 µg of hemagglutinin per strain produced by Fluart (Hungary) after its first season on the market. The main objective of enhanced safety surveillance was to detect a potential increase in reactogenicity and allergic events that is intrinsic to the product in near real-time in the earliest vaccinated cohorts. METHOD: The study methods were based on the Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU by the European Medicines Agency. STATISTICS: We used the Fisher exact test with 95% confidence intervals. RESULTS: We studied 587 patients and detected a total 24 adverse events, all of which have already been known during the licensing studies of the present vaccine. The frequencies of the adverse events were not different from what had been seen with the previously licensed 15 µg vaccine. CONCLUSIONS: Based on the results, the authors conclude that the new, reduced dose vaccine FluArt is safe and tolerable. Orv Hetil. 2017; 158(49): 1953-1959.

Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the "PEAPETT" study).

OBJECTIVE: Pulseless electrical activity (PEA) during cardiac arrest portends a poor prognosis. There is a paucity of data in the use of thrombolytic therapy in PEA and cardiopulmonary arrest due to confirmed pulmonary embolism (PE). We evaluated the outcome of low-dose systemic thrombolysis with tissue plasminogen activator (tPA) in patients presenting with PEA due to PE. METHODS: During a 34-month period, we treated 23 patients with PEA and cardiopulmonary arrest due to confirmed massive PE. All patients received 50 mg of tPA as intravenous push in 1 minute while cardiopulmonary resuscitation was ongoing. The time from initiation of cardiopulmonary resuscitation to administration of tPA was 6.5 ± 2.1 minutes. RESULTS: Return of spontaneous circulation occurred in 2 to 15 minutes after tPA administration in all but 1 patient. There was no minor or major bleeding despite chest compression. Of the 23 patients, 2 died in the hospital, and at 22 ± 3 months of follow-up, 20 patients (87%) were still alive. The right ventricular/left ventricular ratio and pulmonary artery systolic pressure dropped from 1.79 ± 0.27 and 58.10 ± 7.99 mm Hg on admission to 1.16 ± 0.13 and 40.25 ± 4.33 mm Hg within 48 hours, respectively (P< .001 for both comparisons). There was no recurrent venous thromboembolism or bleeding during hospitalization or at follow-up. CONCLUSION: Rapid administration of 50 mg of tPA is safe and effective in restoration of spontaneous circulation in PEA due to massive PE leading to enhanced survival and significant reduction in pulmonary artery pressures.

Transforming and simplifying the treatment of pulmonary embolism: "safe dose" thrombolysis plus new oral anticoagulants.

BACKGROUND: Administration of systemic thrombolysis in pulmonary embolism (PE) has been limited to severe forms due to the risk of intracerebral hemorrhage (ICH). There is growing evidence from small studies that low-dose systemic thrombolysis has equal efficacy to standard dose, while eliminating the risk of ICH. Little data exists on the combined use of low-dose systemic thrombolysis and new oral anticoagulants (NOAC). We evaluated the clinical and echocardiographic outcome of patients treated with low or "safe dose" thrombolysis (SDT) and NOAC at intermediate term. METHODS: We retrospectively identified 159 patients with massive and submassive PE who were treated with SDT and NOAC over a 2-year period by our group. They were followed prospectively for PE-related mortality, recurrent PE, bleeding, change in right/left ventricle (RV/LV) size, pulmonary artery systolic pressure (PASP), and clinical improvement at a mean follow-up of 18 ± 3 months. RESULTS: At 6 months, the RV/LV size was reduced from 1.29 ± 0.28 to 0.89 ± 0.03 (p < 0.001). The PASP dropped from 53.12 ± 3.85 mmHg to 30.39 ± 3.93 mmHg (p < 0.001). There was no ICH or in-hospital major or minor bleeding. At 18 months, three patients died of cancer. Recurrent PE developed in one patient who had been later switched to warfarin. The duration of hospitalization was 1.8 ± 0.3 days. CONCLUSION: With combination of SDT and NOAC, treatment of massive and submassive PE becomes identical and is transformed from an "anticoagulation first" to a "thrombolysis first" approach, thereby making treatment streamlined, simple, safe and effective, accessible and inexpensive.

Evaluation of Vaccine Immunogenicity-Correlates to Real-World Protection: Influenza.

Recent events highlighted that, despite decades of studying vaccine immunogenicity and efforts toward finding correlates of protection, evaluating real-world vaccine efficacy as well as establishing meaningful licensing criteria still represents a significant challenge. In this paper, we review all aspects of influenza vaccine immunogenicity, including animal and human challenge studies, humoral and cellular immunity parameters, and their potential correlation with real-life protection from disease.

Protection of Chinese painted quails (Coturnix chinensis) against a highly pathogenic H5N1 avian influenza virus strain after vaccination.

Chinese painted quails immunized with a single dose (6 µg HA) of inactivated H5N1 (clade 1) influenza vaccine NIBRG-14 and challenged with 100 LD50 of the heterologous A/Swan/Nagybaracska/01/06(H5N1) (clade 2.2) strain were protected, whereas unvaccinated quails died after challenge. No viral antigens or RNA were detected in cloacal swabs from immunized animals. Sera obtained post-immunization gave low titres in serological assays against the vaccine and the challenge viruses. Our results demonstrate the protective efficacy of the NIBRG-14 strain against the challenge virus and the usefulness of these small birds in protection studies of influenza vaccines.

Developing Immunity Testing for SARS-CoV-2 and Other Novel Vaccines-Correlates of Immunogenicity Parameters with Protection.

During the assessment and licensing of novel vaccines, as well as post licensure follow up, it is critical to have reliable immunogenicity testing methods that relate well to real life protection [...].

Extinction of the Influenza B Yamagata Line during the COVID Pandemic-Implications for Vaccine Composition.

Vaccination remains the most effective way to mitigate the enormous burden of influenza on the health care system [...].

Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009-10 influenza season: a multicentre, randomised controlled trial.

BACKGROUND: With the ongoing 2009 pandemic of influenza A H1N1, development of pandemic influenza vaccines has generated much interest. We investigated the safety and immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1 vaccine in adult and elderly volunteers, given without or simultaneously with the 2009-10 seasonal trivalent influenza vaccine. METHODS: This prospective, randomised study was undertaken in two centres in Hungary. 355 participants, including 203 adults (18-60 years) and 152 elderly people (>60 years), were assigned by stratified randomisation to either 0.5 mL of the pandemic vaccine (Fluval P, a monovalent vaccine with 6 microg haemagglutinin per 0.5 mL content and aluminium phosphate gel adjuvant; n=178) or 0.5 mL of the pandemic vaccine and 0.5 mL of the seasonal trivalent vaccine (Fluval AB, a trivalent inactivated whole-virion influenza vaccine; n=177). All vaccinations were done by specific study personnel, who did not take part in the assessment of safety or immunogenicity. Co-primary objectives were safety and immunogenicity by haemagglutinin inhibition testing. All analyses were done according to a pre-established analysis plan. This study is registered with ClinicalTrials.gov, number NCT01010893. FINDINGS: Two participants receiving the pandemic vaccine only (group 1) and one receiving pandemic and seasonal vaccines (group 2) were lost to follow-up. Participants in both groups developed antibody responses against the pandemic influenza A H1N1 virus (group 1: seroconversion for adults 74.3%, 95% CI 64-6-82.4 and for elderly people 61.3%, 49.1-72.4; group 2: 76.8%, 67.2-84.7 and 81.8%, 71.4-89.7, respectively). Single doses of 6 microg fulfilled European Union and US licensing criteria for interpandemic and pandemic influenza vaccines. Simultaneously, participants in group 2 developed the immune responses needed for licensing for all three seasonal strains in the seasonal vaccine for the 2009-10 season. All adverse events were rare, mild, and transient; the most frequent were pain at injection site (eight cases in group 1 vs 18 in group 2) and fatigue for 1-2 days after vaccination (three vs five cases). INTERPRETATION: The present pandemic vaccine is safe and immunogenic in healthy adult and elderly patients, and needs low doses and only one injection to trigger immune responses to comply with licensing criteria. It can be safely co-administered with the 2009-10 seasonal influenza vaccine. FUNDING: Omninvest, Hungary.

A single-dose influenza A (H5N1) vaccine safe and immunogenic in adult and elderly patients: an approach to pandemic vaccine development.

With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic vaccines. Here we report a randomized multicenter dose-finding clinical trial of a whole-virion, inactivated, adjuvanted H5N1 vaccine in adult and elderly volunteers. Four hundred eighty patients were randomly assigned to receive one or two doses of 3.5 microg of the vaccine or one dose of 6 or 12 microg. The subjects were monitored for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition and microneutralization tests. The subjects developed antibody responses against the influenza A (H5N1) virus. Single doses of > or = 6 microg fulfilled EU and U.S. licensing criteria for interpandemic and pandemic influenza vaccines. Except for occasional injection site pain, malaise, and fever, no adverse events were observed. We found that the present vaccine is safe and immunogenic in healthy adult and elderly subjects and requires low doses and, unlike any other H5N1 vaccines, only one injection to trigger immune responses which comply with licensing criteria. A vaccine using the same methods as those described in this report, but based on a wild-type swine-origin 2009 (H1N1) influenza A virus isolate from the United States (supplied by the CDC), has been developed and is currently being tested by our group.

A Reduced Dose Whole Virion Aluminum Adjuvanted Seasonal Influenza Vaccine Is Immunogenic, Safe, and Well Tolerated in Pediatric Patients.

BACKGROUND: Data suggest that pediatric patients might react differently to influenza vaccination, both in terms of immunity and side effects. We have recently shown that using a whole virion vaccine with aluminum phosphate adjuvants, reduced dose vaccines containing 6 µg of viral hemagglutinin (HA) per strain are immunogenic, and well tolerated in adult and elderly patients. Here we show the results of a multicenter clinical trial of pediatric patients, using reduced doses of a new, whole virion, aluminum phosphate adjuvanted vaccine (FluArt, Budapest, Hungary). METHODS: A total of 120 healthy volunteers were included in two age groups (3-11 years, receiving 3 µg of HA per strain, and 12-18 years, receiving 6 µg of HA per strain). We used hemagglutination inhibition testing to assess immunogenicity, based on EMA and FDA licensing criteria, including post/pre-vaccination geometric mean titer ratios, seroconversion and seropositivity rates. Safety and tolerability were assessed using CHMP guidelines. RESULTS: All subjects entered the study and were vaccinated (ITT population). All 120 subjects attended the control visit on Day 21 (PP population). All immunogenicity licensing criteria were met in both age groups for all three vaccine virus strains. No serious adverse events were detected and the vaccine was well tolerated by both age groups. DISCUSSION: Using a whole virion vaccine and aluminum phosphate adjuvants, a reduction in the amount of the viral hemmaglutinin is possible while maintaining immunogenicity, safety and tolerability in pediatric and adolescent patients.

Cardiovascular risk status and primary prevention in postmenopausal women: the MENOCARD study.

OBJECTIVE: Our aim was to evaluate the usefulness of screening for cardiovascular risk factors and the effect of applying professional guidelines for risk reduction in postmenopausal women, as judged by the Framingham and the high-risk systematic coronary risk evaluation (SCORE) methods. METHODS: 18 menopause clinics in Hungary participated in the study, enrolling a total of 2789 patients. Physicians were asked to follow professional guidelines for the primary prevention of cardiovascular disease. Patients were requested to attend follow-up every four months for 12 months. RESULTS: The mean age of the patients was 56.7+/-6.9 years, and the time elapsed since the last menstrual period was 9.2+/-7.2 years. Overall, 29.4% of patients attended at least one follow-up visit. At the initial visit, high total cholesterol level (>5 mmol/l) was detected in 78% of patients, high triglyceride level (>1.7 mmol/l) in 29%, high systolic and/or diastolic blood pressure (>140/90 mmHg) in 32%, fasting plasma glucose level>6.1 mmol/l in 15%. Increased waist circumference (>88 cm) was found in 85.8% of the patients; 18.3% of the patients smoked, which did not change. After 12 months, all laboratory parameters and the blood pressure had improved significantly. Both the Framingham and SCORE systems showed a significant improvement in the cardiovascular risk status, and the rate of metabolic syndrome had decreased significantly by the end of the study. CONCLUSIONS: Screening postmenopausal women for cardiovascular risk and the application of professional guidelines for primary prevention may significantly reduce the risk of coronary artery disease in this group. Patient compliance with follow-up visits needs improvement.

Licensing the first reduced, 6 µg dose whole virion, aluminum adjuvanted seasonal influenza vaccine - A randomized-controlled multicenter trial.

INTRODUCTION: Shortages of vaccine supplies repeatedly occur, limiting our abilities to prevent influenza. Therefore, increasing production volume remains a priority. The presently licensed seasonal influenza vaccines contain 15 µg of viral hemagglutinin per strain in adult, and up to 60 µg in elderly patients. Decreasing the amount of viral parts while maintaining efficacy is one way of increasing production capacity. METHODS: This was multicenter, stratified (18-60 years and >60 years of age), prospective, randomized, double-blind, active-controlled, parallel-arm, non-inferiority clinical trial, conducted in the European Union, involving 1206 patients. We used hemagglutination inhibition assay to assess the immunogenicity of a newly developed, whole virion, seasonal trivalent influenza vaccine, containing 6 µg hemagglutinin per strain (FluArt, Hungary) and to assess whether it is non-inferior to the presently licensed vaccine containing 15 µg hemagglutinin per strain. Safety and tolerability of both vaccines were assessed based on EMEA guidelines. RESULTS: The reduced dose vaccine containing 6 µg of hemagglutinin per strain was safe and non-inferior to the currently licensed 15 µg vaccine, not only in adult, but also in elderly patients, according to the immunogenicity criteria by the FDA and EMEA (seroconversion, seroprotection and post/pre vaccination GMT ratios), and it fulfilled all applicable licensing requirements for both age groups. CONCLUSIONS: Based on the results, the reduced dose vaccine was licensed in the EU member state Hungary and safely administered in over 1.5 million cases so far. The amount of viral hemagglutinin needed can be reduced by using a whole virion vaccine with aluminum phosphate adjuvants. REGISTRATION: This study was registered by the European Clinical Trials Database, EudraCT, number: 2011-003314-16.

Safety and immunogenicity of a prepandemic influenza A (H5N1) vaccine in children.

BACKGROUND: The avian influenza A (H5N1) virus is considered to be a potential cause of the next influenza pandemic. Children may be particularly vulnerable to the pandemic virus, and they may react differently than adults to vaccines. We report the results of the first clinical trial of an H5N1 vaccine in children. METHODS: Twelve healthy children (mean age +/- SD: 12.73 +/- 2.77 years) received a single dose of 6 microg of the inactivated whole virus vaccine Fluval. Twenty-one days after vaccination, immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Safety information was collected for 180 days. RESULTS: No side-effects were observed, and the vaccine fulfilled all applicable U.S. and European immunogenicity criteria for licensure. The post/prevaccination geometric mean titer ratio was 16.95, the rate of seroconversion was 75% and the rate of seroprotection was also 75% 21 days after vaccination. CONCLUSIONS: We confirmed our earlier findings of the present vaccine in adults showing encouraging safety and immunogenicity properties in children. Studies with the present vaccine in elderly subjects are underway.

[Our experience with the preparation of fixed segmented bridges with nonrigid extracoronally placed connectors. Case series]. / Extrakoronális csúztatóval kombinált osztott hidak készitésével szerzett tapasztalataink. Esetismertetés.

AIMS: For the replacement of dental deficiencies when the difference in axis between the future abutment teeth is considerable and preparation of a fixed bridge-prosthesis is planned without the sacrifice of too much extra dental tissue, one possibility is to prepare fixed separated dentures with nonrigid connectors. METHODS: From 1999 to 2007, we prepared such dentures, initially using intracoronal retainers in accordance with the literature, after that we positioned the retainers extracoronally whenever this was possible. RESULTS: In 35 cases we prepared multi-unit fixed prostheses with a total of 43 retainers. These segmented prostheses could be fixed rigidly after cementation. All of them remain in place without any complaint. CONCLUSION: Fixed dentures prepared with extracoronal retainers proved safe and esthetic and extra dental tissue is not sacrificed.

[Orthodontic and oral surgery therapy in cleidocranial dysplasia]. / Orthodontiai és szájsebészeti terápia cleidocranialis dysplasia esetében.

A cleidocranial dysplasia is an autosomal dominant inherited condition consisting of generalized skeletal disorder. Associated dental signs are present in 93,5%; failure of tooth eruption with multiple supernumerary teeth, dilaceration of roots, crown germination, microdontia, high arched palate, midface hypoplasia, high gonion angle. The molecular- genetic analysis revealed a missense mutation in the CBFA1 gene located on chromosome 6p21, which is considered to be etiological factor for CCD. Orthodontic and oral surgery therapy of a 13 year-old child with CCD was performed due to aesthetic and functional problems. The supernumerary germs were removed and the teeth were aligned with orthodontic appliances. Temporary functional rehabilitation was solved with partial denture. The presented case and the literature data support the importance of early diagnosis of CCD. The good collaboration of the orthodontic and maxillo-facial surgery specialists help achieve the correct rehabilitation of the patient.

Echocardiographic findings in patients with Williams-Beuren syndrome.

BACKGROUND: Williams-Beuren syndrome is a multisystem developmental disorder caused by a microdeletion at chromosome 7q11.23. In its classic form it includes dysmorphic facial features, joint contractures, retardation of growth and mental development, gregarious personality, visuospatial cognitive deficits, hypercalcemia, primary or secondary hypertension and cardiovascular disorders. AIM: Clinical diagnosis of Williams-Beuren syndrome can be a challenge in young patients if none of the characteristic cardiovascular features, i.e. supravalvular aortic stenosis or pulmonary artery stenosis, are present. Our aim was to demonstrate the changes in cardiovascular lesions during the postnatal development of Williams-Beuren patients and to follow all cardiovascular findings beyond the most common ones. METHODS: The cardiovascular status of 29 patients with Williams-Beuren syndrome (mean age 12.8 years) was recorded in correlation with age. RESULTS: Cardiovascular diagnoses changed in the majority (72.4%) of patients. Interestingly, 44.8% of the patients had periods with no reported cardiovascular disease. Furthermore, 65.5% of the patients experienced periods when none of the typical cardiovascular lesions, i.e. diffuse or localized supravalvular aortic stenosis and/or pulmonary artery stenosis, were detected. Spontaneous regression and progression of both supravalvular aortic stenosis and pulmonary artery stenosis were observed. An unexpectedly high frequency (41%) of mitral valve disorders was found. CONCLUSIONS: Our study showed that temporary absence of and changes in cardiovascular findings are frequent in Williams-Beuren syndrome. These results could contribute to the refinement of diagnostic criteria and recommendations for cardiovascular follow-up of patients with this syndrome.

The role of dental evaluation and cephalometric analysis in the diagnosis of Williams-Beuren syndrome.

Williams-Beuren syndrome (WS) is a genetic condition with an incidence of 1 in 20,000-50,000 live births. The syndrome consists of supravalvular aortic stenosis, characteristic dysmorphic facial features named "elf face" and intellectual disability. Early diagnosis of the syndrome is important since many of its features require treatment, and the prognosis can be dramatically improved by early recognition and management. This developmental disorder is well known to be clinically heterogeneous, making diagnosis difficult if based on the clinical picture. However, genetic testing is expensive and it is not cost effective to screen all patients based on clinical suspicion. Our goal was to develop a novel clinical screening method that would be sensitive, specific, inexpensive and readily available. We performed cephalometric analysis and dental evaluation of 33 patients with genetically proven WS. Cephalometric analysis of soft tissues showed that with normal SNA, SNB and ANB angles, the lips were in front of the line of harmony. This finding was present in all WS patients (n = 33) but in none of the age-matched controls (n = 100). No other differences were found between WS and control patients. This cephalometric finding is specific and sensitive for WS and can be used in the diagnostic procedure, whereas none of the conventional dental evaluations are useful.

Estrogen replacement therapy reverses changes in intramural coronary resistance arteries caused by female sex hormone depletion.

OBJECTIVE: We tested the hypothesis that female sex hormone depletion and estradiol replacement therapy significantly influences the biomechanical properties of intramural coronary resistance arteries. DESIGN: Female rats (n=30) were divided into three groups. In group O, rats were subjected to bilateral ovariectomy. Group HRT was subjected to bilateral ovariectomy and estradiol replacement therapy. Rats in group C served as controls. One month after ovariectomy, intramural coronary arteries (approximately 200 microm in diameter) branching from the left anterior descending coronary were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased in steps between 0 and 90 mm Hg. The steady state diameter at each step was measured. These measurements were repeated in the presence of U46619, a thromboxane (TX) A2 receptor agonist (at a concentration of 10(-6) M), and bradykinin (BK; at 10(-6) M). Finally, Ca2+-free Krebs-induced passive diameter (PD) was measured in each group. RESULTS: Ovariectomy increased spontaneous myogenic tone of coronary arteries (p<0.05), which was normalized by estrogen replacement. Ovariectomy decreased distensibility observed at low pressure, although passive diameter was not changed. Estrogen replacement decreased wall stress and elastic modulus (p<0.05). The thromboxane A2 agonist induced the largest contraction in the ovariectomized group, whereas bradykinin-induced relaxation was the largest in the estrogen replacement group (p<0.05). CONCLUSION: Estradiol hormone replacement therapy (HRT) may exert a beneficial effect on myocardial perfusion in menopause by opposing the deterioration of biomechanical properties of intramural coronary resistance vessels induced by female sex hormone depletion.

New oral anticoagulants in the treatment of heparin-induced thrombocytopenia.

BACKGROUND: Heparin induced thrombocytopenia (HIT) is a potentially catastrophic syndrome with a high incidence of vascular thrombosis. There are little data on the efficacy of new oral anticoagulants (NOAC) in this setting. This study reports on the outcome of patients with HIT, treated with NOAC. MATERIALS AND METHODS: We retrospectively identified 22 patients with HIT who were treated by our group with a combination of NOAC and a short course of argatroban. These patients were evaluated in a prospective fashion for development of outcomes at a mean follow up of 19±3 months. RESULTS: There were a total of 5 deep and 2 superficial vein thromboses diagnosed at index hospitalization. No patient developed arterial thrombosis. All patients tolerated NOAC and their platelet count normalized before discharge. At 19 months of follow-up, 6 patients had died of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous thromboembolism in any patient. CONCLUSIONS: In patients with HIT, a short course of parenteral treatment with argatroban followed by administration of a NOAC is highly safe and effective in prevention of thrombosis and normalization of platelet count. Development of HIT however, portends a poor prognosis independent of vascular thrombosis.