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Article ; Online: Anakinra for the treatment of adult secondary HLH: a retrospective experience.

Naymagon, Leonard

2022 Volume 116, Issue 6, Page(s) 947–955

Abstract: Anti-cytokine therapies have been gaining attention as a means of improving outcomes in adult secondary HLH (asHLH), which currently has poor outcomes when treated with standard etoposide-based therapies. Anakinra is an interleukin-1 antagonist that is ... ...

Abstract	Anti-cytokine therapies have been gaining attention as a means of improving outcomes in adult secondary HLH (asHLH), which currently has poor outcomes when treated with standard etoposide-based therapies. Anakinra is an interleukin-1 antagonist that is increasingly being used in the management of asHLH. Here is described a multi-hospital series of 16 adult patients with secondary HLH treated with anakinra. Provoking factors of secondary HLH included hematologic malignancy (n = 7, 44%), bacterial infection (n = 7, 44%), viral infection (n = 5, 31%), rheumatologic disorder (n = 4, 25%), and unknown (n = 1, 6%). Five patients remained alive at time of last follow-up (OS = 31%). Median OS was 1.7 months from initiation of anakinra (range 0.2-59). OS among patients with rheumatologic causes of secondary HLH was 75%, whereas only 17% of patients with other provoking factors survived (p = 0.0293). Anakinra was well tolerated, with only 1 patient experiencing associated toxicity (grade 3 liver injury). Anakinra may be useful in the management of asHLH provoked by rheumatologic conditions, although its benefit in asHLH provoked by other factors may be limited.
MeSH term(s)	Adult ; Humans ; Interleukin 1 Receptor Antagonist Protein/adverse effects ; Retrospective Studies ; Lymphohistiocytosis, Hemophagocytic/etiology ; Hematologic Neoplasms/complications ; Arthritis, Rheumatoid/drug therapy
Chemical Substances	Interleukin 1 Receptor Antagonist Protein
Language	English
Publishing date	2022-08-10
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-022-03430-9
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Zs.A 269: Show issues

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Article ; Online: The Role of Hereditary Thrombophilia Testing in Management of First-Time Pulmonary Embolism.

Sohval, Sophie / Naymagon, Leonard

Heart, lung & circulation

2024 Volume 33, Issue 4, Page(s) 533–537

Abstract: Aim: Hereditary thrombophilia (HT) testing is frequently conducted during the evaluation of patients with pulmonary embolism (PE). However, the utility of routine HT testing in this setting is unclear. We sought to assess the association of HT with risk ...

Abstract	Aim: Hereditary thrombophilia (HT) testing is frequently conducted during the evaluation of patients with pulmonary embolism (PE). However, the utility of routine HT testing in this setting is unclear. We sought to assess the association of HT with risk of recurrent venous thromboembolism (VTE) following first-time PE. Methods: We conducted a multi-hospital retrospective study. Two hundred and ninety (290) patients with a first-time PE, who had been tested for HT, completed at least 3 months of therapeutic anticoagulation (AC), subsequently discontinued AC, and were followed for at least 36 months thereafter, were included. Results: HT was present in 48 of the 290 included patients (17%). Median follow-up after discontinuing AC was 61 months (interquartile range, 43-79 months). The overall recurrence rate of VTE during follow-up was 58 per 290 (20%). A total of 47 of 242 patients (19%) in the HT-absent group had a recurrent VTE, compared with 11 of 48 (22%) in the HT-present group. There was no significant difference in VTE-free survival between groups on Kaplan-Meier analysis; the hazard ratio (HR) for VTE recurrence for those with HT compared to those without (HR HT-present: HT-absent) was 1.240 (95% confidence interval [CI] 0.614-2.502; p=0.548). On multivariable analysis, HT was not associated with risk of recurrent VTE (HR 1.262; 95% CI 0.640-2.488), and the only variable associated with VTE recurrence was unprovoked PE (HR 2.954; 95% CI 1.64-5.314). Conclusions: These findings demonstrate that the presence of HT is not associated with the risk of recurrent VTE following first PE, and support limiting the use of HT testing among patients with first PE.
MeSH term(s)	Humans ; Pulmonary Embolism/diagnosis ; Thrombophilia/diagnosis ; Thrombophilia/genetics ; Thrombophilia/complications ; Female ; Male ; Retrospective Studies ; Middle Aged ; Follow-Up Studies ; Aged ; Anticoagulants/therapeutic use ; Anticoagulants/administration & dosage ; Risk Factors ; Recurrence ; Adult
Chemical Substances	Anticoagulants
Language	English
Publishing date	2024-03-07
Publishing country	Australia
Document type	Journal Article ; Multicenter Study
ZDB-ID	2020980-0
ISSN	1444-2892 ; 1443-9506
ISSN (online)	1444-2892
ISSN	1443-9506
DOI	10.1016/j.hlc.2023.12.020
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Zs.A 4988: Show issues

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Article ; Online: Venous thrombosis of the liver: current and emerging concepts in management.

Naymagon, Leonard

Translational research : the journal of laboratory and clinical medicine

2020 Volume 225, Page(s) 54–69

Abstract: Venous thrombosis within the hepatic vasculature is associated with a distinct array of risk factors, characteristics, and potential complication. As such, it entails unique management considerations and strategies relative to the more common categories ... ...

Abstract	Venous thrombosis within the hepatic vasculature is associated with a distinct array of risk factors, characteristics, and potential complication. As such, it entails unique management considerations and strategies relative to the more common categories of venous thromboembolic disease. Although broadly divided into thrombosis of the afferent vasculature (the portal venous system) and efferent vasculature (the hepatic venous system), presentations and management strategies within these groupings are heterogeneous. Management decisions are influenced by a variety of factors including the chronicity, extent, and etiology of thrombosis. In this review we examine both portal vein thrombosis and hepatic vein thrombosis (and the associated Budd-Chiari Syndrome). We consider those factors which most impact presentation and most influence treatment. In so doing, we see how the particulars of specific cases introduce nuance into clinical decisions. At the same time we attempt to organize our understanding of such cases to help facilitate a more systematic approach. Critically, we must recognize that although increasing evidence is emerging to help guide our management strategies, the available data remain limited and largely retrospective. Indeed, current paradigms are based largely on observational experiences and expert consensus. As new and more rigorous studies emerge, treatment strategies are likely to be continually refined, and paradigm shifts are sure to occur.
MeSH term(s)	Humans ; Liver Diseases/complications ; Portal Vein/pathology ; Venous Thrombosis/complications ; Venous Thrombosis/therapy
Language	English
Publishing date	2020-05-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2020.04.012
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Article ; Online: Can we truly diagnose adult secondary hemophagocytic lymphohistiocytosis (HLH)? A critical review of current paradigms.

Naymagon, Leonard

Pathology, research and practice

2020 Volume 218, Page(s) 153321

Abstract: The HLH-2004 criteria were initially conceived as inclusion criteria for a clinical trial investigating therapy for (largely primary) pediatric hemophagocytic lymphohistiocytosis (HLH). These criteria have since been extrapolated to diagnose adult ... ...

Abstract	The HLH-2004 criteria were initially conceived as inclusion criteria for a clinical trial investigating therapy for (largely primary) pediatric hemophagocytic lymphohistiocytosis (HLH). These criteria have since been extrapolated to diagnose adult secondary HLH despite their questionable generalizability. It remains unclear whether these diagnostic criteria are truly applicable among adult secondary cases, and rigorous evidence for their use among such patients is lacking. This review critically examines the utility of the HLH-2004 criteria for the diagnosis of adult secondary HLH. It is framed as a reappraisal of each of the criteria's individual components, with an assessment of the relevance of, and/or evidence regarding, each. There are clear limitations to these criteria as they apply to adult secondary HLH, however they may help guide our understanding of the disease to some extent. Some new paradigms are emerging for the diagnosis of adult secondary HLH, however these too are limited by the difficulties inherent in formulating specific criteria for a very non-specific syndrome, which lacks any single gold-standard diagnostic test.
MeSH term(s)	Age Factors ; Biomarkers/blood ; Diagnosis, Differential ; Fever/diagnosis ; Genetic Predisposition to Disease ; Humans ; Hypertriglyceridemia/diagnosis ; Lymphohistiocytosis, Hemophagocytic/blood ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/genetics ; Lymphohistiocytosis, Hemophagocytic/immunology ; Neutropenia/diagnosis ; Predictive Value of Tests ; Prognosis ; Reproducibility of Results ; Splenomegaly/diagnosis ; Thrombocytopenia/diagnosis
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-12-17
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2020.153321
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Article ; Online: Inflamed-HLH, MAS, or something else?

Kumar, Ashish / Cournoyer, Eily / Naymagon, Leonard

Hematology. American Society of Hematology. Education Program

2023 Volume 2023, Issue 1, Page(s) 31–36

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive and maladaptive inflammation. Primary HLH is most frequently encountered in young children, and, without timely recognition and therapy, can lead to multiorgan failure and death. It is ... ...

Abstract	Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive and maladaptive inflammation. Primary HLH is most frequently encountered in young children, and, without timely recognition and therapy, can lead to multiorgan failure and death. It is most often diagnosed using the HLH-2004 criteria and by identifying pathological mutations. However, the HLH-2004 criteria are not specific for HLH, and patients can easily fulfill these diagnostic criteria in other proinflammatory states in which HLH-therapy would not be indicated, including hematologic malignancies, infections, and rheumatologic disease. Therefore, great care must be taken to ensure that the specific disease associated with features of HLH is accurately recognized, as consequences of improper treatment can be catastrophic. We propose a diagnostic pathway for patients for whom HLH is on the differential (visual abstract). Importantly, in situations in which the initial diagnostic workup is equivocal or unrevealing, reevaluation for occult malignancy, infection, or rheumatologic disease would be prudent, as occult presentations may be missed on primary evaluation. Temporizing medications can be used in critically ill patients while awaiting secondary evaluation. By using this framework, clinicians will be able to more reliably discern primary HLH from other pro-inflammatory states and thus provide timely, appropriate disease-specific therapy.
MeSH term(s)	Child ; Humans ; Child, Preschool ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/genetics ; Lymphohistiocytosis, Hemophagocytic/therapy ; Multiple Organ Failure ; Syndrome ; Hematologic Neoplasms/complications ; Arthritis, Rheumatoid/complications
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2084287-9
ISSN	1520-4383 ; 1520-4391
ISSN (online)	1520-4383
ISSN	1520-4391
DOI	10.1182/hematology.2023000463
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Article ; Online: The utility of hereditary thrombophilia testing among patients with unprovoked venous thromboembolism.

Olivo Freites, Cristina / Naymagon, Leonard

International journal of laboratory hematology

2021 Volume 44, Issue 2, Page(s) 393–398

Abstract: Introduction: Hereditary-thrombophilia (HT) testing is often sent during the evaluation of patients with unprovoked venous thromboembolism (VTE). This remains a frequent practice even though the results of such testing are often of unclear practical ... ...

Abstract	Introduction: Hereditary-thrombophilia (HT) testing is often sent during the evaluation of patients with unprovoked venous thromboembolism (VTE). This remains a frequent practice even though the results of such testing are often of unclear practical significance. Methods: We conducted a multicenter retrospective study to assess whether HT is associated with risk of recurrent VTE among patients who discontinue anticoagulation (AC) following an unprovoked VTE. Results: A total of 528 adult patients were included, 28% of whom (N = 110) tested positive for HT. Median follow-up was 55 months (IQR 40-66 months) following AC discontinuation. One hundred and twenty-four patients (23%) had a recurrent VTE during follow-up, including 29/110 with HT (26%) and 95/418 without HT (23%). Risk of recurrent VTE over time was similar between the two groups (logrank P = .47). The HR for recurrence among patients with HT was 1.17 (95% CI 0.76 to 1.81). On multivariable analysis, HT was not associated with recurrence of VTE (HR with HT = 1.07 (95% CI 0.69-1.65), P = .74). The only factor significantly associated with risk of VTE recurrence on multivariable analysis was presence of PE (as opposed to DVT alone) (HR = 1.54, 95% CI 1.02-2.30, P = .035). Conclusion: The presence of HT was not associated with risk of recurrent VTE in this cohort of patients. These findings underscore the questionable clinical utility of routine thrombophilia testing among patient with unprovoked VTE and suggest that such testing should not be routinely pursued.
MeSH term(s)	Adult ; Anticoagulants ; Blood Coagulation ; Cohort Studies ; Humans ; Recurrence ; Retrospective Studies ; Risk Factors ; Thrombophilia/complications ; Thrombophilia/diagnosis ; Venous Thromboembolism/diagnosis
Chemical Substances	Anticoagulants
Language	English
Publishing date	2021-11-08
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.13752
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Article ; Online: Equivalent thrombotic risk with Warfarin, Dabigatran, or Enoxaparin after failure of initial direct oral anticoagulation (DOAC) therapy.

Shyu, Margaret / Liu, Angela / Srikureja, Anya / Gregorian, Alison / Srisuwananukorn, Andrew / Tremblay, Douglas / Naymagon, Leonard

Journal of thrombosis and thrombolysis

2024

Abstract: Background: The direct oral anticoagulants (DOACs) are now commonly regarded as first line anticoagulants in most cases of venous thromboembolism (VTE). However, the optimal choice of subsequent anticoagulant in instances of first line DOAC failure is ... ...

Abstract	Background: The direct oral anticoagulants (DOACs) are now commonly regarded as first line anticoagulants in most cases of venous thromboembolism (VTE). However, the optimal choice of subsequent anticoagulant in instances of first line DOAC failure is unclear. Objectives: To describe and compare outcomes with second line anticoagulants used after DOAC failure. Methods: Patients seen at an urban hospital system for an episode of acute VTE initially treated with either apixaban or rivaroxaban who experienced a subsequent recurrent thrombosis while on anticoagulation (1st recurrent thrombosis) were included. Results: In total, 166 patients after apixaban or rivaroxaban failure were included. Following DOAC failure (1st recurrent thrombosis), the subsequent anticoagulant was warfarin in 60 patients (36%), dabigatran in 42 patients (25%), and enoxaparin in 64 patients (39%). Enoxaparin was preferentially prescribed in patients with a malignancy-associated etiology for 1st recurrent thrombosis (p < 0.01). The median follow-up time in our cohort was 16 months. There was no difference in 2nd recurrent thrombosis-free survival (p = 0.72) or risk for major bleeding event (p = 0.30) among patients treated with dabigatran, warfarin, or enoxaparin. Conclusions: In this retrospective analysis of patients failing first line DOAC therapy, rates of 2nd recurrent thrombosis and bleeding did not differ among subsequently chosen anticoagulants. Our study provides evidence that the optimal 2nd anticoagulant is not clear, and the choice of 2nd anticoagulant should continue to balance patient preference, cost, and provider experience.
Language	English
Publishing date	2024-04-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-024-02978-z
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Article ; Online: Plasmodium falciparum-Induced Autoimmune Hemolytic Anemia in a Pregnant Patient with Sickle Cell Disease.

Rupani, Karishma Vijay / Waksal, Julian / Cytryn, Lawrence / Naymagon, Leonard

The American journal of case reports

2023 Volume 24, Page(s) e938854

Abstract: BACKGROUND Sickle cell disease (SCD) is an autosomal recessive hereditary condition characterized by chronic hemolytic anemia and painful vaso-occlusive episodes. Homozygous sickle cell patients are at increased risk of morbidity and mortality from ... ...

Abstract	BACKGROUND Sickle cell disease (SCD) is an autosomal recessive hereditary condition characterized by chronic hemolytic anemia and painful vaso-occlusive episodes. Homozygous sickle cell patients are at increased risk of morbidity and mortality from malaria. Autoimmune hemolytic anemia (AIHA) secondary to, or in the setting of, malarial infection is rare. In our case, the concurrence of Plasmodium falciparum malarial parasitemia and AIHA led to severe hemolytic anemia with an extensive packed red blood cell transfusion requirement. The patient's underlying SCD also contributed to the severity of the anemia and persistence of the malarial infection. CASE REPORT We report the case of a 29-year-old woman in the second trimester of pregnancy, with a history of SCD, who presented with severe anemia beyond her typical baseline in the setting of P. falciparum malaria. Hemolysis markers, including lactate dehydrogenase and bilirubin, were elevated. Direct Coombs testing was positive for IgG and C3 antibodies. Treatment with antimalarial agents and steroids led to clinical improvement and eventual clearance of the parasitemia. CONCLUSIONS Our patient's clinical course was most compatible with P. falciparum malaria-induced AIHA. Although she received a short course of steroids, it was treatment and clearance of the parasitemia that led to resolution of the hemolysis and a return to baseline hemoglobin levels. While the exact mechanism of AIHA in malaria is not well characterized, several unique mechanisms have been proposed and should be considered in cases of P. falciparum malaria manifesting with particularly severe hemolytic anemia.
MeSH term(s)	Pregnancy ; Female ; Humans ; Adult ; Anemia, Hemolytic, Autoimmune/diagnosis ; Anemia, Hemolytic, Autoimmune/therapy ; Anemia, Hemolytic, Autoimmune/complications ; Plasmodium falciparum ; Hemolysis ; Parasitemia/complications ; Anemia, Sickle Cell/complications ; Anemia, Sickle Cell/therapy ; Malaria, Falciparum/complications ; Malaria/complications ; Steroids/therapeutic use
Chemical Substances	Steroids
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2517183-5
ISSN	1941-5923 ; 1941-5923
ISSN (online)	1941-5923
ISSN	1941-5923
DOI	10.12659/AJCR.938854
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Article ; Online: Direct oral anticoagulants versus warfarin in patients with single antibody-positive anti-phospholipid syndrome.

Liu, Angela / Rupani, Karishma Vijay / Naymagon, Leonard

European journal of haematology

2022 Volume 109, Issue 1, Page(s) 69–74

Abstract: Background: The role of direct oral anticoagulants (DOACs) among patients with antiphospholipid syndrome (APLS) remains unclear. Warfarin has been shown to be superior to DOACs among high-risk APLS patients (particularly those with triple-positive APLS). ...

Abstract	Background: The role of direct oral anticoagulants (DOACs) among patients with antiphospholipid syndrome (APLS) remains unclear. Warfarin has been shown to be superior to DOACs among high-risk APLS patients (particularly those with triple-positive APLS). However, it remains unknown whether DOACs may be appropriate for lower-risk patients such as those with single-positive APLS. Methods: We conducted a retrospective study comparing the risk of recurrent thrombosis among single-positive APLS patients treated with DOACs (apixaban or rivaroxaban), and those treated with warfarin. Results: One-hundred-forty-three single-positive APLS patients, newly started on anticoagulation following a first thrombotic event, were included. Median follow-up was 54 months (IQR 29-73 months). Ninety-one patients (64%) received warfarin and 52 patients (36%) received a DOAC. Six patients (6.6%) who received warfarin experienced a recurrent thrombotic event compared with 3 of 52 (5.8%) patients who received a DOAC (p = .845). There was no difference in event-free survival between groups (HR DOAC:Warfarin = 0.952, 95% CI 0.232 - 3.908). Major bleeding was similar in both groups. Conclusions: These findings suggest that DOACs may be a safe and effective option for patients with single-positive APLS. Prospective studies are needed to confirm these findings.
MeSH term(s)	Administration, Oral ; Anticoagulants/adverse effects ; Antiphospholipid Syndrome/complications ; Antiphospholipid Syndrome/diagnosis ; Antiphospholipid Syndrome/drug therapy ; Humans ; Retrospective Studies ; Thrombosis/diagnosis ; Thrombosis/drug therapy ; Thrombosis/etiology ; Warfarin/adverse effects
Chemical Substances	Anticoagulants ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.13770
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Article ; Online: Utility of hereditary thrombophilia testing among patients with lower extremity deep vein thrombosis.

Liu, Angela / Phair, John / Naymagon, Leonard

Journal of vascular surgery. Venous and lymphatic disorders

2022 Volume 10, Issue 4, Page(s) 841–845

Abstract: Objective: Despite a growing consensus that testing for hereditary thrombophilia (HT) is not recommended in the setting of venous thromboembolism (VTE), such testing is still often requested. We evaluated the effects of HT on the risk of recurrent VTE ... ...

Abstract	Objective: Despite a growing consensus that testing for hereditary thrombophilia (HT) is not recommended in the setting of venous thromboembolism (VTE), such testing is still often requested. We evaluated the effects of HT on the risk of recurrent VTE for patients with lower extremity deep vein thrombosis (DVT). Methods: We conducted a multihospital retrospective study of 867 patients with first-time proximal lower extremity DVT who had undergone testing for HT. Patients with and without HT were compared regarding their VTE recurrence risk via Kaplan-Meier and multivariable analysis. Results: HT was present in 166 patients (19%). The baseline characteristics were similar between the patients with HT and without HT. No significant difference was found in the recurrence rates between the two groups (HT, 17%; no HT, 15%; P = .345). A Kaplan-Meier survival analysis revealed no significant differences in VTE-free survival between the patients with and without HT (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.77-1.84; P = .421). On multivariable analysis, the presence of HT was not associated with recurrent VTE. A higher body mass index (HR, 1.06; 95% CI, 1.03-1.10; P = .004) and unprovoked DVT (HR, 2.48; 95% CI, 1.69-3.66; P < .001) were risk factors for recurrence. Conclusions: HT had no significant impact on the recurrence risk for patients with first-time lower extremity DVT. HT test results would, thus, not be expected to change clinical management and should therefore not be requested routinely for patients with DVT.
MeSH term(s)	Anticoagulants ; Humans ; Lower Extremity ; Pulmonary Embolism ; Recurrence ; Retrospective Studies ; Risk Factors ; Thrombophilia/complications ; Thrombophilia/diagnosis ; Venous Thromboembolism/diagnosis ; Venous Thrombosis/diagnosis
Chemical Substances	Anticoagulants
Language	English
Publishing date	2022-03-26
Publishing country	United States
Document type	Journal Article
ISSN	2213-3348
ISSN (online)	2213-3348
DOI	10.1016/j.jvsv.2022.02.019
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